Clinical trial NCT04818229
Conditions: Autoimmune Diseases
Sponsor: Connect Biopharma Australia Pty Ltd
Start date: 2021-06-01; Completion date: 2022-03-30
Enrollment: 112 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will investigate the effects of therapeutic and supratherapeutic oral doses of CBP-307 on the QTc interval in healthy subjects.

Detailed description:
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female subjects.

Arms: arm 1: Therapeutic and supratherapeutic multiple oral doses of CBP-307. arm 2: Moxifloxacin (positive control for method validation) and Placebo oral administration. arm 3: Moxifloxacin (positive control for method validation) and Placebo oral administration.
Interventions: intervention 1: CBP-307 intervention 2: Placebo-matched CBP-307 intervention 3: Moxifloxacin (Avelox) intervention 4: Placebo-matched Moxifloxacin
Intervention descriptions: intervention 1: CBP-307 capsules oral administration. intervention 2: Placebo-matched CBP-307 capsules oral administration. intervention 3: Moxifloxacin tablets oral administration。 intervention 4: Placebo-matched Moxifloxacin tablets oral administration.

Protocol documents:
Prot_000.pdf: 
Clinical Study Report 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002  
 
16.1.1. 
Protocol and Amendments 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 1 of 11 
Summary of Amended Protocol Changes 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Protocol Amendment 4 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Protocol Amendment 2 Date: 03 August 2021 
Protocol Amendment 3 Date: 26 October 2021 
Protocol Amendment 4 Date: 12 January 2022 
Protocol Version: 5.0 
Investigational Medicinal Product: CBP-307 
Protocol Reference Number: CBP-307AU002 
Covance Study Number: 8463245 
IND Number: 134585 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Sites: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Clinical Pharmacology of Miami (CPMI), 
LLC 
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Sponsor Signatory: 
Ping Li, MD 
Principal Investigators: 
Nicholas Farinola, MBBS 
CMAX 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 
________________________________________ 
The primary changes implemented in this protocol amendment are due to a recent surge in 
Coronavirus Disease 2019 (COVID-19) cases at one of the clinical sites enrolling subjects in 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 2 of 11 
this study. Between Day -2 and Day 9 there were 21 subjects at the site who tested positive 
for COVID-19. To protect the safety of the subjects and site personnel, all 35 subjects at the 
site were discharged from the unit and were discontinued from the study following 
completion of the Early Termination assessments. Subjects will be monitored as outlined in 
the protocol. 
As a result of this outbreak, the protocol has been modified to allow time for the sites to 
perform additional COVID-19 tests and confirm results prior to enrolling the subjects in the 
study. The sites may bring in subjects for check-in on Day -4 rather than Day -2, if necessary. 
In addition, the number of subjects planned to be randomized in the study was increased from 
64 to 68 subjects to ensure an adequate number of evaluable subjects are randomized to meet 
the objectives of the study. 
Minor changes: 
1. The protocol version and date were updated throughout the protocol. 
2. Typographical errors and formatting errors were corrected, as necessary. 
3. List of abbreviations was revised, as necessary. 
A detailed summary of changes is presented below: 
Synopsis and Section 3.1, Overall Study Design paragraphs 3 and 7 (including Figure 1) 
Previously read:  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Figure 1: Study Schematic 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1
Day 2


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 3 of 11 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at 
least 25 hours prior to the administration of study treatments on Day 1 and continue through 
24 hours after the administration of study treatments on Days 1, 6, 15, and 16 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK 
analysis will be collected predose and at each postdose cardiodynamic ECG timepoint. 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Now reads:  
In this study, approximately 68 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Figure 1: Study Schematic 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
(or on Day -4 depending on the clinical site’s requirement for Coronavirus Disease 2019 
[COVID-19] testing) and will remain at the study site until discharge on Day 19. Treatment 
administration will occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all 
subjects will receive placebo on Day -1). Continuous cardiodynamic ECG monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 6, 15, 
and 16 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1
Day 2
*
*


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 4 of 11 
timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15. Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Section 7, Study Assessments and Procedures 
Previously read:  
This study includes a screening period (Day -28 to Day -3), a treatment period (Days -2 to 
19), and a follow-up period (Day 29 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2) 
or baseline (Day -1 predose) will only be considered exclusionary if judged applicable by the 
investigator. For confirmation of enrollment eligibility based on pulse rate, the pulse rate 
assessed by vital signs, rather than the 12-lead ECG, will be used. For all subjects, the 
screening, check-in, or baseline blood pressure, pulse rate, and respiratory rate may be 
repeated after 5 to 10 minutes if the initial reading is believed to be atypical for the subject. 
Now reads:  
This study includes a screening period (Day -28 to Day -3 [or Day -5 depending on the 
clinical site’s requirement for COVID-19 testing]), a treatment period (Days -2 [or Day -4] to 
19), and a follow-up period (Day 29 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2 or 
Day -4 depending on the clinical site’s requirement for COVID-19 testing) or baseline (Day -
1 predose) will only be considered exclusionary if judged applicable by the investigator. For 
confirmation of enrollment eligibility based on pulse rate, the pulse rate assessed by vital 
signs, rather than the 12-lead ECG, will be used. For all subjects, the screening, check-in, or 
baseline blood pressure, pulse rate, and respiratory rate may be repeated after 5 to 10 minutes 
if the initial reading is believed to be atypical for the subject. 
Synopsis, Number of Subjects; Section 5.1, Investigational Products; and Section 8.1, 
Determination of Sample Size 
Previously read:  
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Now reads:  
Approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Appendix 2, Clinical Laboratory Evaluations, Footnote b 
Previously read:  
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be 
performed at Check-in (on Day -2 depending on the clinical site’s requirements for 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 5 of 11 
Coronavirus Disease 2019 testing) and at the follow-up visit (on Day 29±2 days). A positive 
urine pregnancy test will be confirmed with a serum pregnancy test.  
Now reads: 
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be 
performed at check-in (on Day -4 or Day -2 depending on the clinical site’s requirements for 
Coronavirus Disease 2019 testing) and at the follow-up visit (on Day 29±2 days). A positive 
urine pregnancy test will be confirmed with a serum pregnancy test.  
Appendix 4, Contraception Guidance, last paragraph for female subjects 
Previously read:  
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2) until 90 days after the follow-up visit. 
Now reads: 
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2 or Day -4 depending on the clinical site’s requirement for COVID-19 testing) until 
90 days after the follow-up visit. 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 6 of 11 
Appendix 6, Schedule of Assessments 
Previously read:  
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3
-2
-1
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
Demographics 
X 
Medical history 
X 
Admission to clinical 
research unit1 
X 
Discharge from clinical 
research unit2  
X 
Randomization 
X 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height/weight/BMI 
X 
Physical exam 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
Clinical chemistry  
(including cholesterol panel 
tests) 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, or 
HCVAb 
X 
12-lead safety
electrocardiogram4,8
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 7 of 11 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Cardiac Telemetry 
Monitoring9 
 
 
 
X 
X 
X 
(Day 3) 
 
X 
 (Day 7) 
 
 
 
 
 
 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
 
 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Follicle -stimulating 
hormone test 
(postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBP-307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Moxifloxacin/placebo 
administration 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).  
2. Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19. 
3. Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 18, and 19): 
Prior to and 2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: Tympanic temperature, 
respiratory rate, and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to discharge, supine vital signs (tympanic 
temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): Tympanic temperature, respiratory rate, and supine pulse 
rate and blood pressure. 
4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before discharge on 
Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 8 of 11 
5.
Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1,
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. The ECG effects
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 (supratherapeutic
concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 16.
6.
Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 29±2 days). A positive urine
pregnancy test will be confirmed with a serum pregnancy test.
7.
Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16).
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15.
8.
Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 hour postdose, ±15 minutes for ECGs and vital
sign measurements at 2 hours postdose and ±5 minutes for PK sampling at 2 hours postdose, ±5 minutes for 3 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose,
and ±30 minutes for 12 to 24, 72, and 96 hours postdose.
9.
Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 12 hours
postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended if necessary. The
start and stop date and time of the telemetry monitoring will be recorded in the eCRF.
Now reads: 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3
(or -5 if
needed for 
COVID-19 
testing) 1 
-2
(or -4 if 
needed for 
COVID-19 
testing) 1 
-1
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
Demographics 
X 
Medical history 
X 
Admission to clinical 
research unit1 
X 
Discharge from clinical 
research unit2  
X 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 9 of 11 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3  
(or -5 if 
needed for 
COVID-19 
testing) 1 
-2  
(or -4 if 
needed for 
COVID-19 
testing) 1 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height/weight/BMI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematology 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Clinical chemistry  
(including cholesterol 
panel tests) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, 
or HCVAb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead safety 
electrocardiogram4,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Cardiac Telemetry 
Monitoring9 
 
 
 
X 
X 
X 
(Day 
3) 
 
X 
 (Day 7) 
 
 
 
 
 
 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
 
 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Follicle -stimulating 
hormone test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 10 of 11 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3  
(or -5 if 
needed for 
COVID-19 
testing) 1 
-2  
(or -4 if 
needed for 
COVID-19 
testing) 1 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
(postmenopausal females 
only) 
CBP-307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Moxifloxacin/placebo 
administration 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; COVID-19 = Coronavirus Disease 2019; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C 
virus antibodies; HIV = human immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 to 4 days before start of dosing on Day 1 (on Day -4 or Day -2 depending on the clinical site’s 
requirements for COVID-19 testing).  
2. Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19. 
3. Screening and Check-in:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 18, and 19): Prior to and 
2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: Tympanic temperature, respiratory rate, 
and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to discharge, supine vital signs (tympanic temperature, 
pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): Tympanic temperature, respiratory rate, and supine pulse rate and 
blood pressure. 
4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before discharge on 
Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before 
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1, 
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. The ECG effects 
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 (supratherapeutic 
concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 16. 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 11 of 11 
6. Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed at Check-in (Day -4 or Day -2) and at the follow-up visit (Day 29±2 
days). A positive urine pregnancy test will be confirmed with a serum pregnancy test. 
7. Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16). 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 hour postdose, ±15 minutes for ECGs and vital 
sign measurements at 2 hours postdose and ±5 minutes for PK sampling at 2 hours postdose, ±5 minutes for 3 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, 
and ±30 minutes for 12 to 24, 72, and 96 hours postdose. 
9. Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 12 hours 
postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended if necessary. The 
start and stop date and time of the telemetry monitoring will be recorded in the eCRF. 
 


TITLE PAGE 
Protocol 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, 
Placebo- and Positive-Controlled Study to Investigate the Effects of 
CBP-307 on the QTC Interval in Healthy Subjects 
Protocol Amendment 4 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Protocol Amendment 2 Date: 03 August 2021 
Protocol Amendment 3 Date: 26 October 2021 
Protocol Amendment 4 Date: 12 January 2022 
Protocol Version: 5.0 
Investigational Medicinal Product: CBP-307 
Protocol Reference Number: CBP-307AU002 
Labcorp Study Number: 8463245 
IND Number: 134585 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Sites: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Clinical Pharmacology of Miami (CPMI), 
LLC 
550 West 84th Street 
Hialeah, Florida 33014 
United States  
Sponsor Signatory: 
Ping Li, MD 
Principal Investigators: 
Nicholas Farinola, MBBS 
CMAX 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Study: 8463245  
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 2 of 67 
SPONSOR APPROVAL 
I have read the protocol and approve it: 
 
 
 
 
 
 
 
Ping Li, MD 
 
Date 
VP, Clinical Development Asia 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 3 of 67 
INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
Nicholas Farinola, MBBS 
Date 
Principal Investigator 
CMAX 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Study: 8463245  
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 4 of 67 
INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
 
 
 
 
 
 
 
Juan Carlos Rondon, MD, JD, CPI, FCLM  
Date 
Principal Investigator 
CPMI, LLC 
 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Study: 8463245  
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022  
Page 5 of 67 
STUDY IDENTIFICATION 
Sponsor 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu 215400 
China 
Sponsor’s Study Contact 
Max Meng, BS 
Project Manager 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Tel: +86 0512 5357 7866 
Email: yhmeng@connectpharm.com 
Sponsor’s Medical Contact 
Suni Valasseri, MD 
Labcorp Clinical Research Unit Limited. 
Maidenhead 
United Kingdom 
Tel: +44 (0) 113 301 3650 
Email: S.Valasseri @labcorp.com 
Study Sites  
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
 
CPMI, LLC  
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Principal Investigators 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 


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Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC  
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Tel: 1-305-817-2900 
Email: jrondon@ergclinical.com 
Clinical Laboratories  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 
 
Ecco Lab Group 
8370 West Flagler Street, Suite 216 
Miami, Florida 33144 
United States 
Tel:  1-305-220-3805 
Bioanalytical Laboratory 
Margaret Mathews 
Director  
Agilex Biolabs 
28 Dalgleish Street 
Thebarton, South Australia 5031 
Australia 
Statistician 
Wei Xiao, MS 
Labcorp Drug Development, Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 


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SYNOPSIS 
Study Title 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the pharmacokinetics (PK) of CBP-307 following administration of 
therapeutic and supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on heart rate (HR), PR and QRS intervals, and T-wave morphology. 
Study Design 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only serious 
adverse events (SAEs) will be reported. After placebo administration to all subjects on 
Day -1, all adverse events (AEs), whether volunteered, elicited, or noted upon physical 
examination, will be recorded throughout the study (ie, from Day -1 until the end of the 
study).  
In this study, approximately 68 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 


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Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
(or on Day -4 depending on the clinical site’s requirement for Coronavirus Disease 2019 
[COVID-19] testing) and will remain at the study site until discharge on Day 19. Treatment 
administration will occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all 
subjects will receive placebo on Day -1). Continuous cardiodynamic electrocardiogram 
(ECG) monitoring and recording will begin at least 25 hours prior to the administration of 
study treatments on Day 1 and continue through 24 hours after the administration of study 
treatments on Days 1, 6, 15, and 16 and at corresponding timepoints on the day before 
dosing, ie, Day -1. Blood samples for PK analysis will be collected predose and at each 
postdose cardiodynamic ECG timepoint. Additional PK samples will be collected at 72 and 
96 hours following dosing on Day 15. Subjects will return to the study site for a follow-up 
visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 


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sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
Number of Subjects 
Approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Diagnosis and Main Criteria for Inclusion 
Healthy male and female subjects aged between 18 and 60 years (inclusive) with a body mass 
index between 18.0 and 30.0 kg/m2 (inclusive). 
Investigational Medicinal Products, Dose, and Mode of Administration 
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 titrated to 0.1 mg on 
Day 2; oral capsule) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6; oral capsule) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15; oral capsule) 
• Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 


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• Moxifloxacin (400 mg; oral tablet). 
Duration of Subject Participation in the Study 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3 [or Day -5 depending on the 
clinical site’s requirement for COVID-19 testing]), 21+2 days for the in-house treatment 
period (Days -2 [or Day -4] to 19), and 10 ±2 days for follow-up (Day 29±2 days), in total 
approximately 59 days. 
Endpoints 
Electrocardiogram (Cardiodynamic): 
The primary cardiodynamic endpoint is the change-from-baseline QTcF (ΔQTcF). 
The secondary cardiodynamic endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
Pharmacokinetics: 
Blood samples will be collected for the analysis of plasma concentrations of CBP-307. The 
PK parameters of CBP-307 will be calculated using a model independent approach. The 
following PK parameter endpoints will be calculated: maximum observed concentration 
(Cmax), area under the concentration-time curve from time zero extrapolated to infinity 
(AUCinf), area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24), and time of the maximum observed concentration (tmax). Other noncompartmental 
parameters may be reported. 
Safety: 
Adverse events, clinical laboratory evaluations (hematology, clinical chemistry, urinalysis), 
12-lead ECGs, and vital signs measurements. 
Statistical Methods 
Cardiodynamic evaluation: 
The primary analysis will be based on concentration-QTc modeling of the relationship 
between plasma concentrations of CBP-307 and change-from-baseline QTcF (∆QTcF) with 


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the intent to exclude an effect of placebo-corrected ΔQTcF (ΔΔQTcF) > 10 msec at clinically 
relevant plasma levels. Placebo-corrected ΔHR, ΔPR, ΔQRS, and ∆QTcF (ΔΔHR, ΔΔPR, 
ΔΔQRS, and ∆∆QTcF) will also be evaluated at each postdosing timepoint ('by-timepoint' 
analysis). An analysis of categorical outliers will be performed for changes in HR, PR, QRS, 
QTcF, T-wave morphology, and U-wave presence. Assay sensitivity will be evaluated by 
concentration-QTc analysis of the effect on ∆ΔQTcF of moxifloxacin using a similar model 
as for the primary analysis. 
Pharmacokinetics: 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, standard deviation, median, 
minimum, maximum geometric mean, and geometric coefficient of variation) separately by 
cohort. Individual and mean plasma CBP-307 and moxifloxacin concentration versus time 
data will be tabulated and plotted by dose level. Graphical displays of PK data may be 
provided as well.  
Pharmacokinetic/electrocardiography analyses: 
The relationship between CBP-307 plasma concentrations and the change from ∆QTcF will 
be evaluated using a linear mixed-effects modeling approach. 
Safety: 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed. 


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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SPONSOR APPROVAL ...........................................................................................................2 
INVESTIGATOR AGREEMENT.............................................................................................3 
INVESTIGATOR AGREEMENT.............................................................................................4 
STUDY IDENTIFICATION .....................................................................................................5 
SYNOPSIS .................................................................................................................................7 
TABLE OF CONTENTS .........................................................................................................12 
LIST OF TABLES AND FIGURES........................................................................................15 
LIST OF ABBREVIATIONS ..................................................................................................16 
1. 
INTRODUCTION ...........................................................................................................18 
1.1. 
Disease Background...............................................................................................18 
1.2. 
Overview of CBP-307............................................................................................18 
1.2.1. 
Summary of Clinical Experience .................................................................18 
1.2.1.1. 
Safety .................................................................................................19 
1.2.1.2. 
Pharmacokinetics ...............................................................................21 
1.3. 
Overview of Moxifloxacin .....................................................................................22 
1.4. 
Study Rationale ......................................................................................................22 
1.5. 
Benefit-risk Assessment.........................................................................................23 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................23 
2.1. 
Objectives ..............................................................................................................23 
2.2. 
Endpoints ...............................................................................................................23 
2.2.1. 
Electrocardiogram Endpoints .......................................................................23 
2.2.1.1. 
Primary ...............................................................................................23 
2.2.1.2. 
Secondary ...........................................................................................23 
2.2.2. 
Pharmacokinetic Endpoints .........................................................................24 
2.2.3. 
Safety Endpoints ..........................................................................................24 
3. 
INVESTIGATIONAL PLAN ..........................................................................................24 
3.1. 
Overall Study Design and Plan ..............................................................................24 
3.2. 
Discussion of Study Design ...................................................................................27 
3.3. 
Selection of Doses in the Study .............................................................................27 
4. 
SELECTION OF STUDY POPULATION .....................................................................28 
4.1. 
Inclusion Criteria ...................................................................................................28 
4.2. 
Exclusion Criteria ..................................................................................................29 
4.3. 
Subject Number and Identification ........................................................................31 
4.4. 
Subject Withdrawal and Replacement ...................................................................31 
4.5. 
Study Termination .................................................................................................32 
5. 
STUDY TREATMENTS .................................................................................................32 
5.1. 
Investigational Products .........................................................................................32 


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5.2. 
Study Treatment Administration............................................................................34 
5.3. 
Randomization .......................................................................................................34 
5.4. 
Blinding..................................................................................................................35 
5.5. 
Treatment Compliance ...........................................................................................35 
5.6. 
Drug Accountability...............................................................................................35 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................36 
6.1. 
Concomitant Therapies ..........................................................................................36 
6.2. 
Diet .........................................................................................................................36 
6.3. 
Smoking .................................................................................................................37 
6.4. 
Exercise ..................................................................................................................37 
6.5. 
Blood Donation ......................................................................................................37 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................37 
7.1. 
General Assessments .............................................................................................38 
7.1.1. 
Demographics ..............................................................................................38 
7.1.2. 
Medical History ...........................................................................................38 
7.2. 
Electrocardiography Assessments .........................................................................38 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording ......................................38 
7.2.1.1. 
TQT Plus Extraction Technique ........................................................38 
7.2.1.2. 
Expert Precision QT Analysis ............................................................39 
7.2.2. 
Safety 12-lead Electrocardiogram ................................................................39 
7.2.3. 
Cardiac Telemetry Monitoring ....................................................................40 
7.3. 
Pharmacokinetic Assessments ...............................................................................40 
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................40 
7.3.2. 
Analytical Methodology ..............................................................................40 
7.4. 
Safety and Tolerability Assessments .....................................................................40 
7.4.1. 
Adverse Events ............................................................................................40 
7.4.2. 
Clinical Laboratory Evaluations ..................................................................41 
7.4.3. 
Vital Signs ....................................................................................................41 
7.4.4. 
Physical Examination...................................................................................41 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................42 
8.1. 
Determination of Sample Size ...............................................................................42 
8.2. 
Analysis Populations ..............................................................................................43 
8.2.1. 
Cardiodynamic Population...........................................................................43 
8.2.2. 
Pharmacokinetic Population ........................................................................43 
8.2.3. 
Safety Population .........................................................................................43 
8.3. 
Cardiodynamic ECG Analyses ..............................................................................43 
8.4. 
Pharmacokinetic Analyses .....................................................................................47 
8.5. 
Safety Analysis ......................................................................................................47 
8.6. 
Interim Analysis .....................................................................................................47 


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9. 
REFERENCES ................................................................................................................48 
10. APPENDICES .................................................................................................................49 
Appendix 1: Adverse Event Reporting ..............................................................................50 
Appendix 2: Clinical Laboratory Evaluations ...................................................................55 
Appendix 3: Total Blood Volume......................................................................................56 
Appendix 4: Contraception Guidance ................................................................................57 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations ............................60 
Appendix 6: Schedule of Assessments ..............................................................................64 
 


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LIST OF TABLES AND FIGURES 
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................21 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................22 
Table 3: Study Treatments .................................................................................................33 
 
Figure 1: Study Schematic .................................................................................................25 
 


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LIST OF ABBREVIATIONS 
Abbreviation Definition 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUCinf 
area under the concentration-time curve from time zero extrapolated to 
infinity 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours 
postdose 
CI 
confidence interval 
CL/F 
apparent total clearance 
Cmax 
maximum observed concentration 
COVID-19 
Coronavirus Disease 2019 
CRO 
contract research organization 
CYP 
cytochrome P450 
Δ 
change-from-baseline 
ΔΔ 
placebo-corrected or placebo-adjusted change-from-baseline 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
HR 
heart rate 
HREC 
human resource ethics committee 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
IP 
investigational product 
IRB 
institutional review board 
LOESS 
locally estimated scatterplot smoothing 
LS 
least squares 
PK 
pharmacokinetic(s) 
PD 
pharmacodynamic(s) 
QD 
once daily 
QTc 
heart-corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 


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SAE 
serious adverse event 
SD 
standard deviation 
SE 
standard error 
S1P1 
sphingosine-1-phosphate receptor 1 
TEAE 
treatment-emergent adverse event(s) 
t1/2 
apparent terminal elimination half-life 
tmax 
time of the maximum observed concentration 
TQT 
thorough QT 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
λZ 
apparent terminal elimination rate constant 
 
 


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1. INTRODUCTION 
Refer to the investigator’s brochure (IB)1 for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile 
of the investigational medicinal product (IMP). 
1.1. 
Disease Background 
Autoimmune diseases are serious disorders that afflict a large portion of the world 
population; most have no cures. Significant advances have been made in the development of 
novel and disease-modifying therapies, but many of these new treatments have significant 
side effects. Treatments are needed that provide better risk-to-benefit profiles than the 
existing therapeutic choices. 
T cells are important immune cells that mediate the development of autoimmune disorders. 
Migration of T cells from lymphoid tissues to the sites of inflammation is central to the 
functions of T cells, and this process is dependent on sphingosine-1-phosphate (S1P) receptor 
1 (S1P1) which is known to ameliorate a variety of autoimmune diseases in animals and 
humans. Down modulation of this receptor, using S1P1 agonists, prevents T cell egress and 
results in a reduced number of circulating lymphocytes, particularly the CD4+- and CD8+-
naïve and central-memory T cell subsets.  
1.2. 
Overview of CBP-307 
CBP-307 is an S1P1 agonist that is being developed as a treatment for autoimmune diseases 
by Suzhou Connect Biopharmaceuticals, Ltd. CBP-307 (1-(2-fluoro-4-(5-(4-isobutylphenyl)-
1,2,4-oxadiazol-3-yl) benzyl) azetidine-3-carboxylic acid hemihydrate) is a potent, selective, 
small-molecule agonist of S1P1 and S1P5 receptors. Cell-based assays have confirmed 
CBP-307 induces internalization of S1P1 from the cell surface. This is consistent with the 
known mechanism of action of other S1P1 agonists, in that they down-modulate S1P1 and 
inhibit lymphocyte egress from lymphoid tissues.  
1.2.1. 
Summary of Clinical Experience 
The Phase 1 development of CBP-307 comprised 2 completed studies in healthy subjects: 
• A single and multiple ascending dose study to evaluate the safety and tolerability of 
CBP-307 including pharmacokinetic (PK), pharmacodynamic (PD), and food-effect 
assessments (Study CBP-307AU001) 
• A single-dose and multiple-dose, and fixed-dose titration study to evaluate the safety 
and tolerability of CBP-307 including PK and PD (Study CBP-307CN001) 
Currently, CBP-307 is being evaluated in 2 Phase 2 studies:  
• Ongoing multicenter study in subjects with moderate to severe ulcerative colitis 
(Study CBP-307CN002) to compare the clinical efficacy by evaluating the clinical 
response to CBP-307 versus placebo and the clinical remission and mucosal healing 


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achieved by CBP-307 versus placebo and to compare the clinical safety and 
tolerability of CBP-307 with those of placebo. 
• Ongoing study in subjects with moderate to severe Crohn’s disease compares clinical 
efficacy by evaluating the clinical response to CBP-307 versus placebo and the 
clinical remission and mucosal healing achieved by CBP-307 versus placebo and to 
compare the clinical safety and tolerability of CBP-307 with those of placebo. 
1.2.1.1. 
Safety 
Study CBP-307AU001 
A total of 44 healthy subjects were enrolled in the study. There were 28 subjects evaluated 
using the single-dose regimen (0.1, 0.25, 0.5, and 2.5 mg CBP-307) of which 21 subjects 
received CBP-307 and 7 subjects received placebo. Another 16 healthy subjects were 
evaluated using the multiple-dose regimen (0.15 and 0.25 mg CBP-307 given once daily 
[QD] for 28 consecutive days) of which 12 subjects received CBP-307 and 4 subjects 
received placebo. 
Overall, no unexpected safety signals were identified and no deaths occurred in this study. 
For the single-dose regiment, no subjects were discontinued due to a treatment-emergent AE 
(TEAE). In the multiple-dose regimen, there were 2 subjects who were discontinued from the 
study (due to increased alanine transaminase and second degree AV block [not considered to 
be clinically significant, as judged by the investigator]). All TEAEs resolved by the end of 
the study. 
In the single-dose regimen groups, TEAEs were reported in 12 of 21 subjects (57.1%) treated 
with CBP-307 and in 3 of 7 subjects (42.8%) treated with placebo. Most (91.7%) of the 
TEAEs in these subjects were mild in severity. The most common TEAEs in the 
CBP-307-treated groups were headache (28.6%); dizziness (19.0%); and bradycardia (9.5%). 
Bradycardia was reported only in 2 subjects receiving the highest (2.5 mg) CBP-307 dose. 
One subject had a serious adverse event (SAE) of bradycardia (associated with transient 
asystole) following a single dose of 2.5 mg CBP-307. 
In the multiple-dose regimen groups, CBP-307 at doses of 0.15 and 0.25 mg QD was 
generally well tolerated over the 28 days of dosing. Treatment-emergent AEs were reported 
in 11 of 12 subjects (91.7%) in the CBP-307 groups and 2 of 4 subjects (50.0%) in the 
placebo groups. Most (83.3%) TEAEs were mild in severity. The most common TEAEs in 
the 2 CBP-307 groups were headache (50.0%), and fatigue, nausea, and musculoskeletal pain 
(16.7% each). The incidences of these TEAEs were similar in both CBP-307-treated groups. 
No SAEs were reported for subjects in the multiple-dose regimen. 
Study CBP-307CN001 
A total of 30 eligible subjects completed 3 CBP-307 dose groups in ascending order of dose 
after randomization (in a ratio of 1:1:1): Group A (0.1 mg), Group B (0.2 mg), and Group C 
(0.3 mg). Each dose group consisted of 10 subjects, including 8 subjects receiving the 
investigational drug and 2 subjects receiving placebo by random assignment. The 
administration started from the dose of 0.1 mg. The subjects in this group received a single 


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dose of CBP-307 or placebo and were followed up for safety and tolerance within the next 
7 days. Then the subjects received 0.1 mg CBP-307 or placebo QD for 14 consecutive days 
and were followed up for safety and tolerance within the next 7 days. Dose escalation did not 
occur until the review of the single-dose regimen safety data from the 6 subjects in the 
previous dose cohort, and the safety data did not meet the termination criteria. The subjects in 
the dose of 0.3 mg received fixed-dose titration regimen, ie, 0.05 mg CBP-307 or placebo QD 
for 3 consecutive days; 0.1 mg CBP-307 or placebo QD for 2 consecutive days; 0.2 mg 
CBP-307 or placebo QD for 2 consecutive days; finally, 0.3 mg CBP-307 or placebo QD for 
14 consecutive days, and the subjects were followed up for safety and tolerance within the 
next 7 days. 
Overall, no unexpected safety signals were identified, and there were no deaths, SAEs, or 
AEs leading to the subject’s early withdrawal from the study after administration of 
CBP-307. In the safety set, a total of 29 subjects (8 in Group A, 100%; 8 in Group B, 100%; 
8 in Group C, 100% and 5 in placebo group, 83.3%) experienced TEAEs. 
During the single-dose period, a total of 14 subjects (5 of 8 in Group A, 62.5%; 6 of 8 in 
Group B, 75%, and 3 of 4 in placebo group, 75%) developed AEs. The incidence of TEAEs 
in Group A was generally similar to the placebo group. Among TEAEs in Group B, the 
incidence of AEs related to abnormalities in investigations was higher than that in placebo 
group, including lymphocyte count decreased (12.5%), white blood cell (WBC) count 
decreased (12.5%), neutrophil count decreased (12.5%), alanine aminotransferase increased 
(25%), and gamma-glutamyltransferase increased (12.5%), and aspartate aminotransferase 
increased (12.5%). Additionally, 1 subject experienced heart rate (HR) decreased (12.5%). 
During dose-titration period, 2 subjects (2 of 8 in Group C, 25%) experienced TEAEs. The 
TEAEs reported in Group C during the titration period included cough (12.5%) and increased 
upper airway secretion (12.5%). There were no TEAEs in the placebo group during this 
period. 
During repeated-dose period, a total of 28 subjects (8 of 8 in Group A, 100%; 8 of 8 in Group 
B, 100%; 8 of 8 in Group C, 100%; and 4 of 6 in placebo group, 66.7%) experienced AEs. 
The most frequent TEAE in Group A was upper respiratory tract infection (37.5%) compared 
with placebo group; the most frequent TEAEs in Group B and Group C included decreased 
lymphocyte count (Group B, 87.5%; Group C, 100.0%), WBC count (Group B, 87.5%; 
Group C, 62.5%), and neutrophil count (Group B, 50%; Group C, 12.5%). The TEAEs noted 
in Group B during the repeated-dose period also included increased alanine aminotransferase 
(25%), gamma-glutamyltransferase (37.5%), and aspartate aminotransferase (12.5%), upper 
respiratory tract infection (12.5%), influenza (12.5%), chest pain (12.5%), lethargy (25%), 
and neck pain (12.5%); TEAEs in Group C during the repeated-dose period also included 
increased alanine aminotransferase (25%), decreased HR (12.5%), and mouth ulcer (12.5%); 
the TEAEs in placebo group included increased transaminase (16.7%), prolonged activated 
partial thromboplastin time (1/6, 16.7%), decreased hemoglobin (16.7%), upper respiratory 
tract infection (16.7%), diarrhea (16.7%), dizziness (16.7%), and palpitations (16.7%). 
Study CBP-307CN002 
This study is ongoing and there are no safety data available.  


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Study CBP-307CN003 
This study is ongoing and there are no safety data available.  
1.2.1.2. 
Pharmacokinetics 
CBP-307 given orally as a single dose was readily absorbed; drug concentrations peaked at 
approximately 6 hours after administration, with an elimination apparent terminal elimination 
half-life (t1/2) of approximately 25 hours (range of 23 to 29 hours). The time to maximum 
observed concentration (Cmax) in the blood was delayed from 6 hours to approximately 
10 hours when CBP-307 was given with a high-fat diet. Food consumption also increased 
exposure (Table 1). 
For the single-dose administration, CBP-307 exposure (based on Cmax and area under the 
concentration-time curve [AUCs]) increased with increasing dose following a single-dose 
administration (Table 1).  
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Single-Dose 
Regimen PK 
Parameters 
Mean CBP-307 Single Dose ± SEM (n) 
0.1 mg 
0.25 mg 
0.5 mg 
(fasted) 
0.5 mg (fed)a 
2.5 mg 
AUClast 
(ng*h/mL) 
13.4 ± 3.54 
(n = 6) 
45.1 ± 5.25 
(n = 6) 
160 ± 22.8 
(n = 6) 
290 ± 28.1 
(n = 6) 
550 ± 96.3 
(n = 3) 
AUCinf 
(ng*h/mL) 
ND 
63.7 ± 2.14 
(n = 3) 
214 ± 58.3 
(n = 3) 
355 ± 44.3 
(n = 5) 
710 ± 164 
(n = 2) 
Cmax 
(ng/mL) 
0.537 ± 0.0931 
(n = 6) 
1.53 ± 
0.0935 
(n = 6) 
4.84 ± 0.706 
(n = 6) 
8.58 ± 1.11 
(n = 6) 
19.0 ± 3.55 
(n = 3) 
tmax 
(hours) 
7.33 ± 1.33 
(n = 6) 
5.33 ± 0.99 
(n = 6) 
5.00 ± 0.86 
(n = 6) 
10.67 ± 2.72 
(n = 6) 
6.00 ± 2.00 
(n = 3) 
t1/2 
(hours) 
ND 
23.3 ± 1.70 
(n = 3) 
28.8 ± 1.28 
(n = 3) 
26.0 ± 1.17 
(n = 5) 
22.8 ± 3.96 
(n = 2) 
Abbreviations: AUCinf = area under the curve at infinity; AUClast = area under the curve at the last time point; 
Cmax = maximum concentration; h = hour(s); mg = milligram(s); ND = not determinable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SEM = standard error of the mean; T1/2 = elimination half-life; tmax = time to maximum 
concentration.  
a Study Part 1b: Cohort 3 from Part 1a returned to receive a single oral dose of CBP-307 at 0.5 mg under fed conditions. 
Source: Final report for Study CBP-307AU001. 
For the repeated-dose administration of CBP-307, the Cmax and AUCs increased with the 
higher administered dose (Table 2). At the steady-state timepoint on Day 28, the median 
CBP-307 tmax was 4 to 6 hours. The average t1/2 was similar, ranging 44 to 49 hours, and 
there were no dose-dependent changes in t1/2 within the dose range. The t1/2 was slightly 
prolonged after repeated-dose administration when compared with that after a single-dose 
administration. Moderate accumulation of CBP-307 (approximately 3 times the levels 


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following a single dose) was noted in plasma after QD administration for 14 consecutive 
days. 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Multiple-Dose 
Regimen PK 
Parameters 
Multiple-Dose Cohort 1  
CBP-307 Dosing, mg (± SD) (n) 
Multiple-Dose Cohort 2  
CBP-307 Dosing, mg (± SD) (n) 
Day 1 
0.1 
Day 28 
0.25 
Day 1 
0.15 
Day 28 
0.15 
AUC0-24 
(ng*h/mL) 
24.5 ± 3.26 
(n = 5) 
125 ± 12.4 
(n = 4) 
26.3 ± 7.45 
(n = 5) 
79.7 ± 27.3 
(n = 6) 
AUClast 
(ng*h/mL) 
NA 
203 ± 21.9 
(n = 4) 
NA 
131 ± 44.7 
(n = 6) 
Cmax 
(ng/mL) 
1.45 ± 0.214 
(n = 5) 
6.30 ± 0.588 
(n = 4) 
1.32 ± 0.422 
(n = 6) 
4.23 ± 1.45 
(n = 6) 
tmax 
(hours) 
6.80 ± 1.50 
(n = 5) 
6.50 ± 1.50 
(n = 4) 
5.00 ± 0.68 
(n = 6) 
4.33 ± 0.33 
(n = 6) 
Abbreviations:  AUC0-24 = area under the curve from time 0 to 24 hours; AUClast = area under the curve at the last time 
point; Cmax = maximum concentration; mg = milligram(s); NA = not applicable; ng/mL = nanogram(s) per milliliter; PK = 
pharmacokinetic; SD = standard deviation; tmax = time to maximum concentration. 
Source: Final report for Study CBP-307AU001.
1.3. 
Overview of Moxifloxacin 
Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic that binds to and inhibits the 
hERG IKr α subunit and causes a mean increase of the QTc interval of 6 ms after a single 
400-mg oral dose. Moxifloxacin is commonly used as a positive control in thorough QT
(TQT) studies to satisfy the requirements of International Council for/Conference on
Harmonisation (ICH) E14.
Refer to the regional manufacturer package insert of AVELOX (moxifloxacin hydrochloride) 
tablets for additional information.2 
1.4. 
Study Rationale 
Regulatory guidance (ICH E14) has emphasized the need to obtain clear robust data on the 
effect of new chemical entities on electrocardiogram (ECG) parameters with focus on cardiac 
repolarization as measured by the QTc duration. Though many Phase 1, 2, and 3 trials may be 
conducted they usually have an insufficient sample size, infrequent sampling of ECG data, or 
the use of inadequate controls to overcome the high rate of spontaneous change in QTc 
duration. This has resulted in regulatory guidance recommending a dedicated or thorough 
trial to define the ECG effects of new drugs. 
This study will be done in healthy subjects to eliminate variables (concomitant drugs, 
diseases, etc.) known to have an effect on ECG parameters. A supratherapeutic dose of 
CBP-307 is required to mimic the exposure in healthy subjects that may occur in the target 
population under the worst of circumstances (eg, concomitant use of cytochrome P450 


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[CYP]3A4 inhibitor, concomitant liver disease, presence of heart disease, taking more than 
the clinical dose prescribed) and to allow for PK to QTc modeling to assess the effect of drug 
concentration on cardiac repolarization. 
1.5. 
Benefit-risk Assessment 
Healthy subjects in the current study will not receive any health benefit (beyond that of an 
assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from the collection of blood samples and other study 
procedures. More information about the known and expected benefits, risks, and reasonably 
anticipated AEs associated with CBP-307 may be found in the IB.1  
2. OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the PK of CBP-307 following administration of therapeutic and 
supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on HR, PR and QRS intervals, and T-wave morphology. 
2.2. 
Endpoints 
2.2.1. 
Electrocardiogram Endpoints 
2.2.1.1. 
Primary 
The primary endpoint is the change-from-baseline QTcF (ΔQTcF). 
2.2.1.2. 
Secondary  
The secondary endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 


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• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
2.2.2. 
Pharmacokinetic Endpoints 
Pharmacokinetic parameters of CBP-307 will be determined if data allows: 
• area under the concentration‑time curve from time zero extrapolated to infinity 
(AUCinf) 
• area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24) 
• maximum observed concentration (Cmax) 
• time of the maximum observed concentration (tmax) 
Other PK parameters may also be reported. 
2.2.3. 
Safety Endpoints 
The safety outcome measures for this study are as follows: 
• incidence and severity of AEs 
• incidence of laboratory abnormalities, based on hematology, clinical chemistry, and 
urinalysis test results 
• 12-lead ECG parameters 
• vital signs measurements. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only SAEs will be 
reported. After placebo administration to all subjects on Day -1, all AEs, whether 


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volunteered, elicited, or noted upon physical examination, will be recorded throughout the 
study (ie, from Day -1 until the end of the study).  
In this study, approximately 68 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 
Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec.  
An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
*Subjects will be asked to arrive at the clinical site in the afternoon 2 to 4 days before start of dosing on Day 1 
(on Day -4 or Day -2 depending on the clinical site’s requirements for Coronavirus Disease 2019 testing). 
Approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) 
with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be 
randomized with 17 subjects. Subjects will be randomized to receive a treatment sequence that includes 4 
treatments (CBP-307 therapeutic dose, CBP-307 supratherapeutic dose, moxifloxacin, or placebo [matched to 
CBP-307 or moxifloxacin]); assigned study treatments will be administered on Day 1, Day 2, Days 3 to 6, 
Days 7 to 15, and Day 16. Dosing details are provided in Table 3. Blood samples for pharmacokinetic analysis 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1
Day 2
*
*


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will be collected predose and at each postdose cardiodynamic electrocardiogram timepoint. Additional PK 
samples will be collected at 72 and 96 hours following dosing on Day 15. An end-of-study visit will occur on 
Day 29±2 days. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
(or on Day -4 depending on the clinical site’s requirement for Coronavirus Disease 2019 
[COVID-19] testing) and will remain at the study site until discharge on Day 19. Treatment 
administration will occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all 
subjects will receive placebo on Day -1). Continuous cardiodynamic ECG monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 6, 15, 
and 16 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15. Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 


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The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 
3.2. 
Discussion of Study Design 
The purpose of this study is to evaluate the potential for CBP-307 to cause QT prolongation. 
As CBP-307 exposure affects heart rate, the primary endpoint for this study will be the QTcF. 
The study will be randomized and double-blind because randomization eliminates 
confounding by baseline variables and blinding eliminates confounding by co-interventions, 
thus eliminating the possibility that the observed effects of the intervention are because of 
differential use of other treatments.  
The sample size for this study is based on a formal statistical power calculation. 
Conducting the study in healthy subjects mitigates the potential confounding effects of the 
disease state and concomitant medications. Both male and female subjects will be included to 
eliminate similar known ECG variability effects. 
Additionally, because food has been shown to alter the PK of CBP-307, subjects will be 
fasted at least 10 hours prior to dose administration and remain fasted for 4 hours postdose on 
the days when PK samples are collected. 
Pharmacokinetic assessments of CBP-307 concentrations in plasma will be evaluated during 
the study. The timepoints for the PK sample collections are based on previous studies and are 
considered adequate to allow for the characterization of the drug’s PK after oral dosing. 
Furthermore, the chosen PK sample collection for CBP-307 is anticipated to be sufficient to 
allow reasonable estimation of t1/2 during the terminal elimination phase.  
3.3. 
Selection of Doses in the Study 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To 
carefully monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 
doses will be up-titrated as follows: subjects will receive a starting dose of 0.05 mg CBP-307 
on Day 1 followed by an up-titrated dose of 0.1 mg on Day 2 and a dose of 0.2 mg on 
Days 3 to 6. Prior clinical experience with CBP-307 has not demonstrated clinically 
significant abnormalities in laboratory test results in the majority of subjects or a dose-
response relationship for safety based on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the 
characteristics of the study design with the safety of healthy subjects. Testing of CBP-307 at 


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substantial multiples of the anticipated maximum therapeutic exposure is not clinically 
warranted due to the known safety and tolerability profile of CBP-307.  
Further details are provided in the IB.1 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the screening visit unless otherwise 
stated: 
1. Males or females, of any race, between 18 and 60 years of age, inclusive. 
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive. 
3. In good health, determined by no clinically significant findings from medical history, 
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) at screening and 
confirmed at check-in as assessed by the investigator (or designee). 
4. Females will not be pregnant or lactating, and females of childbearing potential and 
males will agree to use contraception as detailed in Appendix 4. Negative pregnancy 
test for females of childbearing potential at screening (blood test) and check-in (urine 
test). 
5. Supine diastolic blood pressure between 60 and 90 mmHg and systolic blood pressure 
between 90 and 140 mmHg (inclusive) at screening on a single measurement 
(confirmed by a single repeat, if necessary) following at least 5 minutes of rest. 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
a. Normal sinus rhythm (HR between 55 bpm and 100 bpm inclusive); 
b. QTcF interval ≤450 msec for males and females; 
c. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
d. PR interval ≤200 msec. 
7. Has serum potassium, calcium, and magnesium levels within the normal reference 
range at screening, as judged by the investigator. 
8. Able to swallow multiple tablets (based on subject’s verbal confirmation). 
9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 


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4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
screening visit unless otherwise stated: 
1. Subject is mentally or legally incapacitated or has had significant history of recent 
mental health issues requiring medication and/or hospitalization at the time of the 
screening visit or expected during the conduct of the study. 
2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, 
hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the 
investigator (or designee). Note: Childhood asthma that is considered recovered or 
seasonal allergies that are not currently active or requiring treatment are allowed. 
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, unless approved by the investigator (or designee). 
4. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, 
related compounds, or inactive ingredients. 
5. History of significant multiple and/or severe allergies (eg, latex allergy, band-aids, 
adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant 
intolerability to prescription or nonprescription drugs. 
6. History of stomach or intestinal surgery or resection that would potentially alter 
absorption and/or excretion of orally administered drugs within 6 months prior to the 
first dose of study drug (uncomplicated appendectomy and hernia repair will be 
allowed). 
7. History or presence of: 
a. Hypokalemia, in the opinion of the investigator (or designee); 
b. Risk factors for Torsades de Pointes (eg, heart failure, cardiomyopathy, or 
family history of Long QT Syndrome); 
c. Sick sinus syndrome, second, or third degree atrioventricular block, 
myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged 
QT interval, or conduction abnormalities; 
d. Repeated or frequent syncope or vasovagal episodes; 
e. Hypertension, angina, bradycardia, or severe peripheral arterial circulatory 
disorders. 
8. Clinically significant abnormalities (as judged by the investigator in laboratory tests 
results [out-of-range results confirmed on repeat]), including but not limited to the 
following parameters: 
a. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or 
total bilirubin greater than 1.5 × upper limit of normal; 
b. hemoglobin <10 g/dL, WBC <3.0 ×109/L, neutrophils <1.5 ×109/L, 
lymphocytes <0.8 ×109/L and platelets <100 ×109/L or >1200 × 109/L; 


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9. History or evidence of alcoholism or drug/chemical abuse within 12 months prior to 
check-in. 
10. Alcohol consumption of >10 units per week for males and females. One unit of 
alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill 
(25 mL) of spirits. 
11. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) 
at screening or check-in.  
12. Positive hepatitis panel, positive syphilis test, and/or positive human 
immunodeficiency virus test (Appendix 2).  
13. Participation in a clinical study involving administration of an investigational drug 
(new chemical entity) in the past 28 days prior to the first dose of study treatment on 
Day 1. The 28-day window will be derived from the date of the last blood collection 
or dosing, whichever is later, in the previous study to Day 1 of the current study. 
14. Participation in a previous clinical study where subjects received CBP-307. 
15. Administration of a COVID-19 vaccine in the past 28 days prior to first dose of study 
treatment on Day 1. 
16. Use or intend to use any prescription medications/products within 14 days prior to 
first dose of study drug (Day 1) and throughout the study, unless deemed acceptable 
by the investigator (or designee). Note: For females only, the use hormonal 
contraception, hormone replacement therapy or oral, implantable, transdermal, 
injectable, or intrauterine hormonal contraceptives within 14 days prior to Day 1 is 
not acceptable, except for Mirena®. 
17. Use or intend to use any drugs known to be significant inhibitors or inducers of CYP 
enzymes and/or P-gp, including St. John’s Wort, for days prior to the first dose of 
study drug and throughout the study. Appropriate sources will be consulted by the 
investigator or designee to confirm the lack of PK/PD interaction with the study drug. 
18. Use or intend to use slow-release medications/products considered to still be active 
within 14 days prior to check-in, unless deemed acceptable by the investigator (or 
designee). 
19. Use or intend to use any nonprescription medications/products including antacids, 
vitamins (especially those containing magnesium, aluminum, iron, or zinc), minerals, 
and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to 
check-in, unless deemed acceptable by the investigator (or designee). 
20. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or 
positive cotinine at screening or check-in.  
21. Has been on a diet incompatible with the on-study diet (including an extreme diet 
which resulted in a significant weight change for whatever reason), in the opinion of 
the investigator, within the 28 days prior to the first dose of study treatment, and 
throughout the study. 
22. Consumption of caffeine/xanthine-containing foods or beverages within 48 hours 
prior to check-in until discharge. 


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23. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages 
within 7 days prior to check-in. 
24. Receipt of blood products within 2 months prior to check-in. 
25. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to 
screening, or platelets from 6 weeks prior to screening. 
26. Poor peripheral venous access. 
27. Subjects who, in the opinion of the investigator (or designee), should not participate 
in this study. 
4.3. 
Subject Number and Identification 
Subjects will have a unique identification number used at screening. Eligible subjects will be 
assigned a subject number prior to the first dosing occasion. Assignment of subject numbers 
will be in ascending order and no numbers will be omitted (eg, Subjects 0101, 0102, 0103). 
The screening number will be used on all safety samples throughout the study. Replacement 
subjects (Section 4.4) will be assigned a subject number corresponding to the number of the 
subject he/she is replacing plus 1000 (eg, Subject 1101 replaces Subject 0101). 
Subjects will be identified by screening identification number or subject number only on all 
study documentation. A list identifying the subjects by subject number will be kept in the site 
master file. 
4.4. 
Subject Withdrawal and Replacement 
A subject is free to withdraw their informed consent from the study at any time or they may 
be withdrawn at any time at the discretion of the investigator or the sponsor for safety, 
behavioral, or the inability of the subject to comply with the protocol-required visits or 
procedures. In addition, a subject will be withdrawn from dosing if any of the following 
criteria are met: 
• change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the investigator (or designee) 
• noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the investigator (or designee) 
• any clinically relevant sign or symptom that, in the opinion of the investigator (or 
designee), warrants subject withdrawal. 
If a subject is withdrawn from dosing, the sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic case report form (eCRF). If 
a subject is withdrawn from the study, efforts will be made to perform all follow-up 
assessments, if possible (Appendix 6). Other procedures may be performed at the 
investigator’s (or designee’s) and/or sponsor’s discretion. If the subject is in-house, these 
procedures should be performed before the subject is discharged from the clinic. The 
investigator (or designee) may also request that the subject return for an additional follow-up 
visit. All withdrawn subjects will be followed until resolution of all their AEs or until the 
unresolved AEs are judged by the investigator (or designee) to have stabilized. 


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If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, effort should be made to document subject outcome, if possible. 
The investigator should inquire about the reason for withdrawal, request the subject to return 
for a final visit, if applicable, and follow-up with the subject regarding any unresolved AEs.  
Subjects who are withdrawn for reasons not related to study treatment may be replaced 
following discussion between the investigator and the sponsor. Subjects withdrawn as a result 
of AEs thought to be related to the study treatment will generally not be replaced. 
4.5. 
Study Termination 
The study may be discontinued at the discretion of the investigator (or designee), sponsor, or 
sponsor’s medical monitor if any of the following criteria are met: 
• investigator decides to terminate the study due to safety concerns such as AEs 
unknown to date (ie, not previously reported in any similar investigational study drug 
trial with respect to their nature, severity, and/or duration) 
• increased frequency, severity, and/or duration of known, anticipated, or previously 
reported AEs (this may also apply to AEs defined at check-in as baseline signs and 
symptoms) 
• medical or ethical reasons affecting the continued performance of the study 
• difficulties in the recruitment of subjects 
• cancelation of drug development 
• sponsor requests for termination (eg, due to financial or management reasons, etc.) 
under the premise to fully protect the safety and rights of subjects  
• health authority or institutional review board (IRB)/ethics committee (EC) orders the 
termination of the trial for any reason. 
Definition of end-of-treatment and end-of-study  
• end-of-treatment is completion of safety follow-up or withdrawal from the study. 
End-of-study is the last visit by the last subject. 
5. STUDY TREATMENTS 
Study treatments are defined as any investigational product (IP), non-investigational product 
(non-IP), placebo, or medical device intended to be administered to a study subject according 
to the study protocol. 
Note that in several countries, IP and non-IP are referred to as IMP and non-IMP, 
respectively. 
5.1. 
Investigational Products 
The details regarding the storage, preparation, destruction, and administration of each 
treatment shown in Table 3 will be provided in a separate document. Approximately 


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68 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 
and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and 
each sub-group will be randomized with 17 subjects.  
Table 3: Study Treatments 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
1 capsule 
 
1 tablet 
Group 2A 
 
1 capsule 
 
1 tablet 
Group 2B 
 
1 capsule 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
electronic 
case report 
form (eCRF). 
subject's 
eCRF. 
subject's 
eCRF. 
subject's 
eCRF. 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
 
All supplies of the IMP, both bulk and subject-specific, will be stored in accordance with the 
manufacturer’s or pharmacy’s instructions. Until dispensed to the subjects, the study 
treatments will be stored at the study site in a location that is locked with restricted access. 
5.2. 
Study Treatment Administration 
Each dose of study treatment (CBP-307, placebo, or moxifloxacin) will be administered 
orally following an overnight fast of at least 10 hours, with approximately 240 mL of room 
temperature water. Additionally, because food has been shown to alter the PK of CBP-307, 
subjects will be fasted at least 10 hours prior to dose administration and remain fasted for 
4 hours postdose on the days when PK samples are collected. 
Subjects will be dosed in numerical order while sitting or standing but not be permitted to lie 
supine for 2 hours after treatment administration, except as necessitated by the occurrence of 
an AE(s) and/or study procedures. 
5.3. 
Randomization 
This is a double-blind randomized study. Subjects will be randomized to one of the treatment 
sequences before administration of the first dose of study treatment. A randomization list will 
be generated by a statistician using a computer-generated pseudo-random permutation 
procedure. The randomization date is to be documented in the subject’s medical record and 
on the enrollment eCRF. A computer-generated randomization schedule and emergency 
code-break envelopes will be provided to the study site. Randomization details will be 
included in the randomization specification. 


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5.4. 
Blinding 
This is a double-blinded study. The following controls will be employed to maintain the 
double-blind status of the study: 
• The placebo will be identical in appearance to CBP-307 or moxifloxacin. 
• The investigator and other members of staff involved with the study will remain 
blinded to the treatment randomization code during the assembly procedure. 
• Interim bioanalytical data will be provided to Labcorp Early Clinical Biometrics in a 
blinded manner. 
To maintain the blind, the investigator will be provided with a sealed randomization code for 
each subject, containing coded details of the treatment. These individually sealed envelopes 
will be kept in a limited access area that is accessible 24 hours a day. If, in order to manage 
subject safety or to support dose escalation decisions (in the event of possibly 
treatment-related SAEs or severe AEs), the decision to unblind resides solely with the 
investigator. Whenever possible, and providing it does not interfere with or delay any 
decision in the best interest of the subject, the investigator will discuss the intended 
code-break with the sponsor. If it becomes necessary to break the code during the study, the 
date, time, and reason will be recorded in the subject's source data and on the individual 
envelope and will be witnessed by a second person. 
5.5. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of suitably qualified study site 
staff. 
• Immediately after dose administration, visual inspection of the mouth and hands will 
be performed for each subject. 
• At each dosing occasion, a predose and postdose inventory of IMP will be performed.   
5.6. 
Drug Accountability 
The investigator (or designee) will maintain an accurate record of the receipt of study 
treatments (CBP-307, moxifloxacin, placebo-matched CBP-307, and placebo-matched 
moxifloxacin) received. In addition, an accurate drug disposition record will be kept, 
specifying the amount dispensed to each subject and the date of dispensing. This drug 
accountability record will be available for inspection at any time. At the completion of the 
study, the original drug accountability record will be available for review by the sponsor 
upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused 
assembled unit doses will be retained until the completion of the study. 


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At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the 
study site’s pharmacy, per the sponsor’s written instructions. If destruction is authorized to 
take place at the study site’s pharmacy, the investigator must ensure that the materials are 
destroyed in compliance with applicable environmental regulations and institutional policy. 
All study drug destructions must be adequately documented. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects will refrain from the use of any prescription or nonprescription medications/products 
during the study until the follow-up visit, unless the investigator (or designee) and/or sponsor 
have given their prior consent. Medications taken within 28 days before study treatment 
administration will be documented as a prior treatment. Treatments taken after study 
treatment administration will be documented as concomitant treatments. 
Paracetamol/acetaminophen (2 g/day for up to 3 consecutive days) is an acceptable 
concomitant medication. The administration of any other concomitant medications during the 
study is prohibited without prior approval of the investigator (or designee), unless its use is 
deemed necessary for the treatment of an AE. Any medication taken by a subject during the 
course of the study and the reason for its use will be documented in the source data.  
Females will refrain from the use of hormone replacement therapy and oral, implantable, 
transdermal, injectable, or intrauterine hormonal contraceptives (with the exception of 
Mirena®) during the study until the follow-up visit (Appendix 4). 
6.2. 
Diet 
While confined at the study site, subjects will receive a standardized diet at scheduled times 
that do not conflict with other study-related activities. Subjects will be fasted overnight (at 
least 10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be 
allowed from 7 days prior to check-in until follow-up visit on Day 29±2 days. 
Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 19. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge 
on Day 19 and alcohol intake will be limited to a maximum of 2 units/day on all other days, 
whilst not at the study site, from screening to 72 hours prior to the follow-up visit on 
Day 29±2 days.  


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6.3. 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 
3 months prior to check-in until the follow-up visit. 
6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 29±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 3 months prior to screening, 
plasma from 2 weeks prior to screening, and platelets from 6 weeks prior to screening until 
3 months after the follow-up visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. The order of 
priority for scheduling procedures around a timepoint is (in descending order of priority): 
• dosing 
• continuous ECG extraction window 
• pharmacokinetic blood samples 
• safety assessments  
• any other procedures. 
This study includes a screening period (Day -28 to Day -3 [or Day -5 depending on the 
clinical site’s requirement for COVID-19 testing]), a treatment period (Days -2 [or Day -4] to 
19), and a follow-up period (Day 29 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2 or 
Day -4 depending on the clinical site’s requirement for COVID-19 testing) or baseline 
(Day -1 predose) will only be considered exclusionary if judged applicable by the 
investigator. For confirmation of enrollment eligibility based on pulse rate, the pulse rate 
assessed by vital signs, rather than the 12-lead ECG, will be used. For all subjects, the 
screening, check-in, or baseline blood pressure, pulse rate, and respiratory rate may be 
repeated after 5 to 10 minutes if the initial reading is believed to be atypical for the subject. 


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7.1. 
General Assessments 
7.1.1. 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in order 
to study their possible association with subject safety and treatment effectiveness. 
7.1.2. 
Medical History 
At the timepoint specified in Appendix 6, the investigator or designee will collect a complete 
medical and surgical history. Medical history will include information on the subject’s 
concurrent medical conditions and any events occurring prior to the first dose of study 
treatment. All findings will be recorded on the medical history eCRF. 
7.2. 
Electrocardiography Assessments 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording 
Continuous 12-lead digital ECG recording will be performed as specified in Appendix 6. All 
ECG data will be collected using a Holter (or Mortara Surveyor) ECG continuous 12-lead 
digital recorder. The 12-lead Holter (or Mortara Surveyor) ECG equipment will be supplied 
and supported by ERT (eResearch Technology Inc., Philadelphia, PA). The continuous 
12-lead digital ECG data will be stored onto SD memory cards.  
The ECGs to be used in the analyses will be selected by predetermined timepoints as defined 
in Appendix 6 and will be read centrally by ERT (eResearch Technology Inc., Philadelphia, 
PA). The following principles will be followed in ERT’s core laboratory: 
• ECG analysts are blinded to the subject, visit, and treatment allocation. 
• Baseline and on-treatment ECGs for a particular subject will be over-read on the same 
lead and will be analyzed by the same reader. 
The primary analysis lead is lead II. If lead II is not analyzable, then the primary lead of 
analysis will be changed to another lead for the entire subject data set. 
The 12-lead ECGs will be extracted in up to 10 replicates at the predefined timepoints and 
subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 minutes 
after each nominal time. 
7.2.1.1. 
TQT Plus Extraction Technique 
Ten 14-second digital 12-lead ECG tracings will be extracted from the continuous Holter (or 
Mortara Surveyor) recordings using the ‘TQT Plus method’, a computer-assisted and 
statistical process utilized by ERT. The method enables extraction of ECGs with the lowest 
HR variability and noise within the protocol-specified extraction time window (eg, the HR 
and QT changes from beat-to-beat in the range of <10%). At each protocol-specified 
timepoint, 10 ECG replicates will be extracted from a 5-minute “ECG window” (typically, 


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the last 5 minutes of the 15-minute period when the subject is maintained in a supine, quiet 
position). 
7.2.1.2. 
Expert Precision QT Analysis 
Expert precision QT analysis will be performed on all analyzable (non-artifact) beats in the 
10 ECG replicates. Statistical quality control procedures are used to review and assess all 
beats and identify “high” and “low” confidence beats using several criteria, including: 
• QT or QTc values exceeding or below certain thresholds (biologically unlikely). 
• RR values exceeding or below certain thresholds (biologically unlikely). 
• Rapid changes in QT, QTc, or RR from beat-to-beat. 
Measurements of all primary ECG parameters (QT, QTc, RR) in all recorded beats of all 
replicates that are deemed “high confidence” will be performed using COMPAS software. 
All low-confidence beats will be reviewed manually and adjudicated using pass-fail criteria. 
The final QC assessment will be performed by a cardiologist. The beats found acceptable by 
manual review will be included in the analysis. The median QT, QTc, and RR values from 
each extracted replicate will be calculated, and then the mean of all available medians from a 
nominal timepoint will be used as the subject’s reportable value at that timepoint. 
Categorical T-wave morphology analysis and the measurement of PR and QRS interval of the 
ECG (QRS) intervals will be performed manually in 3 of the 10 ECG replicates at each 
timepoint. Each fiducial point (onset of P-wave, onset of Q-wave, offset of S-wave, and 
offset of T-wave) will be electronically marked. 
For T-wave morphology and U-wave presence, treatment-emergent changes will be assessed 
(ie, changes not present at baseline). For each category of T-wave morphology and U-waves, 
the category will be deemed as present if observed in any replicate at the timepoint. For 
baseline, the category will be deemed as present if observed in any replicate from all 
timepoints that constitute baseline. 
7.2.2. 
Safety 12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at 
least 5 minutes at the times indicated in the Schedule of Assessments in Appendix 6. Single 
12-lead ECGs will be repeated twice, and an average taken of the 3 readings, if either of the 
following criteria applies: 
• QT interval corrected for HR using Fridericia’s method (QTcF) is >500 ms 
• QTcF change from the baseline (predose) is >60 ms. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically 
appropriate or if the ongoing review of the data suggests a more detailed assessment of ECGs 
is required. The investigator (or designee) will perform a clinical assessment of each 12-lead 
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7.2.3. 
Cardiac Telemetry Monitoring 
Subjects will be monitored via cardiac telemetry from approximately 1 hour prior to dose 
administration and until approximately 12 hours postdose on Days 1, 2, 3, and 7 (up-titration 
days; as described in Appendix 6). Based on the emerging safety data from the study, the 
duration of the telemetry may be extended if necessary. 
The start and stop date and time of the telemetry monitoring will be recorded in the eCRFs. 
Clinically significant abnormalities noted from telemetry monitoring will be confirmed by 
12-lead ECG if necessary, then after confirming, the abnormities will be reported as AEs in 
the eCRF. 
7.3. 
Pharmacokinetic Assessments  
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples (approximately 1 × 4 mL for CBP-307 and moxifloxacin assays) will be 
collected by venipuncture or cannulation at the times indicated in the Schedule of 
Assessments in Appendix 6. Procedures for collection, processing, and shipping of PK blood 
samples will be detailed in a separate document.  
7.3.2. 
Analytical Methodology 
Plasma concentrations of CBP-307 and moxifloxacin will be determined using a validated 
analytical procedure. Specifics of the analytical method will be provided in a separate 
document.  
7.4. 
Safety and Tolerability Assessments 
7.4.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF until the 
follow-up visit. Subjects will be observed for any signs or symptoms and asked about their 
condition by open questioning, such as “How have you been feeling since you were last 
asked?”, at least once each day while resident at the study site and each study visit. Subjects 
will also be encouraged to spontaneously report AEs occurring at any other time during the 
study. 
All nonserious AEs, whether reported by the subject voluntarily or upon questioning, or 
noted on physical examination, will be recorded from initiation of placebo administration to 
all subjects (Day -1) until study completion. If AEs that occur in the screening prior to 
placebo administration to all subjects (Day -1) are considered to be related to the study 
procedure, they should be also collected. Serious AEs will be recorded from the time the 
subject signs the ICF until study completion. The nature, time of onset, duration, and severity 
will be documented, together with an investigator’s (or designee’s) opinion of the 
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Adverse events recorded during the course of the study will be followed up, where possible, 
to resolution or until the unresolved AEs are judged by the investigator (or designee) to have 
stabilized. This will be completed at the investigator’s (or designee’s) discretion. 
7.4.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations at the times 
indicated in the Schedule of Assessments in Appendix 6. Clinical laboratory evaluations are 
listed in Appendix 2. 
A serum qualitative pregnancy or urine test (females only) and follicle-stimulating hormone 
test (postmenopausal females only) will be performed at the timepoints specified in 
Appendix 6. A positive urine pregnancy test will be confirmed with a serum pregnancy test. 
All pregnancies should be reported as specified in Appendix 1. 
Additional clinical laboratory evaluations will be performed at other times if judged to be 
clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of clinical laboratory safety evaluations is required. At the discretion of the 
investigator, clinically significant clinical laboratory assessments may be confirmed by repeat 
sampling. If the clinical significance is confirmed, subjects will be excluded from 
participation or, if already included, will be followed until normalization of the test result or 
for as long as the investigator considers necessary. 
Subjects will be asked to provide urine samples for drugs of abuse screen and cotinine test, 
and will undergo an alcohol breath test at the times indicated in the Schedule of Assessments 
in Appendix 6. For all female subjects, a pregnancy test will be performed at the times 
indicated in the Schedule of Assessments in Appendix 6.   
An investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.4.3. 
Vital Signs 
Supine blood pressure, supine pulse rate, respiratory rate, and tympanic temperature will be 
assessed at the times indicated in the Schedule of Assessments in Appendix 6. Vital signs 
may also be performed at other times if judged to be clinically appropriate or if the ongoing 
review of the data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly. For all subjects, the screening, check-in, or 
baseline blood pressure, pulse rate, and respiratory rate may be repeated after 5 to 10 minutes 
if the initial reading is believed to be atypical for the subject. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
7.4.4. 
Physical Examination 
A full physical examination will be performed at the timepoints specified in the Schedule of 
Assessments in Appendix 6. Physical examinations include general appearance, head, eyes, 


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ears, nose, and throat, neck (including thyroid and nodes), cardiovascular, respiratory, 
gastrointestinal, renal, neurological, musculoskeletal, skin, and others. 
Height, weight, and body mass index will be assessed at screening. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
Approximately 68 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Sample Size for Primary Analysis: 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-msec QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-307 
in the study. This power is estimated approximately using a 2-sample t-test. The calculation 
assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 3 msec and a 
standard deviation (SD) of the ΔQTcF of 8 msec for both CBP-307 and placebo treatment 
groups. Note that this calculation is conservative, since it does not take into account any gain 
in precision due to the use of all data of each subject with the help of a linear mixed-effects 
model. The concentration-QTc analysis method is supported by Darpo et al 20153 and 
Ferber et al, 2015,4 and consistent with the experiences from 25 recent TQT studies. 
Sample Size Considerations for Assay Sensitivity: 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that the 
ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 msec (ie, the lower bound of the 
2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 msec). In a similarly 
designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the standard 
error (SE) for the prediction of the QT effect of moxifloxacin based on the exposure-response 
analysis was 1.24 msec. The within-subject SD of ΔQTcF in the referred study was 5.4 msec 
based on the by-timepoint analysis. If the effect of moxifloxacin is assumed to be 10 msec, 
the SE of 1.24 msec corresponds to an effect size of (10-5)/(1.24×sqrt[24])=0.82, where the 
effect size is the effect assumed under the alternative hypothesis divided by the SD of the test 
variable. This value should be compared to the effect size of 0.64 required to guarantee a 
power of at least 95% in a paired t-test situation with a sample size of 28 evaluable subjects. 
In other words, based on this calculation, a power of at least 95% will be obtained as long as 
the variability of the ΔQTcF, as measured by its within-subject SD from the by-timepoint 
analysis, does not exceed 6.9 msec (ie, 128% [= 0.82/0.64] of the 5.4 msec observed in the 
referred study assuming the ratio of effective sizes is consistent with inverse ratio of 
within-subject SD). The number also agrees with recent recommendations of the FDA, which 
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8.2. 
Analysis Populations 
8.2.1. 
Cardiodynamic Population 
The QT/QTc population will include all subjects in the safety population with measurements 
at baseline as well as on-treatment with at least 1 postdose timepoint with a valid ΔQTcF 
value. The QT/QTc population will be used for the by-timepoint and categorical analyses of 
the cardiodynamic ECG parameters. 
The PK/QTc population will include all subjects who are in both the QT/QTc and PK 
populations with at least 1 pair of postdose PK and ∆QTcF data from the same timepoint as 
well as subjects in the QT/QTc population who received placebo. The PK/QTc population 
will be used for the concentration-QTc analysis and assay sensitivity. PK/QTc population 
will be defined for CBP-307, and for moxifloxacin.  
The as-treated principle will be applied to all analysis populations mentioned below. 
8.2.2. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of investigational 
product and have evaluable PK data of any of the analytes (CBP-307 and moxifloxacin). A 
subject will be excluded from the PK summary statistics and statistical analysis if the subject 
has an AE of vomiting that occurs at or before 2 times median time to maximum 
concentration.  
8.2.3. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of investigational 
product drug (therapeutic and supratherapeutic doses of CBP-307, moxifloxacin, or placebo). 
8.3. 
Cardiodynamic ECG Analyses 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus 
placebo in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1 (defined as Period 1 Day 1), 
baseline will be Day 16 (defined as Period 1 Day -1), on which subjects are 
administered placebo. For placebo-correction in this group, placebo values will be 
derived from Day 15 (defined as Period 2 Day 1) on which subjects are administered 
placebo, and baseline will be obtained on Day -1 (defined as Period 2 Day -1). 
• Group 2B: For moxifloxacin administered on Day 16 (defined as Period 2 Day 1), 
baseline will be Day 1 (defined as Period 2 Day -1), on which subjects are 
administered placebo. For the placebo-correction in this group, Day -1 (defined as 


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Period 1 Day 1) values will be used as placebo (no treatment) and baseline will be 
obtained on Day 15 (defined as Period 1 Day -1). 
Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as 
the dependent variable, time-matched concentrations of CBP-307 as the exploratory variate 
(0 for placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on 
Days 1, 6, and 15 categorical) as fixed effects, and a random intercept and slope per subject.6 
Centered baseline QTcF (i.e., baseline QTcF for individual subject minus the population 
mean baseline QTcF for all subjects) will be included in this model as an additional covariate. 
If necessary, a sensitivity analysis will be performed using the model without this term. 
The degrees of freedom estimates will be determined by the Kenward-Roger method. From 
the model, the slope (ie, the regression parameter for the CBP-307 concentration) and the 
treatment effect-specific intercept will be estimated together with 2-sided 90% CI. The 
estimates for the time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-timepoint analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 6, 
and 15, and Days 1 and 16 for active versus placebo and moxifloxacin versus placebo, 
respectively. All times are relative to the time of dosing on that day which is considered the 
first dose for the assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the 
first dose of study treatment is on Day 1. 
The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in 
the active drug groups on each of Days 6 and 15 will be determined, respectively. The 
predicted effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF 
(ΔΔQTcF) (ie, slope estimate × concentration + treatment effect-specific intercept) at this 
geometric mean Cmax will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the 
observed ΔQTcF values adjusted by population time effect estimated from the model will be 
used. These individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed 
individual ΔQTcFi,k for subject i administered with active drug or placebo at timepoint k 
minus the estimated population mean placebo effect at timepoint k (ie, time effect). A decile 
plot, ie, plot of the deciles of observed concentrations and the mean placebo-adjusted ΔQTcF 
(ΔΔQTcF) and 90% CI at the median concentration within each decile will be given. The 
regression line presenting the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a 
linear model and visualize the concentration-response relationship. The placebo-adjusted 
ΔQTcFi,j equals the individual ΔQTcFi,j for subject i administered with CBP-307 at timepoint 
j minus the estimation of time at timepoint j (ie, time effect). Additional exploratory analyses 
(via graphical displays and/or model fitting) will include accounting for a delayed effect 
(hysteresis) and the justification for the choice of PD model (linear versus nonlinear) as 
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Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the 
observed geometric mean Cmax on Days 6 and 15 as well as clinically relevant plasma levels 
is below 10 msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax 
<10 msec), it can be concluded that CBP-307 does not cause clinically concerning QT 
prolongation within the observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 6 and 15; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on 
Days 6 and 15; and if the difference (delay) between the time to reach the peak QTc effect 
(ΔΔQTcF) and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of 
more than 1 hour is observed in a consistent way for the active dose groups on Days 6 and 15, 
other concentration-QTc models, such as a model with an effect compartment, may be 
explored. With the provision stated above, hysteresis will be assumed if this curve shows a 
counterclockwise loop. A significant treatment effect-specific intercept may also be 
indicative of hysteresis or model misspecification, if it cannot be explained by a nonlinear 
relationship. 
Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 
time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a 
scatter plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI 
and a linear regression line will also be provided to check the assumption of a linear 
concentration-QTc relationship. If there is an indication that a linear model is inappropriate, 
additional models may be fitted, such as an E-max model. The concentration-QTc analysis 
will then be repeated for the model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of 
moxifloxacin data. If the slope of the concentration-QTc (change-from-baseline QTcF) for 
moxifloxacin is statistically significant at 10% level for 2-sided test and the lower bound of 
the 2-sided 90% CI of the predicted effect is above 5 msec at the observed geometric mean 
Cmax of the 400-mg dose, assay sensitivity will be deemed to have been demonstrated. 


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By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 
time-by-treatment interaction as fixed effects. Baseline QTcF will be included in this model 
as an additional covariate. If necessary, a sensitivity analysis will be performed using the 
model without this term. An unstructured covariance matrix will be specified for the repeated 
measures at postdose timepoints within subjects. If the model with unstructured covariance 
matrix fails to converge, other covariance matrices such as compound symmetry and 
autoregressive will be considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs 
will be calculated for the contrast “CBP-307 versus placebo” for each day of Days 1, 6, and 
15 at each postbaseline timepoint on Days 1, 6, and Day 15, respectively. 
The by-timepoint analysis for QTcF will be also performed for moxifloxacin versus placebo 
at postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used 
with ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 
16: categorical), treatment (moxifloxacin and placebo), period (as described in baseline 
definition for assay sensitivity), sequence (placebo/moxifloxacin or moxifloxacin/placebo), 
and time-by-treatment interaction as fixed effects. Baseline QTcF will be included in this 
model as an additional covariate. If necessary, a sensitivity analysis will be performed using 
the model without this term. An unstructured covariance matrix will be specified for the 
repeated measures at postbaseline timepoints for subject within visit. The model will also 
include a subject-specific random effect. If the model with an unstructured covariance matrix 
fails to converge, other covariance matrices, such as compound symmetry or autoregressive, 
will be considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs will be 
calculated for the contrast “moxifloxacin versus placebo” at each postbaseline timepoint on 
Day 1, respectively. 
For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline 
postdose (ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as 
described for QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both 
change-from-baseline and placebo-corrected change-from-baseline values will be listed in the 
tables and graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will 
be summarized in frequency tables with counts (percentages) for both the number of subjects 
and the number of timepoints. For categorical outliers, the number (percentage) of subjects as 
well as timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 
and ≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline 
>25% to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR 
>100 bpm will be determined. For T-wave morphology and U-wave presence, the analyses 
will be focused on change from baseline (ie, treatment-emergent changes). 


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8.4. 
Pharmacokinetic Analyses 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, SD, median, minimum, 
maximum geometric mean, and geometric coefficient of variation) separately by group. 
Individual and mean plasma CBP-307 and moxifloxacin concentration versus time data will 
be tabulated and plotted by dose level. Graphical displays of PK data may be provided as 
well.  
For each subject, the following PK parameters will be calculated, whenever possible, based 
on the plasma concentration for CBP-307 and moxifloxacin, according to the model 
independent approach: 
• Cmax 
• tmax 
• AUC0-24  
• AUCinf 
• apparent terminal elimination rate constant (λZ) 
• t1/2  
• apparent total clearance (CL/F) 
• apparent volume of distribution during the terminal phase (Vz/F)  
Pharmacokinetic calculations will be performed, if appropriate, using commercial software 
such as Phoenix® WinNonlin® (Version 8.1 or higher). 
Other parameters may be added as appropriate. 
Pharmacokinetic analysis will use actual times as recorded on the eCRF. Other data handling 
procedures will be detailed in the Statistical Analysis Plan. 
8.5. 
Safety Analysis 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed.   
8.6. 
Interim Analysis 
No interim analyses are planned for this study.  


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9. REFERENCES 
1. Suzhou Connect. CBP-307 – Investigator’s Brochure. (Version 6.0). December 2020. 
2. Avelox [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016. 
3. Darpo B, Benson C, Dota C, et al. Results from the IQ-CSRC prospective study support 
replacement of the thorough QT study by QT assessment in the early clinical phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
4. Ferber G, M Zhou, B Darpo. Detection of QTc effects in small studies--implications for 
replacing the thorough QT study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
5. Huang DP, Chen J, Dang Q, et al. Assay sensitivity in “Hybrid thorough QT/QTc (TQT)” 
study. Journal of Biopharmaceutical Statistics. 2019;29(2):378-384. 
6. Garnett C, Bonate PL, Dang Q , et al. Scientific white paper on concentration-QTc 
modeling. [Published correction appears in J Pharmacokinet Pharmacodyn. 
2018;45(3):399]. J Pharmacokinet Pharmacodyn. 2018;45(3):383-397. 
7. Tornøe CW, Garnett CE, Wang Y, et al. Creation of a knowledge management system for 
QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042. 
8. Cleveland WS. Robust Locally Weighted Regression and Smoothing Scatter Plots. 
J Amer Statist Assoc. 1979;74(368):829-36. 
9. Hurvich CM, Simonoff JS, Tsai CL. Smoothing parameter selection in nonparametric 
regression using an improved Akaike information criterion. J Roy Statist Soc Ser B Stat 
Methodol. 1998;60(2):27-193. 
 
 


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10. APPENDICES 


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Appendix 1: Adverse Event Reporting 
Definitions 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a study treatment, whether or not related to the study 
treatment. This includes any newly occurring event or previous condition that had increased 
in severity or frequency since the administration of study medication.  
Examples of AEs include: 
• Symptoms described by the subject, or signs observed by the investigator, and 
• Abnormal findings (involving clinically significant abnormal laboratory tests, ECG, 
etc.)  
• Exacerbation of previous condition, including increased incidence and/or severity. 
Note: Regarding decreased lymphocyte count in peripheral blood in this study, please report 
them as follows: 
• Since a decreased lymphocyte count in peripheral blood is due to the mechanism of 
action of the drug, it is not to be reported as an AE. However, clinical diagnosis 
related to a decreased lymphocyte count in peripheral blood indicates AE reporting (if 
no diagnosis is available, it is required to report related clinical symptoms or signs). 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs. All AEs will 
be recorded in the medical records and eCRFs. The investigator (or designee) is to record in 
detail any AE that occurred to the subject, including: AE diagnosis whenever possible, or 
signs, symptoms, the start date and time of occurrence, the stop date and time of occurrence, 
seriousness (ie, whether it is an SAE), severity of AEs, causality assessment, actions taken on 
the investigational product, other actions (eg, medications/treatments given), and outcomes of 
AEs.  
Assessment of Severity 
The investigator will be asked to provide an assessment of the severity of the AE using the 
following categories:  
• Mild: Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily 
living. 
• Moderate: Usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 


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• Severe: Interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
Relationship to Study Treatment 
The investigator (or designee) will make a determination of the relationship of the AE to the 
study treatment using a 4-category system according to the following guidelines: 
• Not Related: The AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions. 
• Unlikely Related: The temporal association between the AE and the drug is such that 
the drug is not likely to have any reasonable association with the AE. 
• Possibly Related: The AE follows a reasonable temporal sequence from the time of 
drug administration but could have been produced by the subject’s clinical state or the 
study procedures/conditions. 
• Related: The AE follows a reasonable temporal sequence from the administration of 
the drug, abates upon discontinuation of the drug, follows a known or hypothesized 
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced.  
Follow-up of Adverse Events 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject 
who has an ongoing AE that is possibly related or related to the IMP or study procedures at 
the follow-up visit will be followed up, where possible, until resolution or until the 
unresolved AE is judged by the investigator (or designee) to have stabilized. This will be 
completed at the investigator’s (or designee’s) discretion. Any subject who has an ongoing 
AE that is not related or unlikely related to the IMP or study procedures at the follow-up visit 
can be closed out as ongoing at the investigator’s discretion.  
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
For marketed medicinal products, a response to a drug that is noxious and unintended and 
which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases 
or modification of physiological function is to be considered an adverse drug reaction. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, IB for an unapproved 
IMP). 
Serious Adverse Events 
All SAEs will be collected after subjects sign the informed consent form and throughout the 
entire study, ie, until the end-of-study as specified in the protocol (or at early termination). 


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An SAE is defined as any untoward medical occurrence that at any dose either: 
• results in death 
• is life-threatening 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
• results in a congenital anomaly/birth defect 
• results in an important medical event (see below). 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Instances of death or congenital abnormality, if brought to the attention of the investigator at 
any time after cessation of the study treatment and considered by the investigator to be 
possibly related to the study treatment, will be reported to the sponsor (or designee). 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalization 
Adverse events requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the subject has been detained (usually involving an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate at the study site. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered as serious. 
Hospitalization for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a clinical assessment form and 
added to the eCRF. If anything untoward is reported during the procedure, this must be 
reported as an AE and either ‘serious’ or ‘nonserious’ attributed according to the usual 
criteria. 
Serious Adverse Event Reporting 
The investigator will complete an SAE report form and forward it by facsimile or email to 
Labcorp Drug Safety and the sponsor immediately (within 24 hours) upon becoming aware of 
an SAE. 


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All SAEs must be reported immediately (within 24 hours of discovery) to:  
+61-2-8879-2000 (AUS) or 1-888-887-8097 (US) 
SAE Reporting email: SAEIntake@labcorp.com (preferred method) 
Labcorp Safety SAE Reporting Fax Numbers: 61-2-6100-9788 or 1800-882-203 (toll free) in 
Australia and 1-888-887-8097 (toll free) in the US 
The responsibilities of Labcorp Drug Safety include the following: 
• Prepare an AE reporting plan prior to the start of the study. Where this plan differs 
from the applicable study site standard operating procedure on SAE reporting, the 
safety management plan will always take precedence. 
• Receive and review SAE report forms from the study site and inform the sponsor of 
the SAE within 1 working day of the initial notification to Labcorp Drug Safety  who 
will delete any information from the SAE report forms that may identify the subject. 
• Write case narratives and enter the case into Labcorp’s safety database as defined in 
the AE reporting plan. 
• Produce appropriate reports of all suspected unexpected serious adverse reactions and 
forward them to the IRB/EC, Medicines and Healthcare Products Regulatory Agency, 
FDA, principal investigator, and the sponsor within the timeframes stipulated in the 
Clinical Trials Directive Guideline (ENTR/CT 3).  
The responsibility for reporting SAEs will be transferred to the sponsor 28 days after the end 
of the study. 
For SAEs, the active reporting period to sponsor or its designated representative begins from 
the time that the subject provides informed consent through to the last subject visit.  
Nonserious AEs should be collected from the time the subject has taken the placebo dose on 
Day -1 through the last subject visit. If AEs that occur in the screening prior to the placebo 
administration to all subjects on Day -1 are considered to be related to the study procedure, 
they should be also collected.  
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, the 
sponsor should be notified within 24 hours of investigator awareness of the event. This time 
frame also applies to additional new information (follow-up) on previously forwarded SAE 
reports as well as to the initial and follow-up reporting of exposure during pregnancy.  
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.  
For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the time frames for reporting as specified above. In addition, an investigator 


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may be requested by the sponsor to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured on 
the AE eCRF. In general, this will include a description of the AE in sufficient detail to allow 
for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to the sponsor 
or its designated representative. 
Pregnancy 
Pregnancy (maternal or paternal exposure to study treatment) does not meet the definition of 
an AE. However, to fulfill regulatory requirements any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus. 
If the female subject becomes pregnant during the clinical trial and has not yet been dosed 
with study treatment, she must be withdrawn from the study. If the female subject becomes 
pregnant during the clinical trial and has been dosed, she must discontinue treatment 
immediately but may remain on study for safety evaluations. If the partner of a male subject 
becomes pregnant during the clinical trial, the subject can continue the clinical trial.  
For pregnancy of female subjects or partners of the male subjects during this study, 
investigators should report to the sponsor or designee in a pregnancy report form within 
24 hours after investigator awareness and report to the IRB/EC in time as per local 
requirement.  
The investigator will follow up on pregnancy outcomes, until not less than 12 months after 
birth, unless otherwise justified, and will report the outcome to the sponsor and IRB/EC.  
If any adverse pregnancy outcome (eg, the outcome of the pregnancy is stillbirth, 
spontaneous abortion, or fetal malformations), it should be considered as an SAE and be 
reported in accordance with SAE reporting requirements. 
 
 


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Protocol Version 5.0, 12 January 2022  
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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate  
Magnesium 
Potassium  
Sodium  
Total bilirubin 
Total protein 
Urea 
Uric acid 
Hematocrit  
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell count 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
 
Blood 
Glucose 
Ketones 
Leukocyte esterase  
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination  (if 
indicated by dipstick) 
Serology: 
Drug screen: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency (HIV-1 
and HIV-2) antibodies and p24 
antigen 
Syphilis 
Including but not limited to:  
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol 
Tricyclic antidepressants 
Cotinine test 
Follicle-stimulating hormone 
(postmenopausal females only) 
Serum pregnancy test (human 
chorionic gonadotropin)b 
Urine pregnancy testb  
Other Tests 
Low density lipoprotein cholesterol 
High-density lipoprotein 
cholesterol 
Triglycerides 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated.  
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed at check-in (on Day -4 or 
Day -2 depending on the clinical site’s requirements for Coronavirus Disease 2019 testing) and at the follow-up visit (on 
Day 29±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  


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Protocol Version 5.0, 12 January 2022  
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Appendix 3: Total Blood Volume 
The following blood volumes will be withdrawn for each subject. 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
41 
328 
Total: 
390.5 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed 500 mL. 


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Protocol Version 5.0, 12 January 2022  
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Appendix 4: Contraception Guidance 
Definitions 
Women of Childbearing Potential: premenopausal females who are anatomically and 
physiologically capable of becoming pregnant following menarche. 
Women of Nonchildbearing Potential:  
1. Surgically sterile: females who are permanently sterile via hysterectomy, 
bilateral salpingectomy, and/or bilateral oophorectomy by reported medical 
history and/or medical records. Surgical sterilization to have occurred a minimum 
of 6 weeks, or at the investigator’s discretion, prior to screening. 
2. Postmenopausal: females at least 45 years of age with amenorrhea for 12 months 
without an alternative medical reason with confirmatory follicle-stimulating 
hormone (FSH) levels of ≥40 mIU/mL. The amenorrhea should not be induced by 
a medical condition such as anorexia nervosa, hypothyroid disease or polycystic 
ovarian disease, or by extreme exercise. It should not be due to concomitant 
medications that may have induced the amenorrhea such as oral contraceptives, 
hormones, gonadotropin-releasing hormones, anti-estrogens, or selective estrogen 
receptor modulators. Females on hormone replacement therapy with FSH levels 
<40 mIU/mL may be included at the discretion of the investigator.   
Fertile male: a male that is considered fertile after puberty. 
Infertile male: permanently sterile male via bilateral orchiectomy. 
Contraception Guidance 
Female Subjects 
Female subjects who are of nonchildbearing potential will not be required to use 
contraception. Female subjects of childbearing potential must be willing to use 2 methods 
(1 primary and 1 secondary method) of birth control from the time of signing the ICF until 
90 days after the follow-up visit. Primary (non-barrier) methods of contraception include: 
• surgical method performed at least 3 months prior to the screening visit: 
o 
bilateral tubal ligation or bilateral salpingectomy 
o 
Essure® (hysteroscopic bilateral tubal occlusion) with confirmation of 
occlusion of the fallopian tubes 
• non-hormonal intrauterine device or Mirena® (other hormonal intrauterine devices 
will not be allowed) in place for at least 3 months prior to the first dose of the study 
drug 
• vasectomized male partner (sterilization performed at least 90 days prior to the 
screening visit, with verbal confirmation of surgical success, and the sole partner for 
the female subject)  


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Protocol Version 5.0, 12 January 2022 
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Secondary (barrier) methods of contraception include: 
•
male condom without spermicide
•
female condom without spermicide
•
cervical cap without spermicide (as prescribed)
•
diaphragm without spermicide (as prescribed).
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2 or Day -4 depending on the clinical site’s requirement for COVID-19 testing) until 
90 days after the follow-up visit. 
Male Subjects 
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (ie, male condom without spermicide) in addition 
to a second method of acceptable contraception from check-in until 90 days after the 
follow-up visit. Acceptable methods of contraception for female partners include: 
•
hormonal injection
•
combined oral contraceptive pill or progestin/progestogen-only pill
•
combined hormonal patch
•
combined hormonal vaginal ring
•
surgical method (bilateral tubal ligation or Essure® [hysteroscopic bilateral tubal
occlusion])
•
hormonal implant
•
hormonal or non-hormonal intrauterine device
•
cervical cap without spermicide
•
diaphragm without spermicide.
An acceptable second method of contraception for male subjects is vasectomy that has been 
performed at least 90 days prior to the screening visit with verbal confirmation of surgical 
success. 
For male subjects (even with a history of vasectomy), sexual intercourse with female partners 
who are pregnant or breastfeeding should be avoided unless condoms are used from the time 
of the first dose until 90 days after the follow-up visit. Male subjects are required to refrain 
from donation of sperm from check-in until 90 days after the follow-up visit. 
Sexual Abstinence and Same-sex Relationships 
Subjects who practice true abstinence, because of the subject’s lifestyle choice (ie, the subject 
should not become abstinent just for the purpose of study participation), are exempt from 
contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, symptothermal, 


Protocol Amendment 4 
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Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 59 of 67 
postovulation methods) and withdrawal are not acceptable methods of contraception. If a 
subject who is abstinent at the time of signing the ICF becomes sexually active they must 
agree to use contraception as described previously.  
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. If a subject who is in a same-sex relationship at the time of signing the ICF becomes 
engaged in a heterosexual relationship, they must agree to use contraception as described 
previously. 


Protocol Amendment 4 
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Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 60 of 67 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol, local legal and regulatory 
requirements and with the following: 
•
General principles set forth in the International Ethical Guidelines for Biomedical
Research Involving Human Subjects (Council for International Organizations of
Medical Sciences 2002), Guidelines for good clinical practice (GCP) (ICH 1996), and
the Declaration of Helsinki (World Medical Association 2008).
•
Applicable laws and regulations.
The protocol, protocol amendments, ICF, IB, and other relevant documents must be 
submitted to the institutional review board (IRB)/human research ethics committee (HREC) 
by the investigator and reviewed and approved by the IRB/HREC before the study is 
initiated.  
Any protocol amendments will require IRB/EC approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study subjects.  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents from the 
IRB/HREC. All correspondence with HREC should be retained in the investigator file. A 
copy of /IRB/HREC approval should be forwarded to the sponsor. 
The investigator will be responsible for the following: 
•
Providing written summaries of the status of the study to the IRB/EC annually or
more frequently in accordance with the requirements, policies, and procedures
established by the IRB/EC.
•
Notifying the IRB/EC of SAEs or other significant safety findings as required by
IRB/EC procedures.
•
Providing oversight of the conduct of the study at the site and adherence to
requirements of ICH guidelines, the IRB/EC, and all other applicable local
regulations.
Regulatory Authority 
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency 
in accordance with any applicable country-specific regulatory requirements before the study 
is initiated at a study center in that country. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 61 of 67 
Informed Consent 
Prior to starting participation in the study, each subject will be provided with a study-specific 
ICF giving details of the study treatments, procedures, and potential risks of the study. 
Subjects will be instructed that they are free to obtain further information from the 
investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. Subjects will be given an opportunity to ask questions 
about the study prior to providing consent for participation. 
Following the discussion of the study with study site personnel, subjects will sign the ICF in 
the presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. A copy of the ICF will be given to the subject. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
Subject Data Protection 
Subjects will be assigned a unique identifier and will not be identified by name in eCRFs, 
study-related forms, study reports, or any related publications. Subject and investigator 
personal data will be treated in compliance with all applicable laws and regulations. In the 
event the study protocol, study report, or study data are included in a public registry, all 
identifiable information from individual subjects or investigators will be redacted according 
to applicable laws and regulations.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. The subject must also be informed that his/her study-related data 
may be examined by sponsor or contract research organization (CRO) auditors or other 
authorized personnel appointed by the sponsor, by appropriate IRB/EC members, and by 
inspectors from regulatory authorities. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the sponsor. 
Data Quality Assurance 
The following data quality steps will be implemented: 
•
All relevant subject data relating to the study will be recorded on eCRFs unless
directly transmitted to the sponsor or designee electronically (eg, laboratory data). The
investigator is responsible for verifying that data entries are accurate and correct by
electronically signing the eCRF.


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Protocol Version 5.0, 12 January 2022 
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•
The investigator must maintain accurate documentation (source data) that supports the
information entered in the eCRF.
•
The investigator must permit study-related monitoring, audits, IRB/EC review, and
regulatory agency inspections and provide direct access to source data documents.
•
The sponsor or designee is responsible for the data management of this study
including quality checking of the data. Predefined agreed risks, monitoring thresholds,
quality tolerance thresholds, controls, and mitigation plans will be documented in a
risk management register. Additional details of quality checking to be performed on
the data may be included in a data management plan.
•
A study monitor will perform ongoing source data verification to confirm that data
entered into the eCRF by authorized site personnel are accurate, complete, and
verifiable from source documents; that the safety and rights of subjects are being
protected; and that the study is being conducted in accordance with the currently
approved protocol and any other study agreements, ICH GCP, and all applicable
regulatory requirements.
•
Records and documents, including signed ICFs, pertaining to the conduct of this study
must be retained by the investigator in the study site archive in accordance with 21
CFR 312.62(c) or for at least 5 years after the end of the study unless local regulations
or institutional policies require a longer retention period. No records may be destroyed
during the retention period without the written approval of the sponsor. No records
may be transferred to another location or party without written notification to the
sponsor.
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 Code of Federal 
Regulations Part 11-compliant electronic data capture (EDC) system on an eCRF in a timely 
fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and 
transmitted to the sponsor or designee electronically, will be integrated with the subject’s 
eCRF data in accordance with the data management plan.  
An eCRF must be completed for each enrolled subject who undergoes any screening 
procedures, according to the eCRF completion instructions. The sponsor, or CRO, will 
review the supporting source documentation against the data entered into the eCRFs to verify 
the accuracy of the electronic data. The investigator will ensure that corrections are made to 
the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The investigator will sign and date the eCRF via the EDC system’s electronic signature 
procedure. These signatures will indicate that the investigator reviewed and approved the data 
on the eCRF, data queries, and site notifications. 


Protocol Amendment 4 
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Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 63 of 67 
Publications 
Publications will be addressed as follows:The results of this study may be published or 
presented at scientific meetings. If this is foreseen, the investigator agrees to submit all 
manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect 
proprietary information and provide comments. 
•
The sponsor will comply with the requirements for publication of study results. In
accordance with standard editorial and ethical practice, the sponsor will generally
support the publication of multicenter studies only in their entirety and not as
individual site data. In this case, a coordinating investigator will be designated by
mutual agreement.
•
Authorship will be determined by mutual agreement and in line with International
Committee of Medical Journal Editors authorship requirements.


Protocol Amendment 4 
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Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 64 of 67 
Appendix 6: Schedule of Assessments 


Protocol Amendment 4 
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Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 65 of 67 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3
(or -5 if
needed for 
COVID-19 
testing) 1 
-2
(or -4 if 
needed for 
COVID-19 
testing) 1 
-1
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
Demographics 
X 
Medical history 
X 
Admission to clinical 
research unit1 
X 
Discharge from clinical 
research unit2  
X 
Randomization 
X 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height/weight/BMI 
X 
Physical exam 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
Clinical chemistry  
(including cholesterol 
panel tests) 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, 
or HCVAb 
X 


Protocol Amendment 4 
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Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 66 of 67 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3
(or -5 if
needed for 
COVID-19 
testing) 1 
-2
(or -4 if 
needed for 
COVID-19 
testing) 1 
-1
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
12-lead safety 
electrocardiogram4,8
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cardiac Telemetry 
Monitoring9 
X 
X 
X 
(Day 
3) 
X 
 (Day 7) 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
X 
X 
X 
X 
X 
Pregnancy test6 
X 
X 
X 
Follicle -stimulating 
hormone test 
(postmenopausal females 
only) 
X 
CBP-307/placebo 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
Moxifloxacin/placebo 
administration 
X 
X 
Blood sampling for PK7,8 
X 
X 
X 
X 
X 
X 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


Protocol Amendment 4 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 5.0, 12 January 2022 
Page 67 of 67 
Abbreviations: BMI = body mass index; COVID-19 = Coronavirus Disease 2019; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C 
virus antibodies; HIV = human immunodeficiency virus; PK = pharmacokinetic. 
1.
Subjects will be asked to arrive at the clinical site in the afternoon 2 to 4 days before start of dosing on Day 1 (on Day -4 or Day -2 depending on the clinical site’s
requirements for COVID-19 testing).
2.
Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19.
3.
Screening and Check-in:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 18, and 19): Prior to and
2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: Tympanic temperature, respiratory rate,
and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to discharge, supine vital signs (tympanic temperature,
pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): Tympanic temperature, respiratory rate, and supine pulse rate and
blood pressure.
4.
12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before discharge on
Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.
5.
Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1,
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. The ECG effects
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 (supratherapeutic
concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 16.
6.
Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed at check-in (Day -4 or Day -2) and at the follow-up visit (Day 29±2
days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.
7.
Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16).
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15.
8.
Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 hour postdose, ±15 minutes for ECGs and vital
sign measurements at 2 hours postdose and ±5 minutes for PK sampling at 2 hours postdose, ±5 minutes for 3 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose,
and ±30 minutes for 12 to 24, 72, and 96 hours postdose.
9.
Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 12 hours
postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended if necessary. The
start and stop date and time of the telemetry monitoring will be recorded in the eCRF.


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 1 of 10 
Summary of Amended Protocol Changes 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Protocol Amendment 3 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Protocol Amendment 2 Date: 03 August 2021 
Protocol Amendment 3 Date: 26 October 2021 
Protocol Version: 4.0 
Investigational Medicinal Product: CBP-307 
Protocol Reference Number: CBP-307AU002 
Covance Study Number: 8463245 
IND Number: 134585 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Sites: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Clinical Pharmacology of Miami (CPMI), 
LLC 
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Sponsor Signatory: 
Ping Li, MD 
Principal Investigators: 
Nicholas Farinola, MBBS 
CMAX 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 
________________________________________ 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021  
Page 2 of 10 
The primary changes in this amendment, along with the rationale for each change as 
appropriate, are: 
1. Based on recommendations from the regulatory agency, the protocol was modified to add 
baseline QTc as a fixed effect in the concentration-QTc model and a period effect (i.e., 
Day effect) to the mixed model for moxifloxacin by-timepoint analysis so that the 
analysis will be appropriate for the crossover design of the moxifloxacin and placebo 
parts of the study. 
2. To update the protocol to modify Inclusion Criterion 6a regarding electrocardiogram 
findings for heart rate. The allowable range for heart rate was changed from 60 to 
100 bpm to 55 to 100 bpm. 
3. To modify the number of sites enrolling subjects in the study to include an additional site 
in the United States. As a result, the regulatory and contact information was revised to 
include the Institutional Review Board (IRB), Investigator, and clinical laboratory in the 
United States. Revised serious adverse event reporting as needed. Removed mention of 
the specific pharmacy for the site in Australia as there will be a pharmacy at each of the 
sites. 
4. Revised the bioanalytical laboratory contracted to perform the analysis for the study. 
5. Updated title to reflect the modification from a single site to multiple sites. 
6. To modify the pharmacokinetic endpoints to remove the accumulation ratios. 
Minor changes: 
1. The protocol version and date were updated throughout the protocol. 
2. Typographical errors and formatting errors were corrected, as necessary. 
A detailed summary of changes is presented below: 
Synopsis and Title Page, Title 
Previously read:  
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in Healthy 
Subjects 
Now reads:  
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in Healthy 
Subjects 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021  
Page 3 of 10 
Synopsis and Section 3.1, Study Design, first paragraph 
Previously read:  
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female subjects. 
Now reads:  
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female subjects. 
Study Identification Section (pages 5 and 6), Study Sites, Principal Investigators, and Clinical 
Laboratories (Title page now includes shared content from this page) 
Previously read:  
Study Site  
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Principal Investigator 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 
Clinical Laboratory  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 
Bioanalytical Laboratory 
Peter Tapley 
Director, TetraQ 
The University of Queensland 
Level 7, Block 6, RBWH 
Herston, Queensland 4029  
Australia 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021  
Page 4 of 10 
Now reads:  
Study Sites  
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
 
CPMI, LLC  
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Principal Investigators 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC 
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Tel: 1-305-817-2900 
Email: jrondon@ergclinical.com 
Clinical Laboratories  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 
 
Ecco Lab Group 
8370 West Flagler Street, Suite 216 
Miami, Florida 33144 
United States 
Tel:  1-305-220-3805 
Bioanalytical Laboratory 
Margaret Mathews 
Director  
Agilex Biolabs 
28 Dalgleish Street 
Thebarton, South Australia 5031 
Australia 
 


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Section 4.1, Inclusion Criterion 6a 
Previously read: 
Normal sinus rhythm (HR between 60 bpm and 100 bpm inclusive) 
Now reads: 
Normal sinus rhythm (HR between 55 bpm and 100 bpm inclusive) 
Section 4.5 and Appendices 1 and 5, added institutional review board (IRB; where applicable).  
Previously read:  
ethics committee (EC) or human research ethics committee (HREC) 
Now reads:  
institutional review board (IRB)/ethics committee (EC) or institutional review board 
(IRB)/human research ethics committee (HREC) 
Section 5.6, Drug Accountability, paragraph 3 
Previously read: 
At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the study 
site’s pharmacy, per the sponsor’s written instructions. If destruction is authorized to take place 
at the study site’s pharmacy (RAH Pharmacy), the investigator must ensure that the materials are 
destroyed in compliance with applicable environmental regulations and institutional policy. All 
study drug destructions must be adequately documented. 
Now reads: 
At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the study 
site’s pharmacy, per the sponsor’s written instructions. If destruction is authorized to take place 
at the study site’s pharmacy, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations and institutional policy. All study drug 
destructions must be adequately documented. 
Section 8.3, Cardiodynamic ECG Analyses, Baseline for Cardiodynamic ECG Assessments 
(where applicable) 
Previously read:  
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus placebo 
in Groups 2A and 2B) will be time-matched values on Day -1.  


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For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1, baseline will be Day 16, on which 
subjects are administered placebo. For placebo-correction in this group, placebo values 
will be derived from Day 15 on which subjects are administered placebo, and baseline 
will be obtained on Day -1. 
• Group 2B: For moxifloxacin administered on Day 16, baseline will be Day 1, on which 
subjects are administered placebo. For the placebo-correction in this group, Day -1 values 
will be used as placebo (no treatment) and baseline will be obtained on Day 15. 
Now reads:  
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus placebo 
in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1 (defined as Period 1 Day 1), baseline 
will be Day 16 (defined as Period 1 Day -1), on which subjects are administered placebo. 
For placebo-correction in this group, placebo values will be derived from Day 15 
(defined as Period 2 Day 1) on which subjects are administered placebo, and baseline will 
be obtained on Day -1 (defined as Period 2 Day -1). 
• Group 2B: For moxifloxacin administered on Day 16 (defined as Period 2 Day 1), 
baseline will be Day 1 (defined as Period 2 Day -1), on which subjects are administered 
placebo. For the placebo-correction in this group, Day -1 (defined as Period 1 Day 1) 
values will be used as placebo (no treatment) and baseline will be obtained on Day 15 
(defined as Period 1 Day -1). 
Section 8.3, Cardiodynamic ECG Analyses, Concentration-QTc Analysis (Primary Analysis), 
first paragraph. 
Previously read:  
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as the 
dependent variable, time-matched concentrations of CBP-307 as the exploratory variate (0 for 
placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on Days 1, 6, 
and 15 categorical) as fixed effects, and a random intercept and slope per subject.6  
Now reads:  
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as the 
dependent variable, time-matched concentrations of CBP-307 as the exploratory variate (0 for 
placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on Days 1, 6, 


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and 15 categorical) as fixed effects, and a random intercept and slope per subject.6 Centered 
baseline QTcF (i.e., baseline QTcF for individual subject minus the population mean baseline 
QTcF for all subjects) will be included in this model as an additional covariate. If necessary, a 
sensitivity analysis will be performed using the model without this term. 
Section 8.3, Cardiodynamic ECG Analyses, By-Timepoint Analysis, paragraphs 1 and 2 
Previously read:  
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP 307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 
time-by-treatment interaction as fixed effects. An unstructured covariance matrix will be 
specified for the repeated measures at postdose timepoints within subjects. If the model with 
unstructured covariance matrix fails to converge, other covariance matrices such as compound 
symmetry and autoregressive will be considered. From this analysis, the LS mean, SE, and 2-
sided 90% CIs will be calculated for the contrast “CBP-307 versus placebo” for each day of 
Days 1, 6, and 15 at each postbaseline timepoint on Days 1, 6, and Day 15, respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo at 
postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used with 
ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 16: 
categorical), treatment (moxifloxacin and placebo), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. An unstructured 
covariance matrix will be specified for the repeated measures at postbaseline timepoints for 
subject within visit. The model will also include a subject-specific random effect. If the model 
with an unstructured covariance matrix fails to converge, other covariance matrices, such as 
compound symmetry or autoregressive, will be considered. From this analysis, the LS mean, SE, 
and 2-sided 90% CIs will be calculated for the contrast “moxifloxacin versus placebo” at each 
postbaseline timepoint, respectively. 
Now reads:  
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 
time-by-treatment interaction as fixed effects. Baseline QTcF will be included in this model as 
an additional covariate. If necessary, a sensitivity analysis will be performed using the model 
without this term. An unstructured covariance matrix will be specified for the repeated measures 
at postdose timepoints within subjects. If the model with unstructured covariance matrix fails to 
converge, other covariance matrices such as compound symmetry and autoregressive will be 
considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs will be calculated for the 
contrast “CBP-307 versus placebo” for each day of Days 1, 6, and 15 at each postbaseline 
timepoint on Days 1, 6, and Day 15, respectively. 


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The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo at 
postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used with 
ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 16: 
categorical), treatment (moxifloxacin and placebo), period (as described in baseline definition for 
assay sensitivity), sequence (placebo/moxifloxacin or moxifloxacin/placebo), and 
time-by-treatment interaction as fixed effects. Baseline QTcF will be included in this model as 
an additional covariate.  If necessary, a sensitivity analysis will be performed using the model 
without this term. An unstructured covariance matrix will be specified for the repeated measures 
at postbaseline timepoints for subject within visit. The model will also include a subject-specific 
random effect. If the model with an unstructured covariance matrix fails to converge, other 
covariance matrices, such as compound symmetry or autoregressive, will be considered. From 
this analysis, the LS mean, SE, and 2-sided 90% CIs will be calculated for the contrast 
“moxifloxacin versus placebo” at each postbaseline timepoint on Day 1, respectively. 
Section 8.4 Pharmacokinetic Analyses, accumulation ratio 
Previously read:  
• Accumulation ratio (Rac) for Cmax (Rac[Cmax]) and Rac(AUC0-24), calculated as Day 15 
Cmax/Day 7 Cmax and Day 15 AUC0-24/Day 7 AUC0-24, respectively. 
Now reads:  
(removed) 
Appendix 1, Adverse Event Reporting, Serious Adverse Event Reporting, Contact Information 
(where applicable) 
Previously read:  
The investigator will complete an SAE report form and forward it by facsimile or email to 
Labcorp APAC Drug Safety and the sponsor immediately (within 24 hours) upon becoming 
aware of an SAE. 
All SAEs must be reported immediately (within 24 hours of discovery) to: +61-2-8879-2000 
SAE Reporting email: SAEIntake@labcorp.com (preferred method) 
Labcorp Safety SAE Reporting Fax Number: 61-2-6100-9788 or 1800-882-203 (toll free) 
The responsibilities of Labcorp APAC Drug Safety include the following: 
• Prepare an AE reporting plan prior to the start of the study. Where this plan differs from 
the applicable study site standard operating procedure on SAE reporting, the safety 
management plan will always take precedence. 
• Receive and review SAE report forms from the study site and inform the sponsor of the 
SAE within 1 working day of the initial notification to Labcorp APAC Drug Safety who 
will delete any information from the SAE report forms that may identify the subject. 


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• Write case narratives and enter the case into Labcorp’s safety database as defined in the 
AE reporting plan. 
• Produce appropriate reports of all suspected unexpected serious adverse reactions and 
forward them to the EC, Medicines and Healthcare Products Regulatory Agency, 
principal investigator, and the sponsor within the timeframes stipulated in the Clinical 
Trials Directive Guideline (ENTR/CT 3).  
Now reads:  
The investigator will complete an SAE report form and forward it by facsimile or email to 
Labcorp Drug Safety and the sponsor immediately (within 24 hours) upon becoming aware of an 
SAE. 
All SAEs must be reported immediately (within 24 hours of discovery) to:  
+61-2-8879-2000 (AUS) or 1-888-887-8097 (US) 
SAE Reporting email: SAEIntake@labcorp.com (preferred method) 
Labcorp Safety SAE Reporting Fax Numbers: 61-2-6100-9788 or 1800-882-203 (toll free) in 
Australia and 1-888-887-8097 (toll free) in the US 
The responsibilities of Labcorp Drug Safety include the following: 
• Prepare an AE reporting plan prior to the start of the study. Where this plan differs from 
the applicable study site standard operating procedure on SAE reporting, the safety 
management plan will always take precedence. 
• Receive and review SAE report forms from the study site and inform the sponsor of the 
SAE within 1 working day of the initial notification to Labcorp Drug Safety who will 
delete any information from the SAE report forms that may identify the subject. 
• Write case narratives and enter the case into Labcorp’s safety database as defined in the 
AE reporting plan. 
• Produce appropriate reports of all suspected unexpected serious adverse reactions and 
forward them to the IRB/EC, Medicines and Healthcare Products Regulatory Agency, 
FDA, principal investigator, and the sponsor within the timeframes stipulated in the 
Clinical Trials Directive Guideline (ENTR/CT 3).  
Appendix 5, Regulatory, Ethical, and Study Oversight Considerations, Data Quality Assurance, 
last bullet point  
Previously read: 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator in the study site archive for at least 5 years after the 
end of the study unless local regulations or institutional policies require a longer retention 
period. No records may be destroyed during the retention period without the written 
approval of the sponsor. No records may be transferred to another location or party 
without written notification to the sponsor.  


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Now reads: 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator in the study site archive in accordance with 21 CFR 
312.62(c) or for at least 5 years after the end of the study unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed 
during the retention period without the written approval of the sponsor. No records may 
be transferred to another location or party without written notification to the sponsor.  
 


TITLE PAGE 
Protocol 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, 
Placebo- and Positive-Controlled Study to Investigate the Effects of 
CBP-307 on the QTC Interval in Healthy Subjects 
Protocol Amendment 3 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Protocol Amendment 2 Date: 03 August 2021 
Protocol Amendment 3 Date: 26 October 2021 
Protocol Version: 4.0 
Investigational Medicinal Product: CBP-307 
 
Protocol Reference Number: CBP-307AU002 
Labcorp Study Number: 8463245 
IND Number: 134585 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Sites: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
 
Clinical Pharmacology of Miami (CPMI), 
LLC 
550 West 84th Street 
Hialeah, Florida 33014 
United States  
Sponsor Signatory: 
Ping Li, MD 
Principal Investigators: 
Nicholas Farinola, MBBS 
CMAX 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


Protocol Amendment 3 
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Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021  
Page 2 of 67 
SPONSOR APPROVAL 
I have read the protocol and approve it: 
 
 
 
 
 
 
 
Ping Li, MD 
 
Date 
VP, Clinical Development Asia 
( 
DocuSigned by: 
I *~ 
l(J 
1': 1', if 1', t/F : Ping Li 
I 
1,:1',J]li:i!i : ~jjt,t1Jt:itt!i 
~1',esffa]: 26 10Fl 2021 15:41:42 Tl:f PDT 
C::4cs56BD566CD4EA4B8BFEB77ED35D596 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245  
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021  
Page 3 of 67 
INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
 
 
 
 
 
 
 
Nicholas Farinola, MBBS 
 
Date 
Principal Investigator 
CMAX 
 
 
r;;::i~by: 
ll(J 
Signer Name: Nicholas Farinola 
L
Signing Reason: I approve this document 
Signing Time: 26 Oct 2021 110:09:12 PM PDT 
41E77C67C07F4FF8811CE7A5D4536EB8 


Protocol Amendment 3 
Labcmp Study: 8463245 
CONFIDENTIAL 
Protocol Reference: CBP-307AU002 
INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
Principal Investigator 
CPMI,LLC 
Protocol Version 4.0, 26 October 2021 
Date 
Page 4 of 67 


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Protocol Version 4.0, 26 October 2021 
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STUDY IDENTIFICATION 
Sponsor 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu 215400 
China 
Sponsor’s Study Contact 
Max Meng, BS 
Project Manager 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Tel: +86 0512 5357 7866 
Email: yhmeng@connectpharm.com 
Sponsor’s Medical Contact 
Suni Valasseri, MD 
Labcorp Clinical Research Unit Limited. 
Maidenhead 
United Kingdom 
Tel: +44 (0) 113 301 3650 
Email: S.Valasseri @labcorp.com 
Study Sites 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
CPMI, LLC  
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Principal Investigators 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 


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Protocol Version 4.0, 26 October 2021  
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Juan Carlos Rondon, MD, JD, CPI, FCLM 
CPMI, LLC  
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Tel: 1-305-817-2900 
Email: jrondon@ergclinical.com 
Clinical Laboratories  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 
 
Ecco Lab Group 
8370 West Flagler Street, Suite 216 
Miami, Florida 33144 
United States 
Tel:  1-305-220-3805 
Bioanalytical Laboratory 
Margaret Mathews 
Director  
Agilex Biolabs 
28 Dalgleish Street 
Thebarton, South Australia 5031 
Australia 
Statistician 
Wei Xiao, MS 
Labcorp Drug Development, Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 


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SYNOPSIS 
Study Title 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the pharmacokinetics (PK) of CBP-307 following administration of 
therapeutic and supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on heart rate (HR), PR and QRS intervals, and T-wave morphology. 
Study Design 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only serious 
adverse events (SAEs) will be reported. After placebo administration to all subjects on 
Day -1, all adverse events (AEs), whether volunteered, elicited, or noted upon physical 
examination, will be recorded throughout the study (ie, from Day -1 until the end of the 
study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 


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Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic electrocardiogram (ECG) monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 6, 15, 
and 16 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15. Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 


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supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
Number of Subjects 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Diagnosis and Main Criteria for Inclusion 
Healthy male and female subjects aged between 18 and 60 years (inclusive) with a body mass 
index between 18.0 and 30.0 kg/m2 (inclusive). 
Investigational Medicinal Products, Dose, and Mode of Administration 
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 titrated to 0.1 mg on 
Day 2; oral capsule) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6; oral capsule) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15; oral capsule) 
• Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 
• Moxifloxacin (400 mg; oral tablet). 


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Duration of Subject Participation in the Study 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3), 21 days for the in-house 
treatment period (Days -2 to 19), and 10 ±2 days for follow-up (Day 29±2 days), in total 
approximately 59 days. 
Endpoints 
Electrocardiogram (Cardiodynamic): 
The primary cardiodynamic endpoint is the change-from-baseline QTcF (ΔQTcF). 
The secondary cardiodynamic endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
Pharmacokinetics: 
Blood samples will be collected for the analysis of plasma concentrations of CBP-307. The 
PK parameters of CBP-307 will be calculated using a model independent approach. The 
following PK parameter endpoints will be calculated: maximum observed concentration 
(Cmax), area under the concentration-time curve from time zero extrapolated to infinity 
(AUCinf), area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24), and time of the maximum observed concentration (tmax). Other noncompartmental 
parameters may be reported. 
Safety: 
Adverse events, clinical laboratory evaluations (hematology, clinical chemistry, urinalysis), 
12lead ECGs, and vital signs measurements. 
Statistical Methods 
Cardiodynamic evaluation: 
The primary analysis will be based on concentration-QTc modeling of the relationship 
between plasma concentrations of CBP-307 and change-from-baseline QTcF (∆QTcF) with 
the intent to exclude an effect of placebo-corrected ΔQTcF (ΔΔQTcF) > 10 msec at clinically 
relevant plasma levels. Placebo-corrected ΔHR, ΔPR, ΔQRS, and ∆QTcF (ΔΔHR, ΔΔPR, 
ΔΔQRS, and ∆∆QTcF) will also be evaluated at each postdosing timepoint ('by-timepoint' 


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analysis). An analysis of categorical outliers will be performed for changes in HR, PR, QRS, 
QTcF, T-wave morphology, and U-wave presence. Assay sensitivity will be evaluated by 
concentration-QTc analysis of the effect on ∆ΔQTcF of moxifloxacin using a similar model 
as for the primary analysis. 
Pharmacokinetics: 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, standard deviation, median, 
minimum, maximum geometric mean, and geometric coefficient of variation) separately by 
cohort. Individual and mean plasma CBP-307 and moxifloxacin concentration versus time 
data will be tabulated and plotted by dose level. Graphical displays of PK data may be 
provided as well.  
Pharmacokinetic/electrocardiography analyses: 
The relationship between CBP-307 plasma concentrations and the change from ∆QTcF will 
be evaluated using a linear mixed-effects modeling approach. 
Safety: 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12lead ECGs, vital signs, and physical 
examination findings will be listed. 


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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SPONSOR APPROVAL ...........................................................................................................2 
INVESTIGATOR AGREEMENT.............................................................................................3 
INVESTIGATOR AGREEMENT.............................................................................................4 
STUDY IDENTIFICATION .....................................................................................................5 
SYNOPSIS .................................................................................................................................7 
TABLE OF CONTENTS .........................................................................................................12 
LIST OF TABLES AND FIGURES........................................................................................15 
LIST OF ABBREVIATIONS ..................................................................................................16 
1. 
INTRODUCTION ...........................................................................................................18 
1.1. 
Disease Background...............................................................................................18 
1.2. 
Overview of CBP-307............................................................................................18 
1.2.1. 
Summary of Clinical Experience .................................................................18 
1.2.1.1. 
Safety .................................................................................................19 
1.2.1.2. 
Pharmacokinetics ...............................................................................21 
1.3. 
Overview of Moxifloxacin .....................................................................................22 
1.4. 
Study Rationale ......................................................................................................22 
1.5. 
Benefit-risk Assessment.........................................................................................23 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................23 
2.1. 
Objectives ..............................................................................................................23 
2.2. 
Endpoints ...............................................................................................................23 
2.2.1. 
Electrocardiogram Endpoints .......................................................................23 
2.2.1.1. 
Primary ...............................................................................................23 
2.2.1.2. 
Secondary ...........................................................................................23 
2.2.2. 
Pharmacokinetic Endpoints .........................................................................24 
2.2.3. 
Safety Endpoints ..........................................................................................24 
3. 
INVESTIGATIONAL PLAN ..........................................................................................24 
3.1. 
Overall Study Design and Plan ..............................................................................24 
3.2. 
Discussion of Study Design ...................................................................................27 
3.3. 
Selection of Doses in the Study .............................................................................27 
4. 
SELECTION OF STUDY POPULATION .....................................................................28 
4.1. 
Inclusion Criteria ...................................................................................................28 
4.2. 
Exclusion Criteria ..................................................................................................28 
4.3. 
Subject Number and Identification ........................................................................31 
4.4. 
Subject Withdrawal and Replacement ...................................................................31 
4.5. 
Study Termination .................................................................................................32 
5. 
STUDY TREATMENTS .................................................................................................32 
5.1. 
Investigational Products .........................................................................................32 


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5.2. 
Study Treatment Administration............................................................................34 
5.3. 
Randomization .......................................................................................................34 
5.4. 
Blinding..................................................................................................................35 
5.5. 
Treatment Compliance ...........................................................................................35 
5.6. 
Drug Accountability...............................................................................................35 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................36 
6.1. 
Concomitant Therapies ..........................................................................................36 
6.2. 
Diet .........................................................................................................................36 
6.3. 
Smoking .................................................................................................................37 
6.4. 
Exercise ..................................................................................................................37 
6.5. 
Blood Donation ......................................................................................................37 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................37 
7.1. 
General Assessments .............................................................................................38 
7.1.1. 
Demographics ..............................................................................................38 
7.1.2. 
Medical History ...........................................................................................38 
7.2. 
Electrocardiography Assessments .........................................................................38 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording ......................................38 
7.2.1.1. 
TQT Plus Extraction Technique ........................................................38 
7.2.1.2. 
Expert Precision QT Analysis ............................................................39 
7.2.2. 
Safety 12-lead Electrocardiogram ................................................................39 
7.2.3. 
Cardiac Telemetry Monitoring ....................................................................40 
7.3. 
Pharmacokinetic Assessments ...............................................................................40 
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................40 
7.3.2. 
Analytical Methodology ..............................................................................40 
7.4. 
Safety and Tolerability Assessments .....................................................................40 
7.4.1. 
Adverse Events ............................................................................................40 
7.4.2. 
Clinical Laboratory Evaluations ..................................................................41 
7.4.3. 
Vital Signs ....................................................................................................41 
7.4.4. 
Physical Examination...................................................................................41 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................42 
8.1. 
Determination of Sample Size ...............................................................................42 
8.2. 
Analysis Populations ..............................................................................................43 
8.2.1. 
Cardiodynamic Population...........................................................................43 
8.2.2. 
Pharmacokinetic Population ........................................................................43 
8.2.3. 
Safety Population .........................................................................................43 
8.3. 
Cardiodynamic ECG Analyses ..............................................................................43 
8.4. 
Pharmacokinetic Analyses .....................................................................................47 
8.5. 
Safety Analysis ......................................................................................................47 
8.6. 
Interim Analysis .....................................................................................................47 


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9. 
REFERENCES ................................................................................................................48 
10. APPENDICES .................................................................................................................49 
Appendix 1: Adverse Event Reporting ..............................................................................50 
Appendix 2: Clinical Laboratory Evaluations ...................................................................55 
Appendix 3: Total Blood Volume......................................................................................56 
Appendix 4: Contraception Guidance ................................................................................57 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations ............................60 
Appendix 6: Schedule of Assessments ..............................................................................64 
 


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LIST OF TABLES AND FIGURES 
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................21 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................22 
Table 3: Study Treatments .................................................................................................33 
 
Figure 1: Study Schematic .................................................................................................25 
 


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LIST OF ABBREVIATIONS 
Abbreviation Definition 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUCinf 
area under the concentration-time curve from time zero extrapolated to 
infinity 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours 
postdose 
CI 
confidence interval 
CL/F 
apparent total clearance 
Cmax 
maximum observed concentration 
CRO 
contract research organization 
CYP 
cytochrome P450 
Δ 
change-from-baseline 
ΔΔ 
placebo-corrected or placebo-adjusted change-from-baseline 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
HR 
heart rate 
HREC 
human resource ethics committee 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
IP 
investigational product 
IRB 
institutional review board 
LOESS 
locally estimated scatterplot smoothing 
LS 
least squares 
PK 
pharmacokinetic(s) 
PD 
pharmacodynamic(s) 
QD 
once daily 
QTc 
heart-corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
 
 


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SAE 
serious adverse event 
SD 
standard deviation 
SE 
standard error 
S1P1 
sphingosine-1-phosphate receptor 1 
TEAE 
treatment-emergent adverse event(s) 
t1/2 
apparent terminal elimination half-life 
tmax 
time of the maximum observed concentration 
TQT 
thorough QT 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
λZ 
apparent terminal elimination rate constant 
 
 


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1. INTRODUCTION 
Refer to the investigator’s brochure (IB)1 for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile 
of the investigational medicinal product (IMP). 
1.1. 
Disease Background 
Autoimmune diseases are serious disorders that afflict a large portion of the world 
population; most have no cures. Significant advances have been made in the development of 
novel and disease-modifying therapies, but many of these new treatments have significant 
side effects. Treatments are needed that provide better risk-to-benefit profiles than the 
existing therapeutic choices. 
T cells are important immune cells that mediate the development of autoimmune disorders. 
Migration of T cells from lymphoid tissues to the sites of inflammation is central to the 
functions of T cells, and this process is dependent on sphingosine-1-phosphate (S1P) receptor 
1 (S1P1) which is known to ameliorate a variety of autoimmune diseases in animals and 
humans. Down modulation of this receptor, using S1P1 agonists, prevents T cell egress and 
results in a reduced number of circulating lymphocytes, particularly the CD4+- and CD8+-
naïve and central-memory T cell subsets.  
1.2. 
Overview of CBP-307 
CBP-307 is an S1P1 agonist that is being developed as a treatment for autoimmune diseases 
by Suzhou Connect Biopharmaceuticals, Ltd. CBP-307 (1-(2-fluoro-4-(5-(4-isobutylphenyl)-
1,2,4-oxadiazol-3-yl) benzyl) azetidine-3-carboxylic acid hemihydrate) is a potent, selective, 
small-molecule agonist of S1P1 and S1P5 receptors. Cell-based assays have confirmed 
CBP-307 induces internalization of S1P1 from the cell surface. This is consistent with the 
known mechanism of action of other S1P1 agonists, in that they down-modulate S1P1 and 
inhibit lymphocyte egress from lymphoid tissues.  
1.2.1. 
Summary of Clinical Experience 
The Phase 1 development of CBP-307 comprised 2 completed studies in healthy subjects: 
• A single and multiple ascending dose study to evaluate the safety and tolerability of 
CBP-307 including pharmacokinetic (PK), pharmacodynamic (PD), and food-effect 
assessments (Study CBP-307AU001) 
• A single-dose and multiple-dose, and fixed-dose titration study to evaluate the safety 
and tolerability of CBP-307 including PK and PD (Study CBP-307CN001) 
Currently, CBP-307 is being evaluated in 2 Phase 2 studies:  
• Ongoing multicenter study in subjects with moderate to severe ulcerative colitis 
(Study CBP-307CN002) to compare the clinical efficacy by evaluating the clinical 
response to CBP-307 versus placebo and the clinical remission and mucosal healing 


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achieved by CBP-307 versus placebo and to compare the clinical safety and 
tolerability of CBP-307 with those of placebo. 
• Ongoing study in subjects with moderate to severe Crohn’s disease compares clinical 
efficacy by evaluating the clinical response to CBP-307 versus placebo and the 
clinical remission and mucosal healing achieved by CBP-307 versus placebo and to 
compare the clinical safety and tolerability of CBP-307 with those of placebo. 
1.2.1.1. 
Safety 
Study CBP-307AU001 
A total of 44 healthy subjects were enrolled in the study. There were 28 subjects evaluated 
using the single-dose regimen (0.1, 0.25, 0.5, and 2.5 mg CBP-307) of which 21 subjects 
received CBP-307 and 7 subjects received placebo. Another 16 healthy subjects were 
evaluated using the multiple-dose regimen (0.15 and 0.25 mg CBP-307 given once daily 
[QD] for 28 consecutive days) of which 12 subjects received CBP-307 and 4 subjects 
received placebo. 
Overall, no unexpected safety signals were identified and no deaths occurred in this study. 
For the single-dose regiment, no subjects were discontinued due to a treatment-emergent AE 
(TEAE). In the multiple-dose regimen, there were 2 subjects who were discontinued from the 
study (due to increased alanine transaminase and second degree AV block [not considered to 
be clinically significant, as judged by the investigator]). All TEAEs resolved by the end of 
the study. 
In the single-dose regimen groups, TEAEs were reported in 12 of 21 subjects (57.1%) treated 
with CBP-307 and in 3 of 7 subjects (42.8%) treated with placebo. Most (91.7%) of the 
TEAEs in these subjects were mild in severity. The most common TEAEs in the 
CBP-307-treated groups were headache (28.6%); dizziness (19.0%); and bradycardia (9.5%). 
Bradycardia was reported only in 2 subjects receiving the highest (2.5 mg) CBP-307 dose. 
One subject had a serious adverse event (SAE) of bradycardia (associated with transient 
asystole) following a single dose of 2.5 mg CBP-307. 
In the multiple-dose regimen groups, CBP-307 at doses of 0.15 and 0.25 mg QD was 
generally well tolerated over the 28 days of dosing. Treatment-emergent AEs were reported 
in 11 of 12 subjects (91.7%) in the CBP-307 groups and 2 of 4 subjects (50.0%) in the 
placebo groups. Most (83.3%) TEAEs were mild in severity. The most common TEAEs in 
the 2 CBP-307 groups were headache (50.0%), and fatigue, nausea, and musculoskeletal pain 
(16.7% each). The incidences of these TEAEs were similar in both CBP-307-treated groups. 
No SAEs were reported for subjects in the multiple-dose regimen. 
Study CBP-307CN001 
A total of 30 eligible subjects completed 3 CBP-307 dose groups in ascending order of dose 
after randomization (in a ratio of 1:1:1): Group A (0.1 mg), Group B (0.2 mg), and Group C 
(0.3 mg). Each dose group consisted of 10 subjects, including 8 subjects receiving the 
investigational drug and 2 subjects receiving placebo by random assignment. The 
administration started from the dose of 0.1 mg. The subjects in this group received a single 


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dose of CBP-307 or placebo and were followed up for safety and tolerance within the next 
7 days. Then the subjects received 0.1 mg CBP-307 or placebo QD for 14 consecutive days 
and were followed up for safety and tolerance within the next 7 days. Dose escalation did not 
occur until the review of the single-dose regimen safety data from the 6 subjects in the 
previous dose cohort, and the safety data did not meet the termination criteria. The subjects in 
the dose of 0.3 mg received fixed-dose titration regimen, ie, 0.05 mg CBP-307 or placebo QD 
for 3 consecutive days; 0.1 mg CBP-307 or placebo QD for 2 consecutive days; 0.2 mg 
CBP-307 or placebo QD for 2 consecutive days; finally, 0.3 mg CBP-307 or placebo QD for 
14 consecutive days, and the subjects were followed up for safety and tolerance within the 
next 7 days. 
Overall, no unexpected safety signals were identified, and there were no deaths, SAEs, or 
AEs leading to the subject’s early withdrawal from the study after administration of 
CBP-307. In the safety set, a total of 29 subjects (8 in Group A, 100%; 8 in Group B, 100%; 
8 in Group C, 100% and 5 in placebo group, 83.3%) experienced TEAEs. 
During the single-dose period, a total of 14 subjects (5 of 8 in Group A, 62.5%; 6 of 8 in 
Group B, 75%, and 3 of 4 in placebo group, 75%) developed AEs. The incidence of TEAEs 
in Group A was generally similar to the placebo group. Among TEAEs in Group B, the 
incidence of AEs related to abnormalities in investigations was higher than that in placebo 
group, including lymphocyte count decreased (12.5%), white blood cell (WBC) count 
decreased (12.5%), neutrophil count decreased (12.5%), alanine aminotransferase increased 
(25%), and gamma-glutamyltransferase increased (12.5%), and aspartate aminotransferase 
increased (12.5%). Additionally, 1 subject experienced heart rate (HR) decreased (12.5%). 
During dose-titration period, 2 subjects (2 of 8 in Group C, 25%) experienced TEAEs. The 
TEAEs reported in Group C during the titration period included cough (12.5%) and increased 
upper airway secretion (12.5%). There were no TEAEs in the placebo group during this 
period. 
During repeated-dose period, a total of 28 subjects (8 of 8 in Group A, 100%; 8 of 8 in Group 
B, 100%; 8 of 8 in Group C, 100%; and 4 of 6 in placebo group, 66.7%) experienced AEs. 
The most frequent TEAE in Group A was upper respiratory tract infection (37.5%) compared 
with placebo group; the most frequent TEAEs in Group B and Group C included decreased 
lymphocyte count (Group B, 87.5%; Group C, 100.0%), WBC count (Group B, 87.5%; 
Group C, 62.5%), and neutrophil count (Group B, 50%; Group C, 12.5%). The TEAEs noted 
in Group B during the repeated-dose period also included increased alanine aminotransferase 
(25%), gamma-glutamyltransferase (37.5%), and aspartate aminotransferase (12.5%), upper 
respiratory tract infection (12.5%), influenza (12.5%), chest pain (12.5%), lethargy (25%), 
and neck pain (12.5%); TEAEs in Group C during the repeated-dose period also included 
increased alanine aminotransferase (25%), decreased HR (12.5%), and mouth ulcer (12.5%); 
the TEAEs in placebo group included increased transaminase (16.7%), prolonged activated 
partial thromboplastin time (1/6, 16.7%), decreased hemoglobin (16.7%), upper respiratory 
tract infection (16.7%), diarrhea (16.7%), dizziness (16.7%), and palpitations (16.7%). 
Study CBP-307CN002 
This study is ongoing and there are no safety data available.  


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Study CBP-307CN003 
This study is ongoing and there are no safety data available.  
1.2.1.2. 
Pharmacokinetics 
CBP-307 given orally as a single dose was readily absorbed; drug concentrations peaked at 
approximately 6 hours after administration, with an elimination apparent terminal elimination 
half-life (t1/2) of approximately 25 hours (range of 23 to 29 hours). The time to maximum 
observed concentration (Cmax) in the blood was delayed from 6 hours to approximately 
10 hours when CBP-307 was given with a high-fat diet. Food consumption also increased 
exposure (Table 1). 
For the single-dose administration, CBP-307 exposure (based on Cmax and area under the 
concentration-time curve [AUCs]) increased with increasing dose following a single-dose 
administration (Table 1).  
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Single-Dose 
Regimen PK 
Parameters 
Mean CBP-307 Single Dose ± SEM (n) 
0.1 mg 
0.25 mg 
0.5 mg 
(fasted) 
0.5 mg (fed)a 
2.5 mg 
AUClast 
(ng*h/mL) 
13.4 ± 3.54 
(n = 6) 
45.1 ± 5.25 
(n = 6) 
160 ± 22.8 
(n = 6) 
290 ± 28.1 
(n = 6) 
550 ± 96.3 
(n = 3) 
AUCinf 
(ng*h/mL) 
ND 
63.7 ± 2.14 
(n = 3) 
214 ± 58.3 
(n = 3) 
355 ± 44.3 
(n = 5) 
710 ± 164 
(n = 2) 
Cmax 
(ng/mL) 
0.537 ± 0.0931 
(n = 6) 
1.53 ± 
0.0935 
(n = 6) 
4.84 ± 0.706 
(n = 6) 
8.58 ± 1.11 
(n = 6) 
19.0 ± 3.55 
(n = 3) 
tmax 
(hours) 
7.33 ± 1.33 
(n = 6) 
5.33 ± 0.99 
(n = 6) 
5.00 ± 0.86 
(n = 6) 
10.67 ± 2.72 
(n = 6) 
6.00 ± 2.00 
(n = 3) 
t1/2 
(hours) 
ND 
23.3 ± 1.70 
(n = 3) 
28.8 ± 1.28 
(n = 3) 
26.0 ± 1.17 
(n = 5) 
22.8 ± 3.96 
(n = 2) 
Abbreviations: AUCinf = area under the curve at infinity; AUClast = area under the curve at the last time point; 
Cmax = maximum concentration; h = hour(s); mg = milligram(s); ND = not determinable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SEM = standard error of the mean; T1/2 = elimination half-life; tmax = time to maximum 
concentration.  
a Study Part 1b: Cohort 3 from Part 1a returned to receive a single oral dose of CBP-307 at 0.5 mg under fed conditions. 
Source: Final report for Study CBP-307AU001. 
For the repeated-dose administration of CBP-307, the Cmax and AUCs increased with the 
higher administered dose (Table 2). At the steady-state timepoint on Day 28, the median 
CBP-307 tmax was 4 to 6 hours. The average t1/2 was similar, ranging 44 to 49 hours, and 
there were no dose-dependent changes in t1/2 within the dose range. The t1/2 was slightly 
prolonged after repeated-dose administration when compared with that after a single-dose 
administration. Moderate accumulation of CBP-307 (approximately 3 times the levels 


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following a single dose) was noted in plasma after QD administration for 14 consecutive 
days. 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Multiple-Dose 
Regimen PK 
Parameters 
Multiple-Dose Cohort 1  
CBP-307 Dosing, mg (± SD) (n) 
Multiple-Dose Cohort 2  
CBP-307 Dosing, mg (± SD) (n) 
Day 1 
0.1  
Day 28 
0.25  
Day 1 
0.15  
Day 28 
0.15  
AUC0-24 
(ng*h/mL) 
24.5 ± 3.26 
(n = 5) 
125 ± 12.4 
(n = 4) 
26.3 ± 7.45 
(n = 5) 
79.7 ± 27.3 
(n = 6) 
AUClast 
(ng*h/mL) 
NA 
203 ± 21.9 
(n = 4) 
NA 
131 ± 44.7 
(n = 6) 
Cmax 
(ng/mL) 
1.45 ± 0.214 
(n = 5) 
6.30 ± 0.588 
(n = 4) 
1.32 ± 0.422 
(n = 6) 
4.23 ± 1.45 
(n = 6) 
tmax 
(hours) 
6.80 ± 1.50 
(n = 5) 
6.50 ± 1.50 
(n = 4) 
5.00 ± 0.68 
(n = 6) 
4.33 ± 0.33 
(n = 6) 
Abbreviations:  AUC0-24 = area under the curve from time 0 to 24 hours; AUClast = area under the curve at the last time 
point; Cmax = maximum concentration; mg = milligram(s); NA = not applicable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SD = standard deviation; tmax = time to maximum concentration. 
Source: Final report for Study CBP-307AU001. 
1.3. 
Overview of Moxifloxacin 
Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic that binds to and inhibits the 
hERG IKr α subunit and causes a mean increase of the QTc interval of 6 ms after a single 
400-mg oral dose. Moxifloxacin is commonly used as a positive control in thorough QT 
(TQT) studies to satisfy the requirements of International Council for/Conference on 
Harmonisation (ICH) E14. 
Refer to the regional manufacturer package insert of AVELOX (moxifloxacin hydrochloride) 
tablets for additional information.2 
1.4. 
Study Rationale 
Regulatory guidance (ICH E14) has emphasized the need to obtain clear robust data on the 
effect of new chemical entities on electrocardiogram (ECG) parameters with focus on cardiac 
repolarization as measured by the QTc duration. Though many Phase 1, 2, and 3 trials may be 
conducted they usually have an insufficient sample size, infrequent sampling of ECG data, or 
the use of inadequate controls to overcome the high rate of spontaneous change in QTc 
duration. This has resulted in regulatory guidance recommending a dedicated or thorough 
trial to define the ECG effects of new drugs. 
This study will be done in healthy subjects to eliminate variables (concomitant drugs, 
diseases, etc.) known to have an effect on ECG parameters. A supratherapeutic dose of 
CBP-307 is required to mimic the exposure in healthy subjects that may occur in the target 
population under the worst of circumstances (eg, concomitant use of cytochrome P450 


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[CYP]3A4 inhibitor, concomitant liver disease, presence of heart disease, taking more than 
the clinical dose prescribed) and to allow for PK to QTc modeling to assess the effect of drug 
concentration on cardiac repolarization. 
1.5. 
Benefit-risk Assessment 
Healthy subjects in the current study will not receive any health benefit (beyond that of an 
assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from the collection of blood samples and other study 
procedures. More information about the known and expected benefits, risks, and reasonably 
anticipated AEs associated with CBP-307 may be found in the IB.1  
2. OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the PK of CBP-307 following administration of therapeutic and 
supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on HR, PR and QRS intervals, and T-wave morphology. 
2.2. 
Endpoints 
2.2.1. 
Electrocardiogram Endpoints 
2.2.1.1. 
Primary 
The primary endpoint is the change-from-baseline QTcF (ΔQTcF). 
2.2.1.2. 
Secondary  
The secondary endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 


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• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
2.2.2. 
Pharmacokinetic Endpoints 
Pharmacokinetic parameters of CBP-307 will be determined if data allows: 
• area under the concentration‑time curve from time zero extrapolated to infinity 
(AUCinf) 
• area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24) 
• maximum observed concentration (Cmax) 
• time of the maximum observed concentration (tmax) 
Other PK parameters may also be reported. 
2.2.3. 
Safety Endpoints 
The safety outcome measures for this study are as follows: 
• incidence and severity of AEs 
• incidence of laboratory abnormalities, based on hematology, clinical chemistry, and 
urinalysis test results 
• 12-lead ECG parameters 
• vital signs measurements. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only SAEs will be 
reported. After placebo administration to all subjects on Day -1, all AEs, whether 


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volunteered, elicited, or noted upon physical examination, will be recorded throughout the 
study (ie, from Day -1 until the end of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 
Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec.  
An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 
32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 
16 subjects. Subjects will be randomized to receive a treatment sequence that includes 4 treatments (CBP-307 therapeutic 
dose, CBP-307 supratherapeutic dose, moxifloxacin, or placebo [matched to CBP-307 or moxifloxacin]); assigned study 
treatments will be administered on Day 1, Day 2, Days 3 to 6, Days 7 to 15, and Day 16. Dosing details are provided in 
Table 3. Blood samples for pharmacokinetic analysis will be collected predose and at each postdose cardiodynamic 
electrocardiogram timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. An 
end-of-study visit will occur on Day 29±2 days. 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1
Day 2


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Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at 
least 25 hours prior to the administration of study treatments on Day 1 and continue through 
24 hours after the administration of study treatments on Days 1, 6, 15, and 16 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK 
analysis will be collected predose and at each postdose cardiodynamic ECG timepoint. 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 


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The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 
3.2. 
Discussion of Study Design 
The purpose of this study is to evaluate the potential for CBP-307 to cause QT prolongation. 
As CBP-307 exposure affects heart rate, the primary endpoint for this study will be the QTcF. 
The study will be randomized and double-blind because randomization eliminates 
confounding by baseline variables and blinding eliminates confounding by co-interventions, 
thus eliminating the possibility that the observed effects of the intervention are because of 
differential use of other treatments.  
The sample size for this study is based on a formal statistical power calculation. 
Conducting the study in healthy subjects mitigates the potential confounding effects of the 
disease state and concomitant medications. Both male and female subjects will be included to 
eliminate similar known ECG variability effects. 
Additionally, because food has been shown to alter the PK of CBP-307, subjects will be 
fasted at least 10 hours prior to dose administration and remain fasted for 4 hours postdose on 
the days when PK samples are collected. 
Pharmacokinetic assessments of CBP-307 concentrations in plasma will be evaluated during 
the study. The timepoints for the PK sample collections are based on previous studies and are 
considered adequate to allow for the characterization of the drug’s PK after oral dosing. 
Furthermore, the chosen PK sample collection for CBP-307 is anticipated to be sufficient to 
allow reasonable estimation of t1/2 during the terminal elimination phase.  
3.3. 
Selection of Doses in the Study 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To 
carefully monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 
doses will be up-titrated as follows: subjects will receive a starting dose of 0.05 mg CBP-307 
on Day 1 followed by an up-titrated dose of 0.1 mg on Day 2 and a dose of 0.2 mg on 
Days 3 to 6. Prior clinical experience with CBP-307 has not demonstrated clinically 
significant abnormalities in laboratory test results in the majority of subjects or a 
dose-response relationship for safety based on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the 
characteristics of the study design with the safety of healthy subjects. Testing of CBP-307 at 
substantial multiples of the anticipated maximum therapeutic exposure is not clinically 
warranted due to the known safety and tolerability profile of CBP-307.  


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Further details are provided in the IB.1 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the screening visit unless otherwise 
stated: 
1. Males or females, of any race, between 18 and 60 years of age, inclusive. 
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive. 
3. In good health, determined by no clinically significant findings from medical history, 
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) at screening and 
confirmed at check-in as assessed by the investigator (or designee). 
4. Females will not be pregnant or lactating, and females of childbearing potential and 
males will agree to use contraception as detailed in Appendix 4. Negative pregnancy 
test for females of childbearing potential at screening (blood test) and check-in (urine 
test). 
5. Supine diastolic blood pressure between 60 and 90 mmHg and systolic blood pressure 
between 90 and 140 mmHg (inclusive) at screening on a single measurement 
(confirmed by a single repeat, if necessary) following at least 5 minutes of rest. 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
a. Normal sinus rhythm (HR between 55 bpm and 100 bpm inclusive); 
b. QTcF interval ≤450 msec for males and females; 
c. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
d. PR interval ≤200 msec. 
7. Has serum potassium, calcium, and magnesium levels within the normal reference 
range at screening, as judged by the investigator. 
8. Able to swallow multiple tablets (based on subject’s verbal confirmation). 
9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 
4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
screening visit unless otherwise stated: 
1. Subject is mentally or legally incapacitated or has had significant history of recent 
mental health issues requiring medication and/or hospitalization at the time of the 
screening visit or expected during the conduct of the study. 


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2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, 
hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the 
investigator (or designee). Note: Childhood asthma that is considered recovered or 
seasonal allergies that are not currently active or requiring treatment are allowed. 
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, unless approved by the investigator (or designee). 
4. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, 
related compounds, or inactive ingredients. 
5. History of significant multiple and/or severe allergies (eg, latex allergy, band-aids, 
adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant 
intolerability to prescription or nonprescription drugs. 
6. History of stomach or intestinal surgery or resection that would potentially alter 
absorption and/or excretion of orally administered drugs within 6 months prior to the 
first dose of study drug (uncomplicated appendectomy and hernia repair will be 
allowed). 
7. History or presence of: 
a. Hypokalemia, in the opinion of the investigator (or designee); 
b. Risk factors for Torsades de Pointes (eg, heart failure, cardiomyopathy, or 
family history of Long QT Syndrome); 
c. Sick sinus syndrome, second, or third degree atrioventricular block, 
myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged 
QT interval, or conduction abnormalities; 
d. Repeated or frequent syncope or vasovagal episodes; 
e. Hypertension, angina, bradycardia, or severe peripheral arterial circulatory 
disorders. 
8. Clinically significant abnormalities (as judged by the investigator in laboratory tests 
results [out-of-range results confirmed on repeat]), including but not limited to the 
following parameters: 
a. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or 
total bilirubin greater than 1.5 × upper limit of normal; 
b. hemoglobin <10 g/dL, WBC <3.0 ×109/L, neutrophils <1.5 ×109/L, 
lymphocytes <0.8 ×109/L and platelets <100 ×109/L or >1200 × 109/L; 
9. History or evidence of alcoholism or drug/chemical abuse within 12 months prior to 
check-in. 
10. Alcohol consumption of >10 units per week for males and females. One unit of 
alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill 
(25 mL) of spirits. 
11. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) 
at screening or check-in.  


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12. Positive hepatitis panel, positive syphilis test, and/or positive human 
immunodeficiency virus test (Appendix 2).  
13. Participation in a clinical study involving administration of an investigational drug 
(new chemical entity) in the past 28 days prior to the first dose of study treatment on 
Day 1. The 28-day window will be derived from the date of the last blood collection 
or dosing, whichever is later, in the previous study to Day 1 of the current study. 
14. Participation in a previous clinical study where subjects received CBP-307. 
15. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 
28 days prior to first dose of study treatment on Day 1. 
16. Use or intend to use any prescription medications/products within 14 days prior to 
first dose of study drug (Day 1) and throughout the study, unless deemed acceptable 
by the investigator (or designee). Note: For females only, the use hormonal 
contraception, hormone replacement therapy or oral, implantable, transdermal, 
injectable, or intrauterine hormonal contraceptives within 14 days prior to Day 1 is 
not acceptable, except for Mirena®. 
17. Use or intend to use any drugs known to be significant inhibitors or inducers of CYP 
enzymes and/or P-gp, including St. John’s Wort, for days prior to the first dose of 
study drug and throughout the study. Appropriate sources will be consulted by the 
investigator or designee to confirm the lack of PK/PD interaction with the study drug. 
18. Use or intend to use slow-release medications/products considered to still be active 
within 14 days prior to check-in, unless deemed acceptable by the investigator (or 
designee). 
19. Use or intend to use any nonprescription medications/products including antacids, 
vitamins (especially those containing magnesium, aluminum, iron, or zinc), minerals, 
and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to 
check-in, unless deemed acceptable by the investigator (or designee). 
20. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or 
positive cotinine at screening or check-in.  
21. Has been on a diet incompatible with the on-study diet (including an extreme diet 
which resulted in a significant weight change for whatever reason), in the opinion of 
the investigator, within the 28 days prior to the first dose of study treatment, and 
throughout the study. 
22. Consumption of caffeine/xanthine-containing foods or beverages within 48 hours 
prior to check-in until discharge. 
23. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages 
within 7 days prior to check-in. 
24. Receipt of blood products within 2 months prior to check-in. 
25. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to 
screening, or platelets from 6 weeks prior to screening. 
26. Poor peripheral venous access. 


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27. Subjects who, in the opinion of the investigator (or designee), should not participate 
in this study. 
4.3. 
Subject Number and Identification 
Subjects will have a unique identification number used at screening. Eligible subjects will be 
assigned a subject number prior to the first dosing occasion. Assignment of subject numbers 
will be in ascending order and no numbers will be omitted (eg, Subjects 0101, 0102, 0103). 
The screening number will be used on all safety samples throughout the study. Replacement 
subjects (Section 4.4) will be assigned a subject number corresponding to the number of the 
subject he/she is replacing plus 1000 (eg, Subject 1101 replaces Subject 0101). 
Subjects will be identified by screening identification number or subject number only on all 
study documentation. A list identifying the subjects by subject number will be kept in the site 
master file. 
4.4. 
Subject Withdrawal and Replacement 
A subject is free to withdraw their informed consent from the study at any time or they may 
be withdrawn at any time at the discretion of the investigator or the sponsor for safety, 
behavioral, or the inability of the subject to comply with the protocol-required visits or 
procedures. In addition, a subject will be withdrawn from dosing if any of the following 
criteria are met: 
• change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the investigator (or designee) 
• noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the investigator (or designee) 
• any clinically relevant sign or symptom that, in the opinion of the investigator (or 
designee), warrants subject withdrawal. 
If a subject is withdrawn from dosing, the sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic case report form (eCRF). If 
a subject is withdrawn from the study, efforts will be made to perform all follow-up 
assessments, if possible (Appendix 6). Other procedures may be performed at the 
investigator’s (or designee’s) and/or sponsor’s discretion. If the subject is in-house, these 
procedures should be performed before the subject is discharged from the clinic. The 
investigator (or designee) may also request that the subject return for an additional follow-up 
visit. All withdrawn subjects will be followed until resolution of all their AEs or until the 
unresolved AEs are judged by the investigator (or designee) to have stabilized. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, effort should be made to document subject outcome, if possible. 
The investigator should inquire about the reason for withdrawal, request the subject to return 
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Subjects who are withdrawn for reasons not related to study treatment may be replaced 
following discussion between the investigator and the sponsor. Subjects withdrawn as a result 
of AEs thought to be related to the study treatment will generally not be replaced. 
4.5. 
Study Termination 
The study may be discontinued at the discretion of the investigator (or designee), sponsor, or 
sponsor’s medical monitor if any of the following criteria are met: 
• investigator decides to terminate the study due to safety concerns such as AEs 
unknown to date (ie, not previously reported in any similar investigational study drug 
trial with respect to their nature, severity, and/or duration) 
• increased frequency, severity, and/or duration of known, anticipated, or previously 
reported AEs (this may also apply to AEs defined at check-in as baseline signs and 
symptoms) 
• medical or ethical reasons affecting the continued performance of the study 
• difficulties in the recruitment of subjects 
• cancelation of drug development 
• sponsor requests for termination (eg, due to financial or management reasons, etc.) 
under the premise to fully protect the safety and rights of subjects  
• health authority or institutional review board (IRB)/ethics committee (EC) orders the 
termination of the trial for any reason. 
Definition of end-of-treatment and end-of-study  
• end-of-treatment is completion of safety follow-up or withdrawal from the study. 
End-of-study is the last visit by the last subject. 
5. STUDY TREATMENTS 
Study treatments are defined as any investigational product (IP), non-investigational product 
(non-IP), placebo, or medical device intended to be administered to a study subject according 
to the study protocol. 
Note that in several countries, IP and non-IP are referred to as IMP and non-IMP, 
respectively. 
5.1. 
Investigational Products 
The details regarding the storage, preparation, destruction, and administration of each 
treatment shown in Table 3 will be provided in a separate document. Approximately 
64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 
and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and 
each sub-group will be randomized with 16 subjects.  
 


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Table 3: Study Treatments 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
1 capsule 
 
1 tablet 
Group 2A 
 
1 capsule 
 
1 tablet 
Group 2B 
 
1 capsule 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
electronic 
case report 
form (eCRF). 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
 
All supplies of the IMP, both bulk and subject-specific, will be stored in accordance with the 
manufacturer’s or pharmacy’s instructions. Until dispensed to the subjects, the study 
treatments will be stored at the study site in a location that is locked with restricted access. 
5.2. 
Study Treatment Administration 
Each dose of study treatment (CBP-307, placebo, or moxifloxacin) will be administered 
orally following an overnight fast of at least 10 hours, with approximately 240 mL of room 
temperature water. Additionally, because food has been shown to alter the PK of CBP-307, 
subjects will be fasted at least 10 hours prior to dose administration and remain fasted for 
4 hours postdose on the days when PK samples are collected. 
Subjects will be dosed in numerical order while sitting or standing but not be permitted to lie 
supine for 2 hours after treatment administration, except as necessitated by the occurrence of 
an AE(s) and/or study procedures. 
5.3. 
Randomization 
This is a double-blind randomized study. Subjects will be randomized to one of the treatment 
sequences before administration of the first dose of study treatment. A randomization list will 
be generated by a statistician using a computer-generated pseudo-random permutation 
procedure. The randomization date is to be documented in the subject’s medical record and 
on the enrollment eCRF. A computer-generated randomization schedule and emergency 
code-break envelopes will be provided to the study site. Randomization details will be 
included in the randomization specification. 


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5.4. 
Blinding 
This is a double-blinded study. The following controls will be employed to maintain the 
double-blind status of the study: 
• The placebo will be identical in appearance to CBP-307 or moxifloxacin. 
• The investigator and other members of staff involved with the study will remain 
blinded to the treatment randomization code during the assembly procedure. 
• Interim bioanalytical data will be provided to Labcorp Early Clinical Biometrics in a 
blinded manner. 
To maintain the blind, the investigator will be provided with a sealed randomization code for 
each subject, containing coded details of the treatment. These individually sealed envelopes 
will be kept in a limited access area that is accessible 24 hours a day. If, in order to manage 
subject safety or to support dose escalation decisions (in the event of possibly 
treatment-related SAEs or severe AEs), the decision to unblind resides solely with the 
investigator. Whenever possible, and providing it does not interfere with or delay any 
decision in the best interest of the subject, the investigator will discuss the intended 
code-break with the sponsor. If it becomes necessary to break the code during the study, the 
date, time, and reason will be recorded in the subject's source data and on the individual 
envelope and will be witnessed by a second person. 
5.5. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of suitably qualified study site 
staff. 
• Immediately after dose administration, visual inspection of the mouth and hands will 
be performed for each subject. 
• At each dosing occasion, a predose and postdose inventory of IMP will be performed.   
5.6. 
Drug Accountability 
The investigator (or designee) will maintain an accurate record of the receipt of study 
treatments (CBP-307, moxifloxacin, placebo-matched CBP-307, and placebo-matched 
moxifloxacin) received. In addition, an accurate drug disposition record will be kept, 
specifying the amount dispensed to each subject and the date of dispensing. This drug 
accountability record will be available for inspection at any time. At the completion of the 
study, the original drug accountability record will be available for review by the sponsor 
upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused 
assembled unit doses will be retained until the completion of the study. 


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At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the 
study site’s pharmacy, per the sponsor’s written instructions. If destruction is authorized to 
take place at the study site’s pharmacy, the investigator must ensure that the materials are 
destroyed in compliance with applicable environmental regulations and institutional policy. 
All study drug destructions must be adequately documented. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects will refrain from the use of any prescription or nonprescription medications/products 
during the study until the follow-up visit, unless the investigator (or designee) and/or sponsor 
have given their prior consent. Medications taken within 28 days before study treatment 
administration will be documented as a prior treatment. Treatments taken after study 
treatment administration will be documented as concomitant treatments. 
Paracetamol/acetaminophen (2 g/day for up to 3 consecutive days) is an acceptable 
concomitant medication. The administration of any other concomitant medications during the 
study is prohibited without prior approval of the investigator (or designee), unless its use is 
deemed necessary for the treatment of an AE. Any medication taken by a subject during the 
course of the study and the reason for its use will be documented in the source data.  
Females will refrain from the use of hormone replacement therapy and oral, implantable, 
transdermal, injectable, or intrauterine hormonal contraceptives (with the exception of 
Mirena®) during the study until the follow-up visit (Appendix 4). 
6.2. 
Diet 
While confined at the study site, subjects will receive a standardized diet at scheduled times 
that do not conflict with other study-related activities. Subjects will be fasted overnight (at 
least 10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be 
allowed from 7 days prior to check-in until follow-up visit on Day 29±2 days. 
Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 19. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge 
on Day 19 and alcohol intake will be limited to a maximum of 2 units/day on all other days, 
whilst not at the study site, from screening to 72 hours prior to the follow-up visit on 
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6.3. 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 
3 months prior to check-in until the follow-up visit. 
6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 29±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 3 months prior to screening, 
plasma from 2 weeks prior to screening, and platelets from 6 weeks prior to screening until 
3 months after the follow-up visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. The order of 
priority for scheduling procedures around a timepoint is (in descending order of priority): 
• dosing 
• continuous ECG extraction window 
• pharmacokinetic blood samples 
• safety assessments  
• any other procedures. 
This study includes a screening period (Day -28 to Day -3), a treatment period (Days -2 to 
19), and a follow-up period (Day 29 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2) 
or baseline (Day -1 predose) will only be considered exclusionary if judged applicable by the 
investigator. For confirmation of enrollment eligibility based on pulse rate, the pulse rate 
assessed by vital signs, rather than the 12-lead ECG, will be used. For all subjects, the 
screening, check-in, or baseline blood pressure, pulse rate, and respiratory rate may be 
repeated after 5 to 10 minutes if the initial reading is believed to be atypical for the subject. 


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7.1. 
General Assessments 
7.1.1. 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in order 
to study their possible association with subject safety and treatment effectiveness. 
7.1.2. 
Medical History 
At the timepoint specified in Appendix 6, the investigator or designee will collect a complete 
medical and surgical history. Medical history will include information on the subject’s 
concurrent medical conditions and any events occurring prior to the first dose of study 
treatment. All findings will be recorded on the medical history eCRF. 
7.2. 
Electrocardiography Assessments 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording 
Continuous 12-lead digital ECG recording will be performed as specified in Appendix 6. All 
ECG data will be collected using a Holter (or Mortara Surveyor) ECG continuous 12-lead 
digital recorder. The 12-lead Holter (or Mortara Surveyor) ECG equipment will be supplied 
and supported by ERT (eResearch Technology Inc., Philadelphia, PA). The continuous 
12-lead digital ECG data will be stored onto SD memory cards.  
The ECGs to be used in the analyses will be selected by predetermined timepoints as defined 
in Appendix 6 and will be read centrally by ERT (eResearch Technology Inc., Philadelphia, 
PA). The following principles will be followed in ERT’s core laboratory: 
• ECG analysts are blinded to the subject, visit, and treatment allocation. 
• Baseline and on-treatment ECGs for a particular subject will be over-read on the same 
lead and will be analyzed by the same reader. 
The primary analysis lead is lead II. If lead II is not analyzable, then the primary lead of 
analysis will be changed to another lead for the entire subject data set. 
The 12-lead ECGs will be extracted in up to 10 replicates at the predefined timepoints and 
subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 minutes 
after each nominal time. 
7.2.1.1. 
TQT Plus Extraction Technique 
Ten 14-second digital 12-lead ECG tracings will be extracted from the continuous Holter (or 
Mortara Surveyor) recordings using the ‘TQT Plus method’, a computer-assisted and 
statistical process utilized by ERT. The method enables extraction of ECGs with the lowest 
HR variability and noise within the protocol-specified extraction time window (eg, the HR 
and QT changes from beat-to-beat in the range of <10%). At each protocol-specified 
timepoint, 10 ECG replicates will be extracted from a 5-minute “ECG window” (typically, 


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the last 5 minutes of the 15-minute period when the subject is maintained in a supine, quiet 
position). 
7.2.1.2. 
Expert Precision QT Analysis 
Expert precision QT analysis will be performed on all analyzable (non-artifact) beats in the 
10 ECG replicates. Statistical quality control procedures are used to review and assess all 
beats and identify “high” and “low” confidence beats using several criteria, including: 
• QT or QTc values exceeding or below certain thresholds (biologically unlikely). 
• RR values exceeding or below certain thresholds (biologically unlikely). 
• Rapid changes in QT, QTc, or RR from beat-to-beat. 
Measurements of all primary ECG parameters (QT, QTc, RR) in all recorded beats of all 
replicates that are deemed “high confidence” will be performed using COMPAS software. 
All low-confidence beats will be reviewed manually and adjudicated using pass-fail criteria. 
The final QC assessment will be performed by a cardiologist. The beats found acceptable by 
manual review will be included in the analysis. The median QT, QTc, and RR values from 
each extracted replicate will be calculated, and then the mean of all available medians from a 
nominal timepoint will be used as the subject’s reportable value at that timepoint. 
Categorical T-wave morphology analysis and the measurement of PR and QRS interval of the 
ECG (QRS) intervals will be performed manually in 3 of the 10 ECG replicates at each 
timepoint. Each fiducial point (onset of P-wave, onset of Q-wave, offset of S-wave, and 
offset of T-wave) will be electronically marked. 
For T-wave morphology and U-wave presence, treatment-emergent changes will be assessed 
(ie, changes not present at baseline). For each category of T-wave morphology and U-waves, 
the category will be deemed as present if observed in any replicate at the timepoint. For 
baseline, the category will be deemed as present if observed in any replicate from all 
timepoints that constitute baseline. 
7.2.2. 
Safety 12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at 
least 5 minutes at the times indicated in the Schedule of Assessments in Appendix 6. Single 
12-lead ECGs will be repeated twice, and an average taken of the 3 readings, if either of the 
following criteria applies: 
• QT interval corrected for HR using Fridericia’s method (QTcF) is >500 ms 
• QTcF change from the baseline (predose) is >60 ms. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically 
appropriate or if the ongoing review of the data suggests a more detailed assessment of ECGs 
is required. The investigator (or designee) will perform a clinical assessment of each 12-lead 
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7.2.3. 
Cardiac Telemetry Monitoring 
Subjects will be monitored via cardiac telemetry from approximately 1 hour prior to dose 
administration and until approximately 12 hours postdose on Days 1, 2, 3, and 7 (up-titration 
days; as described in Appendix 6). Based on the emerging safety data from the study, the 
duration of the telemetry may be extended if necessary. 
The start and stop date and time of the telemetry monitoring will be recorded in the eCRFs. 
Clinically significant abnormalities noted from telemetry monitoring will be confirmed by 
12-lead ECG if necessary, then after confirming, the abnormities will be reported as AEs in 
the eCRF. 
7.3. 
Pharmacokinetic Assessments  
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples (approximately 1 × 4 mL for CBP-307 and moxifloxacin assays) will be 
collected by venipuncture or cannulation at the times indicated in the Schedule of 
Assessments in Appendix 6. Procedures for collection, processing, and shipping of PK blood 
samples will be detailed in a separate document.  
7.3.2. 
Analytical Methodology 
Plasma concentrations of CBP-307 and moxifloxacin will be determined using a validated 
analytical procedure. Specifics of the analytical method will be provided in a separate 
document.  
7.4. 
Safety and Tolerability Assessments 
7.4.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF until the 
follow-up visit. Subjects will be observed for any signs or symptoms and asked about their 
condition by open questioning, such as “How have you been feeling since you were last 
asked?”, at least once each day while resident at the study site and each study visit. Subjects 
will also be encouraged to spontaneously report AEs occurring at any other time during the 
study. 
All nonserious AEs, whether reported by the subject voluntarily or upon questioning, or 
noted on physical examination, will be recorded from initiation of placebo administration to 
all subjects (Day -1) until study completion. If AEs that occur in the screening prior to 
placebo administration to all subjects (Day -1) are considered to be related to the study 
procedure, they should be also collected. Serious AEs will be recorded from the time the 
subject signs the ICF until study completion. The nature, time of onset, duration, and severity 
will be documented, together with an investigator’s (or designee’s) opinion of the 
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Adverse events recorded during the course of the study will be followed up, where possible, 
to resolution or until the unresolved AEs are judged by the investigator (or designee) to have 
stabilized. This will be completed at the investigator’s (or designee’s) discretion. 
7.4.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations at the times 
indicated in the Schedule of Assessments in Appendix 6. Clinical laboratory evaluations are 
listed in Appendix 2. 
A serum qualitative pregnancy or urine test (females only) and follicle-stimulating hormone 
test (postmenopausal females only) will be performed at the timepoints specified in 
Appendix 6. A positive urine pregnancy test will be confirmed with a serum pregnancy test. 
All pregnancies should be reported as specified in Appendix 1. 
Additional clinical laboratory evaluations will be performed at other times if judged to be 
clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of clinical laboratory safety evaluations is required. At the discretion of the 
investigator, clinically significant clinical laboratory assessments may be confirmed by repeat 
sampling. If the clinical significance is confirmed, subjects will be excluded from 
participation or, if already included, will be followed until normalization of the test result or 
for as long as the investigator considers necessary. 
Subjects will be asked to provide urine samples for drugs of abuse screen and cotinine test, 
and will undergo an alcohol breath test at the times indicated in the Schedule of Assessments 
in Appendix 6. For all female subjects, a pregnancy test will be performed at the times 
indicated in the Schedule of Assessments in Appendix 6.   
An investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.4.3. 
Vital Signs 
Supine blood pressure, supine pulse rate, respiratory rate, and tympanic temperature will be 
assessed at the times indicated in the Schedule of Assessments in Appendix 6. Vital signs 
may also be performed at other times if judged to be clinically appropriate or if the ongoing 
review of the data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly. For all subjects, the screening, check-in, or 
baseline blood pressure, pulse rate, and respiratory rate may be repeated after 5 to 10 minutes 
if the initial reading is believed to be atypical for the subject. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
7.4.4. 
Physical Examination 
A full physical examination will be performed at the timepoints specified in the Schedule of 
Assessments in Appendix 6. Physical examinations include general appearance, head, eyes, 


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ears, nose, and throat, neck (including thyroid and nodes), cardiovascular, respiratory, 
gastrointestinal, renal, neurological, musculoskeletal, skin, and others. 
Height, weight, and body mass index will be assessed at screening. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Sample Size for Primary Analysis: 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-msec QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-307 
in the study. This power is estimated approximately using a 2-sample t-test. The calculation 
assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 3 msec and a 
standard deviation (SD) of the ΔQTcF of 8 msec for both CBP-307 and placebo treatment 
groups. Note that this calculation is conservative, since it does not take into account any gain 
in precision due to the use of all data of each subject with the help of a linear mixed-effects 
model. The concentration-QTc analysis method is supported by Darpo et al 20153 and 
Ferber et al, 2015,4 and consistent with the experiences from 25 recent TQT studies. 
Sample Size Considerations for Assay Sensitivity: 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that the 
ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 msec (ie, the lower bound of the 
2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 msec). In a similarly 
designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the standard 
error (SE) for the prediction of the QT effect of moxifloxacin based on the exposure-response 
analysis was 1.24 msec. The within-subject SD of ΔQTcF in the referred study was 5.4 msec 
based on the by-timepoint analysis. If the effect of moxifloxacin is assumed to be 10 msec, 
the SE of 1.24 msec corresponds to an effect size of (10-5)/(1.24×sqrt[24])=0.82, where the 
effect size is the effect assumed under the alternative hypothesis divided by the SD of the test 
variable. This value should be compared to the effect size of 0.64 required to guarantee a 
power of at least 95% in a paired t-test situation with a sample size of 28 evaluable subjects. 
In other words, based on this calculation, a power of at least 95% will be obtained as long as 
the variability of the ΔQTcF, as measured by its within-subject SD from the by-timepoint 
analysis, does not exceed 6.9 msec (ie, 128% [= 0.82/0.64] of the 5.4 msec observed in the 
referred study assuming the ratio of effective sizes is consistent with inverse ratio of 
within-subject SD). The number also agrees with recent recommendations of the FDA, which 
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8.2. 
Analysis Populations 
8.2.1. 
Cardiodynamic Population 
The QT/QTc population will include all subjects in the safety population with measurements 
at baseline as well as on-treatment with at least 1 postdose timepoint with a valid ΔQTcF 
value. The QT/QTc population will be used for the by-timepoint and categorical analyses of 
the cardiodynamic ECG parameters. 
The PK/QTc population will include all subjects who are in both the QT/QTc and PK 
populations with at least 1 pair of postdose PK and ∆QTcF data from the same timepoint as 
well as subjects in the QT/QTc population who received placebo. The PK/QTc population 
will be used for the concentration-QTc analysis and assay sensitivity. PK/QTc population 
will be defined for CBP-307, and for moxifloxacin.  
The as-treated principle will be applied to all analysis populations mentioned below. 
8.2.2. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of investigational 
product and have evaluable PK data of any of the analytes (CBP-307 and moxifloxacin). A 
subject will be excluded from the PK summary statistics and statistical analysis if the subject 
has an AE of vomiting that occurs at or before 2 times median time to maximum 
concentration.  
8.2.3. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of investigational 
product drug (therapeutic and supratherapeutic doses of CBP-307, moxifloxacin, or placebo). 
8.3. 
Cardiodynamic ECG Analyses 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus 
placebo in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1 (defined as Period 1 Day 1), 
baseline will be Day 16 (defined as Period 1 Day -1), on which subjects are 
administered placebo. For placebo-correction in this group, placebo values will be 
derived from Day 15 (defined as Period 2 Day 1) on which subjects are administered 
placebo, and baseline will be obtained on Day -1 (defined as Period 2 Day -1). 
• Group 2B: For moxifloxacin administered on Day 16 (defined as Period 2 Day 1), 
baseline will be Day 1 (defined as Period 2 Day -1), on which subjects are 
administered placebo. For the placebo-correction in this group, Day -1 (defined as 


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Period 1 Day 1) values will be used as placebo (no treatment) and baseline will be 
obtained on Day 15 (defined as Period 1 Day -1). 
Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as 
the dependent variable, time-matched concentrations of CBP-307 as the exploratory variate 
(0 for placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on 
Days 1, 6, and 15 categorical) as fixed effects, and a random intercept and slope per subject.6 
Centered baseline QTcF (i.e., baseline QTcF for individual subject minus the population 
mean baseline QTcF for all subjects) will be included in this model as an additional covariate. 
If necessary, a sensitivity analysis will be performed using the model without this term. 
The degrees of freedom estimates will be determined by the Kenward-Roger method. From 
the model, the slope (ie, the regression parameter for the CBP-307 concentration) and the 
treatment effect-specific intercept will be estimated together with 2-sided 90% CI. The 
estimates for the time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-timepoint analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 6, 
and 15, and Days 1 and 16 for active versus placebo and moxifloxacin versus placebo, 
respectively. All times are relative to the time of dosing on that day which is considered the 
first dose for the assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the 
first dose of study treatment is on Day 1. 
The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in 
the active drug groups on each of Days 6 and 15 will be determined, respectively. The 
predicted effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF 
(ΔΔQTcF) (ie, slope estimate × concentration + treatment effect-specific intercept) at this 
geometric mean Cmax will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the 
observed ΔQTcF values adjusted by population time effect estimated from the model will be 
used. These individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed 
individual ΔQTcFi,k for subject i administered with active drug or placebo at timepoint k 
minus the estimated population mean placebo effect at timepoint k (ie, time effect). A decile 
plot, ie, plot of the deciles of observed concentrations and the mean placebo-adjusted ΔQTcF 
(ΔΔQTcF) and 90% CI at the median concentration within each decile will be given. The 
regression line presenting the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a 
linear model and visualize the concentration-response relationship. The placebo-adjusted 
ΔQTcFi,j equals the individual ΔQTcFi,j for subject i administered with CBP-307 at timepoint 
j minus the estimation of time at timepoint j (ie, time effect). Additional exploratory analyses 
(via graphical displays and/or model fitting) will include accounting for a delayed effect 
(hysteresis) and the justification for the choice of PD model (linear versus nonlinear) as 
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Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the 
observed geometric mean Cmax on Days 6 and 15 as well as clinically relevant plasma levels 
is below 10 msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax 
<10 msec), it can be concluded that CBP-307 does not cause clinically concerning QT 
prolongation within the observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 6 and 15; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on 
Days 6 and 15; and if the difference (delay) between the time to reach the peak QTc effect 
(ΔΔQTcF) and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of 
more than 1 hour is observed in a consistent way for the active dose groups on Days 6 and 15, 
other concentration-QTc models, such as a model with an effect compartment, may be 
explored. With the provision stated above, hysteresis will be assumed if this curve shows a 
counterclockwise loop. A significant treatment effect-specific intercept may also be 
indicative of hysteresis or model misspecification, if it cannot be explained by a nonlinear 
relationship. 
Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 
time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a 
scatter plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI 
and a linear regression line will also be provided to check the assumption of a linear 
concentration-QTc relationship. If there is an indication that a linear model is inappropriate, 
additional models may be fitted, such as an E-max model. The concentration-QTc analysis 
will then be repeated for the model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of 
moxifloxacin data. If the slope of the concentration-QTc (change-from-baseline QTcF) for 
moxifloxacin is statistically significant at 10% level for 2-sided test and the lower bound of 
the 2-sided 90% CI of the predicted effect is above 5 msec at the observed geometric mean 
Cmax of the 400-mg dose, assay sensitivity will be deemed to have been demonstrated. 


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By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 
time-by-treatment interaction as fixed effects. Baseline QTcF will be included in this model 
as an additional covariate. If necessary, a sensitivity analysis will be performed using the 
model without this term. An unstructured covariance matrix will be specified for the repeated 
measures at postdose timepoints within subjects. If the model with unstructured covariance 
matrix fails to converge, other covariance matrices such as compound symmetry and 
autoregressive will be considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs 
will be calculated for the contrast “CBP-307 versus placebo” for each day of Days 1, 6, and 
15 at each postbaseline timepoint on Days 1, 6, and Day 15, respectively. 
The by-timepoint analysis for QTcF will be also performed for moxifloxacin versus placebo 
at postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used 
with ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 
16: categorical), treatment (moxifloxacin and placebo), period (as described in baseline 
definition for assay sensitivity), sequence (placebo/moxifloxacin or moxifloxacin/placebo), 
and time-by-treatment interaction as fixed effects. Baseline QTcF will be included in this 
model as an additional covariate. If necessary, a sensitivity analysis will be performed using 
the model without this term. An unstructured covariance matrix will be specified for the 
repeated measures at postbaseline timepoints for subject within visit. The model will also 
include a subject-specific random effect. If the model with an unstructured covariance matrix 
fails to converge, other covariance matrices, such as compound symmetry or autoregressive, 
will be considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs will be 
calculated for the contrast “moxifloxacin versus placebo” at each postbaseline timepoint on 
Day 1, respectively. 
For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline 
postdose (ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as 
described for QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both 
change-from-baseline and placebo-corrected change-from-baseline values will be listed in the 
tables and graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will 
be summarized in frequency tables with counts (percentages) for both the number of subjects 
and the number of timepoints. For categorical outliers, the number (percentage) of subjects as 
well as timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 
and ≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline 
>25% to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR 
>100 bpm will be determined. For T-wave morphology and U-wave presence, the analyses 
will be focused on change from baseline (ie, treatment-emergent changes). 


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8.4. 
Pharmacokinetic Analyses 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, SD, median, minimum, 
maximum geometric mean, and geometric coefficient of variation) separately by group. 
Individual and mean plasma CBP-307 and moxifloxacin concentration versus time data will 
be tabulated and plotted by dose level. Graphical displays of PK data may be provided as 
well.  
For each subject, the following PK parameters will be calculated, whenever possible, based 
on the plasma concentration for CBP-307 and moxifloxacin, according to the model 
independent approach: 
• Cmax 
• tmax 
• AUC0-24  
• AUCinf 
• apparent terminal elimination rate constant (λZ) 
• t1/2  
• apparent total clearance (CL/F) 
• apparent volume of distribution during the terminal phase (Vz/F)  
Pharmacokinetic calculations will be performed, if appropriate, using commercial software 
such as Phoenix® WinNonlin® (Version 8.1 or higher). 
Other parameters may be added as appropriate. 
Pharmacokinetic analysis will use actual times as recorded on the eCRF. Other data handling 
procedures will be detailed in the Statistical Analysis Plan. 
8.5. 
Safety Analysis 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed.   
8.6. 
Interim Analysis 
No interim analyses are planned for this study.  


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9. REFERENCES 
1. Suzhou Connect. CBP-307 – Investigator’s Brochure. (Version 6.0). December 2020. 
2. Avelox [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016. 
3. Darpo B, Benson C, Dota C, et al. Results from the IQ-CSRC prospective study support 
replacement of the thorough QT study by QT assessment in the early clinical phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
4. Ferber G, M Zhou, B Darpo. Detection of QTc effects in small studies--implications for 
replacing the thorough QT study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
5. Huang DP, Chen J, Dang Q, et al. Assay sensitivity in “Hybrid thorough QT/QTc (TQT)” 
study. Journal of Biopharmaceutical Statistics. 2019;29(2):378-384. 
6. Garnett C, Bonate PL, Dang Q , et al. Scientific white paper on concentration-QTc 
modeling. [Published correction appears in J Pharmacokinet Pharmacodyn. 
2018;45(3):399]. J Pharmacokinet Pharmacodyn. 2018;45(3):383-397. 
7. Tornøe CW, Garnett CE, Wang Y, et al. Creation of a knowledge management system for 
QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042. 
8. Cleveland WS. Robust Locally Weighted Regression and Smoothing Scatter Plots. 
J Amer Statist Assoc. 1979;74(368):829-36. 
9. Hurvich CM, Simonoff JS, Tsai CL. Smoothing parameter selection in nonparametric 
regression using an improved Akaike information criterion. J Roy Statist Soc Ser B Stat 
Methodol. 1998;60(2):27-193. 
 
 


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10. APPENDICES 


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Appendix 1: Adverse Event Reporting 
Definitions 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a study treatment, whether or not related to the study 
treatment. This includes any newly occurring event or previous condition that had increased 
in severity or frequency since the administration of study medication.  
Examples of AEs include: 
•
Symptoms described by the subject, or signs observed by the investigator, and
•
Abnormal findings (involving clinically significant abnormal laboratory tests, ECG,
etc.)
•
Exacerbation of previous condition, including increased incidence and/or severity.
Note: Regarding decreased lymphocyte count in peripheral blood in this study, please report 
them as follows: 
•
Since a decreased lymphocyte count in peripheral blood is due to the mechanism of
action of the drug, it is not to be reported as an AE. However, clinical diagnosis
related to a decreased lymphocyte count in peripheral blood indicates AE reporting (if
no diagnosis is available, it is required to report related clinical symptoms or signs).
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs. All AEs will 
be recorded in the medical records and eCRFs. The investigator (or designee) is to record in 
detail any AE that occurred to the subject, including: AE diagnosis whenever possible, or 
signs, symptoms, the start date and time of occurrence, the stop date and time of occurrence, 
seriousness (ie, whether it is an SAE), severity of AEs, causality assessment, actions taken on 
the investigational product, other actions (eg, medications/treatments given), and outcomes of 
AEs.  
Assessment of Severity 
The investigator will be asked to provide an assessment of the severity of the AE using the 
following categories:  
•
Mild: Usually transient and may require only minimal treatment or therapeutic
intervention. The event does not generally interfere with usual activities of daily
living.
•
Moderate: Usually alleviated with additional specific therapeutic intervention. The
event interferes with usual activities of daily living, causing discomfort but poses no
significant or permanent risk of harm to the subject.


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•
Severe: Interrupts usual activities of daily living, or significantly affects clinical
status, or may require intensive therapeutic intervention.
Relationship to Study Treatment 
The investigator (or designee) will make a determination of the relationship of the AE to the 
study treatment using a 4-category system according to the following guidelines: 
•
Not Related: The AE is definitely caused by the subject’s clinical state or the study
procedure/conditions.
•
Unlikely Related: The temporal association between the AE and the drug is such that
the drug is not likely to have any reasonable association with the AE.
•
Possibly Related: The AE follows a reasonable temporal sequence from the time of
drug administration but could have been produced by the subject’s clinical state or the
study procedures/conditions.
•
Related: The AE follows a reasonable temporal sequence from the administration of
the drug, abates upon discontinuation of the drug, follows a known or hypothesized
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced.
Follow-up of Adverse Events 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject 
who has an ongoing AE that is possibly related or related to the IMP or study procedures at 
the follow-up visit will be followed up, where possible, until resolution or until the 
unresolved AE is judged by the investigator (or designee) to have stabilized. This will be 
completed at the investigator’s (or designee’s) discretion. Any subject who has an ongoing 
AE that is not related or unlikely related to the IMP or study procedures at the follow-up visit 
can be closed out as ongoing at the investigator’s discretion.  
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
For marketed medicinal products, a response to a drug that is noxious and unintended and 
which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases 
or modification of physiological function is to be considered an adverse drug reaction. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, IB for an unapproved 
IMP). 
Serious Adverse Events 
All SAEs will be collected after subjects sign the informed consent form and throughout the 
entire study, ie, until the end-of-study as specified in the protocol (or at early termination). 


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An SAE is defined as any untoward medical occurrence that at any dose either: 
•
results in death
•
is life-threatening
•
requires inpatient hospitalization or prolongation of existing hospitalization
•
results in persistent or significant disability/incapacity (disability is defined as a
substantial disruption of a person’s ability to conduct normal life functions)
•
results in a congenital anomaly/birth defect
•
results in an important medical event (see below).
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Instances of death or congenital abnormality, if brought to the attention of the investigator at 
any time after cessation of the study treatment and considered by the investigator to be 
possibly related to the study treatment, will be reported to the sponsor (or designee). 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalization 
Adverse events requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the subject has been detained (usually involving an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate at the study site. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered as serious. 
Hospitalization for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a clinical assessment form and 
added to the eCRF. If anything untoward is reported during the procedure, this must be 
reported as an AE and either ‘serious’ or ‘nonserious’ attributed according to the usual 
criteria. 
Serious Adverse Event Reporting 
The investigator will complete an SAE report form and forward it by facsimile or email to 
Labcorp Drug Safety and the sponsor immediately (within 24 hours) upon becoming aware of 
an SAE. 


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All SAEs must be reported immediately (within 24 hours of discovery) to: 
+61-2-8879-2000 (AUS) or 1-888-887-8097 (US)
SAE Reporting email: SAEIntake@labcorp.com (preferred method) 
Labcorp Safety SAE Reporting Fax Numbers: 61-2-6100-9788 or 1800-882-203 (toll free) in 
Australia and 1-888-887-8097 (toll free) in the US 
The responsibilities of Labcorp Drug Safety include the following: 
•
Prepare an AE reporting plan prior to the start of the study. Where this plan differs
from the applicable study site standard operating procedure on SAE reporting, the
safety management plan will always take precedence.
•
Receive and review SAE report forms from the study site and inform the sponsor of
the SAE within 1 working day of the initial notification to Labcorp Drug Safety who
will delete any information from the SAE report forms that may identify the subject.
•
Write case narratives and enter the case into Labcorp’s safety database as defined in
the AE reporting plan.
•
Produce appropriate reports of all suspected unexpected serious adverse reactions and
forward them to the IRB/EC, Medicines and Healthcare Products Regulatory Agency,
FDA, principal investigator, and the sponsor within the timeframes stipulated in the
Clinical Trials Directive Guideline (ENTR/CT 3).
The responsibility for reporting SAEs will be transferred to the sponsor 28 days after the end 
of the study. 
For SAEs, the active reporting period to sponsor or its designated representative begins from 
the time that the subject provides informed consent through to the last subject visit.  
Nonserious AEs should be collected from the time the subject has taken the placebo dose on 
Day -1 through the last subject visit. If AEs that occur in the screening prior to the placebo 
administration to all subjects on Day -1 are considered to be related to the study procedure, 
they should be also collected.  
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, the 
sponsor should be notified within 24 hours of investigator awareness of the event. This time 
frame also applies to additional new information (follow-up) on previously forwarded SAE 
reports as well as to the initial and follow-up reporting of exposure during pregnancy.  
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.  
For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the time frames for reporting as specified above. In addition, an investigator 


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may be requested by the sponsor to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured on 
the AE eCRF. In general, this will include a description of the AE in sufficient detail to allow 
for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to the sponsor 
or its designated representative. 
Pregnancy 
Pregnancy (maternal or paternal exposure to study treatment) does not meet the definition of 
an AE. However, to fulfill regulatory requirements any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus. 
If the female subject becomes pregnant during the clinical trial and has not yet been dosed 
with study treatment, she must be withdrawn from the study. If the female subject becomes 
pregnant during the clinical trial and has been dosed, she must discontinue treatment 
immediately but may remain on study for safety evaluations. If the partner of a male subject 
becomes pregnant during the clinical trial, the subject can continue the clinical trial.  
For pregnancy of female subjects or partners of the male subjects during this study, 
investigators should report to the sponsor or designee in a pregnancy report form within 
24 hours after investigator awareness and report to the IRB/EC in time as per local 
requirement.  
The investigator will follow up on pregnancy outcomes, until not less than 12 months after 
birth, unless otherwise justified, and will report the outcome to the sponsor and IRB/EC.  
If any adverse pregnancy outcome (eg, the outcome of the pregnancy is stillbirth, 
spontaneous abortion, or fetal malformations), it should be considered as an SAE and be 
reported in accordance with SAE reporting requirements. 


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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate  
Magnesium 
Potassium  
Sodium  
Total bilirubin
Total protein 
Urea 
Uric acid 
Hematocrit  
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell count 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
Blood 
Glucose 
Ketones 
Leukocyte esterase  
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination  (if 
indicated by dipstick) 
Serology: 
Drug screen: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency (HIV-1 
and HIV-2) antibodies and p24 
antigen 
Syphilis 
Including but not limited to:  
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol 
Tricyclic antidepressants 
Cotinine test 
Follicle-stimulating hormone 
(postmenopausal females only) 
Serum pregnancy test (human 
chorionic gonadotropin)b 
Urine pregnancy testb  
Other Tests 
Low density lipoprotein cholesterol 
High-density lipoprotein 
cholesterol 
Triglycerides 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated.  
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the 
follow-up visit (on Day 29±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  


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Appendix 3: Total Blood Volume 
The following blood volumes will be withdrawn for each subject. 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
41 
328 
Total: 
390.5 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed 500 mL. 


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Appendix 4: Contraception Guidance 
Definitions 
Women of Childbearing Potential: premenopausal females who are anatomically and 
physiologically capable of becoming pregnant following menarche. 
Women of Nonchildbearing Potential: 
1. Surgically sterile: females who are permanently sterile via hysterectomy,
bilateral salpingectomy, and/or bilateral oophorectomy by reported medical
history and/or medical records. Surgical sterilization to have occurred a minimum
of 6 weeks, or at the investigator’s discretion, prior to screening.
2. Postmenopausal: females at least 45 years of age with amenorrhea for 12 months
without an alternative medical reason with confirmatory follicle-stimulating
hormone (FSH) levels of ≥40 mIU/mL. The amenorrhea should not be induced by
a medical condition such as anorexia nervosa, hypothyroid disease or polycystic
ovarian disease, or by extreme exercise. It should not be due to concomitant
medications that may have induced the amenorrhea such as oral contraceptives,
hormones, gonadotropin-releasing hormones, anti-estrogens, or selective estrogen
receptor modulators. Females on hormone replacement therapy with FSH levels
<40 mIU/mL may be included at the discretion of the investigator.
Fertile male: a male that is considered fertile after puberty. 
Infertile male: permanently sterile male via bilateral orchiectomy. 
Contraception Guidance 
Female Subjects 
Female subjects who are of nonchildbearing potential will not be required to use 
contraception. Female subjects of childbearing potential must be willing to use 2 methods 
(1 primary and 1 secondary method) of birth control from the time of signing the ICF until 
90 days after the follow-up visit. Primary (non-barrier) methods of contraception include: 
•
surgical method performed at least 3 months prior to the screening visit:
o
bilateral tubal ligation or bilateral salpingectomy
o
Essure® (hysteroscopic bilateral tubal occlusion) with confirmation of
occlusion of the fallopian tubes
•
non-hormonal intrauterine device or Mirena® (other hormonal intrauterine devices
will not be allowed) in place for at least 3 months prior to the first dose of the study
drug
•
vasectomized male partner (sterilization performed at least 90 days prior to the
screening visit, with verbal confirmation of surgical success, and the sole partner for
the female subject)


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Secondary (barrier) methods of contraception include: 
•
male condom without spermicide
•
female condom without spermicide
•
cervical cap without spermicide (as prescribed)
•
diaphragm without spermicide (as prescribed).
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2) until 90 days after the follow-up visit. 
Male Subjects 
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (ie, male condom without spermicide) in addition 
to a second method of acceptable contraception from check-in until 90 days after the 
follow-up visit. Acceptable methods of contraception for female partners include: 
•
hormonal injection
•
combined oral contraceptive pill or progestin/progestogen-only pill
•
combined hormonal patch
•
combined hormonal vaginal ring
•
surgical method (bilateral tubal ligation or Essure® [hysteroscopic bilateral tubal
occlusion])
•
hormonal implant
•
hormonal or non-hormonal intrauterine device
•
cervical cap without spermicide
•
diaphragm without spermicide.
An acceptable second method of contraception for male subjects is vasectomy that has been 
performed at least 90 days prior to the screening visit with verbal confirmation of surgical 
success. 
For male subjects (even with a history of vasectomy), sexual intercourse with female partners 
who are pregnant or breastfeeding should be avoided unless condoms are used from the time 
of the first dose until 90 days after the follow-up visit. Male subjects are required to refrain 
from donation of sperm from check-in until 90 days after the follow-up visit. 
Sexual Abstinence and Same-sex Relationships 
Subjects who practice true abstinence, because of the subject’s lifestyle choice (ie, the subject 
should not become abstinent just for the purpose of study participation), are exempt from 
contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, symptothermal, 
postovulation methods) and withdrawal are not acceptable methods of contraception. If a 


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subject who is abstinent at the time of signing the ICF becomes sexually active they must 
agree to use contraception as described previously.  
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. If a subject who is in a same-sex relationship at the time of signing the ICF becomes 
engaged in a heterosexual relationship, they must agree to use contraception as described 
previously. 


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Appendix 5: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol, local legal and regulatory 
requirements and with the following: 
•
General principles set forth in the International Ethical Guidelines for Biomedical
Research Involving Human Subjects (Council for International Organizations of
Medical Sciences 2002), Guidelines for good clinical practice (GCP) (ICH 1996), and
the Declaration of Helsinki (World Medical Association 2008).
•
Applicable laws and regulations.
The protocol, protocol amendments, ICF, IB, and other relevant documents must be 
submitted to the institutional review board (IRB)/human research ethics committee (HREC) 
by the investigator and reviewed and approved by the IRB/HREC before the study is 
initiated.  
Any protocol amendments will require IRB/EC approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study subjects.  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents from the 
IRB/HREC. All correspondence with HREC should be retained in the investigator file. A 
copy of /IRB/HREC approval should be forwarded to the sponsor. 
The investigator will be responsible for the following: 
•
Providing written summaries of the status of the study to the IRB/EC annually or
more frequently in accordance with the requirements, policies, and procedures
established by the IRB/EC.
•
Notifying the IRB/EC of SAEs or other significant safety findings as required by
IRB/EC procedures.
•
Providing oversight of the conduct of the study at the site and adherence to
requirements of ICH guidelines, the IRB/EC, and all other applicable local
regulations.
Regulatory Authority 
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency 
in accordance with any applicable country-specific regulatory requirements before the study 
is initiated at a study center in that country. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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Informed Consent 
Prior to starting participation in the study, each subject will be provided with a study-specific 
ICF giving details of the study treatments, procedures, and potential risks of the study. 
Subjects will be instructed that they are free to obtain further information from the 
investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. Subjects will be given an opportunity to ask questions 
about the study prior to providing consent for participation. 
Following the discussion of the study with study site personnel, subjects will sign the ICF in 
the presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. A copy of the ICF will be given to the subject. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
Subject Data Protection 
Subjects will be assigned a unique identifier and will not be identified by name in eCRFs, 
study-related forms, study reports, or any related publications. Subject and investigator 
personal data will be treated in compliance with all applicable laws and regulations. In the 
event the study protocol, study report, or study data are included in a public registry, all 
identifiable information from individual subjects or investigators will be redacted according 
to applicable laws and regulations.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. The subject must also be informed that his/her study-related data 
may be examined by sponsor or contract research organization (CRO) auditors or other 
authorized personnel appointed by the sponsor, by appropriate IRB/EC members, and by 
inspectors from regulatory authorities. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the sponsor. 
Data Quality Assurance 
The following data quality steps will be implemented: 
•
All relevant subject data relating to the study will be recorded on eCRFs unless
directly transmitted to the sponsor or designee electronically (eg, laboratory data). The
investigator is responsible for verifying that data entries are accurate and correct by
electronically signing the eCRF.


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 62 of 67 
•
The investigator must maintain accurate documentation (source data) that supports the
information entered in the eCRF.
•
The investigator must permit study-related monitoring, audits, IRB/EC review, and
regulatory agency inspections and provide direct access to source data documents.
•
The sponsor or designee is responsible for the data management of this study
including quality checking of the data. Predefined agreed risks, monitoring thresholds,
quality tolerance thresholds, controls, and mitigation plans will be documented in a
risk management register. Additional details of quality checking to be performed on
the data may be included in a data management plan.
•
A study monitor will perform ongoing source data verification to confirm that data
entered into the eCRF by authorized site personnel are accurate, complete, and
verifiable from source documents; that the safety and rights of subjects are being
protected; and that the study is being conducted in accordance with the currently
approved protocol and any other study agreements, ICH GCP, and all applicable
regulatory requirements.
•
Records and documents, including signed ICFs, pertaining to the conduct of this study
must be retained by the investigator in the study site archive in accordance with 21
CFR 312.62(c) or for at least 5 years after the end of the study unless local regulations
or institutional policies require a longer retention period. No records may be destroyed
during the retention period without the written approval of the sponsor. No records
may be transferred to another location or party without written notification to the
sponsor.
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 Code of Federal 
Regulations Part 11-compliant electronic data capture (EDC) system on an eCRF in a timely 
fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and 
transmitted to the sponsor or designee electronically, will be integrated with the subject’s 
eCRF data in accordance with the data management plan.  
An eCRF must be completed for each enrolled subject who undergoes any screening 
procedures, according to the eCRF completion instructions. The sponsor, or CRO, will 
review the supporting source documentation against the data entered into the eCRFs to verify 
the accuracy of the electronic data. The investigator will ensure that corrections are made to 
the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The investigator will sign and date the eCRF via the EDC system’s electronic signature 
procedure. These signatures will indicate that the investigator reviewed and approved the data 
on the eCRF, data queries, and site notifications. 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 63 of 67 
Publications 
Publications will be addressed as follows:The results of this study may be published or 
presented at scientific meetings. If this is foreseen, the investigator agrees to submit all 
manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect 
proprietary information and provide comments. 
•
The sponsor will comply with the requirements for publication of study results. In
accordance with standard editorial and ethical practice, the sponsor will generally
support the publication of multicenter studies only in their entirety and not as
individual site data. In this case, a coordinating investigator will be designated by
mutual agreement.
•
Authorship will be determined by mutual agreement and in line with International
Committee of Medical Journal Editors authorship requirements.


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 64 of 67 
Appendix 6: Schedule of Assessments 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 65 of 67 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3
-2
-1
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
Demographics 
X 
Medical history 
X 
Admission to clinical 
research unit1 
X 
Discharge from clinical 
research unit2  
X 
Randomization 
X 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height/weight/BMI 
X 
Physical exam 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
Clinical chemistry  
(including cholesterol panel 
tests) 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, or 
HCVAb 
X 
12-lead safety
electrocardiogram4,8
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cardiac Telemetry 
Monitoring9 
X 
X 
X 
(Day 3) 
X 
 (Day 7) 


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 66 of 67 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3
-2
-1
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
X 
X 
X 
X 
X 
Pregnancy test6 
X 
X 
X 
Follicle -stimulating 
hormone test 
(postmenopausal females 
only) 
X 
CBP-307/placebo 
administration 
X 
X 
X 
X 
X 
X 
X 
X 
Moxifloxacin/placebo 
administration 
X 
X 
Blood sampling for PK7,8 
X 
X 
X 
X 
X 
X 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1.
Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).
2.
Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19.
3.
Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 18, and 19):
Prior to and 2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: Tympanic temperature,
respiratory rate, and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to discharge, supine vital signs (tympanic
temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): Tympanic temperature, respiratory rate, and supine pulse
rate and blood pressure.


Protocol Amendment 3 
CONFIDENTIAL 
Labcorp Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 4.0, 26 October 2021 
Page 67 of 67 
4.
12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before discharge on
Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.
5.
Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1,
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. The ECG effects
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 (supratherapeutic
concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 16.
6.
Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 29±2 days). A positive urine
pregnancy test will be confirmed with a serum pregnancy test.
7.
Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16).
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15.
8.
Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 hour postdose, ±15 minutes for ECGs and vital
sign measurements at 2 hours postdose and ±5 minutes for PK sampling at 2 hours postdose, ±5 minutes for 3 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose,
and ±30 minutes for 12 to 24, 72, and 96 hours postdose.
9.
Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 12 hours
postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended if necessary. The
start and stop date and time of the telemetry monitoring will be recorded in the eCRF.


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 1 of 9 
Summary of Amended Protocol Changes 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive Controlled Study to Investigate the Effects of CBP 307 on the QTC Interval in 
Healthy Subjects 
Protocol Amendment 2 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Protocol Amendment 2 Date: 03 August 2021 
Protocol Version: 3.0 
Investigational Medicinal Product: CBP-307 
Protocol Reference Number: CBP-307AU002 
Covance Study Number: 8463245 
IND Number: 134585 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Site: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Sponsor Signatory: 
Ping Li, MD 
Principal Investigator: 
Nicholas Farinola, MBBS 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 
________________________________________ 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 2 of 9 
The primary changes in this amendment, along with the rationale for the/each change as 
appropriate, are: 
1. Based on recommendations from the regulatory agency, the protocol was modified to add 
one oral dose administration of placebo-matched CBP-307 capsule on Day 16 for all 
subjects. This will allow for the placebo comparisons in the assay sensitivity analysis for 
Days 1 and 16. 
2. To update the protocol to exclude male and female subjects with baseline QT interval 
corrected for heart rate using Fridericia’s method (QTcF) >450 msec.  
3. To update the protocol to modify the allowable window for any history or evidence of 
alcoholism or drug/chemical abuse to within 12 months prior to check-in rather than 
2 years. 
4. To modify the windows for safety assessments at 2 hours postdose in order to provide 
additional time for the electrocardiogram (ECG) and vital signs measurements due to the 
required assessments at this timepoint. 
5. To remove the specified order for the safety assessments to allow flexibility when the 
assessments coincide with the ECG extractions. 
Minor changes: 
1. To update the company name from “Covance” to “Labcorp” as Covance is re-branding 
into the parent company Labcorp (applicable only for business units transitioned on or 
after 25 Jun 2021).  
2. To modify the protocol to include an administrative change in Medical Monitor from 
Jane Royalty to Sunu Valasseri. 
3. The protocol version and date were updated throughout the protocol. 
4. Typographical errors and formatting errors were corrected, as necessary. 
A detailed summary of changes is presented below: 
Title page and all headers 
Previously read: 
Covance 
Now reads: 
Labcorp  


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 3 of 9 
Study Identification, Medical Monitor and Statistician, page 4 
Previously read: 
Sponsor’s Medical Contact 
Jane Royalty, MD 
Covance Clinical Research Unit, Inc. 
3402 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 
Tel: 812-474-5015 
Email: jane.royalty@covance.com 
Statistician 
Wei Xiao, MS 
Covance Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 
Now reads: 
Sponsor’s Medical Contact 
Sunu Valasseri, MD 
Labcorp Clinical Research Unit Limited. 
Maidenhead 
United Kingdom 
Tel: +44 (0) 113 301 3650 
Email: S.Valasseri @labcorp.com 
Statistician 
Wei Xiao, MS 
Labcorp Drug Development Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 
 
Synopsis and Section 3.1, Study Design, paragraph 7 
Previously read: 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 16. 
The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. Pharmacokinetic 
blood samples will be collected at the following timepoints: prior to dosing and 0.5, 1, 2, 3, 4, 6, 
8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16; sample 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 4 of 9 
collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 
hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 12 to 24 hours 
postdose). Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15 (sample collection window: ±30 minutes). Subjects will be inactive and in a supine 
position for at least 10 minutes prior to and 5 minutes after each cardiodynamic ECG extraction 
timepoint, which will end immediately prior to the PK sampling. When timepoints for ECG 
extraction, safety ECGs, vital sign measurements, and blood draws coincide, procedures will be 
performed in said order. At each timepoint, up to 10 ECG replicates will be extracted from a 
5-minute time window (the last 5 minutes of the 15-minute period when the subject is 
maintained in a supine, quiet position). The ECG effects of CBP-307 will be tested on data from 
Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
Now reads: 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 16. 
The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. Pharmacokinetic 
blood samples will be collected at the following timepoints: prior to dosing and 0.5, 1, 2, 3, 4, 6, 
8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16; sample 
collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 
hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 12 to 24 hours 
postdose). Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15 (sample collection window: ±30 minutes). Subjects will be inactive and in a supine 
position for at least 10 minutes prior to and 5 minutes after each cardiodynamic ECG extraction 
timepoint, which will end immediately prior to the PK sampling. At each timepoint, up to 
10 ECG replicates will be extracted from a 5-minute time window (the last 5 minutes of the 
15-minute period when the subject is maintained in a supine, quiet position). The ECG effects of 
CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic 
concentrations versus placebo), and Day 15 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be evaluated using ECG data collected on Days -1, 1, 
15, and 16. 
Section 4.1 Inclusion Criteria, Criterion #6b 
Previously read: 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
• Normal sinus rhythm (HR between 60 bpm and 100 bpm inclusive); 
• QTcF interval ≤450 msec for males and ≤470 msec for females; 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 5 of 9 
• QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
• PR interval ≤200 msec. 
Now reads: 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
a. Normal sinus rhythm (HR between 60 bpm and 100 bpm inclusive); 
b. QTcF interval ≤450 msec for males and females; 
c. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
d. PR interval ≤200 msec. 
Section 4.2 Exclusion Criteria, Criterion #9 
Previously read: 
9. History or evidence of alcoholism or drug/chemical abuse within 2 years prior to 
check-in. 
Now reads: 
9. History or evidence of alcoholism or drug/chemical abuse within 12 months prior to 
check-in. 
Section 5.1 Investigational Products, Table 3 Study Treatments 
Previously read: 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 
400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 6 of 9 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
 
 
1 tablet 
Group 2A 
 
 
 
1 tablet 
Group 2B 
 
 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
electronic case 
report form 
(eCRF). 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 7 of 9 
Now reads: 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 
400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
1 capsule 
 
1 tablet 
Group 2A 
 
1 capsule 
 
1 tablet 
Group 2B 
 
1 capsule 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
electronic case 
report form 
(eCRF). 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 8 of 9 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
 
Appendix 6, Schedule of Assessments, CBP-307/Placebo Administration 
Previously read: 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 
to 
5 
6 
7 
to 
14 
15 
16 
17 
18 
19 
29±2 
CBP-
307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Now reads: 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 
to 
5 
6 
7 
to 
14 
15 
16 
17 
18 
19 
29±2 
CBP-
307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 


Protocol Amendment 02 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002 
Protocol Version 3.0, 03 August 2021  
Page 9 of 9 
Appendix 6, Footnote #5 
Previously read: 
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 
(baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before dosing and at 
the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the 
continuous recording prior to dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours 
postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in 
an undisturbed environment. When timepoints for ECG extraction, safety ECGs, vital signs 
assessment, and blood draws coincide, procedures will be performed in this order. The ECG 
effects of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 
(therapeutic concentrations versus placebo), and Day 15 (supratherapeutic concentrations 
versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 
15, and 16. 
Now reads: 
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 
(baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before dosing and at 
the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the 
continuous recording prior to dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours 
postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in 
an undisturbed environment. The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
tested on data from Days -1, 1, 15, and 16. 
Appendix 6, Footnote #8 
Previously read: 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours 
postdose, ±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and 
±30 minutes for 12 to 24, 72, and 96 hours postdose. 
Now reads: 
8  Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours 
postdose, ±5 minutes for 1 hour postdose, ±15 minutes for ECGs and vital sign 
measurements at 2 hours postdose and ±5 minutes for PK sampling at 2 hours postdose, 
±5 minutes for 3 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24, 72, and 96 hours postdose. 
 


TITLE PAGE 
Protocol 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, 
Placebo- and Positive-Controlled Study to Investigate the Effects of 
CBP-307 on the QTC Interval in Healthy Subjects 
Protocol Amendment 2 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Protocol Amendment 2 Date: 03 August 2021 
Protocol Version: 3.0 
Investigational Medicinal Product: CBP-307 
Protocol Reference Number: CBP-307AU002 
Labcorp Study Number: 8463245 
IND Number: 134585 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Site: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Sponsor Signatory: 
Ping Li, MD 
Principal Investigator: 
Nicholas Farinola, MBBS 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


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SPONSOR APPROVAL 
I have read the protocol and approve it: 
 
 
 
 
 
 
 
Ping Li, MD 
 
Date 
VP, Clinical Development Asia 


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INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
 
 
 
 
 
 
 
Nicholas Farinola, MBBS 
 
Date 
Principal Investigator 


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STUDY IDENTIFICATION 
Sponsor 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu 215400 
China 
Sponsor’s Study Contact 
Max Meng, BS 
Project Manager 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Tel: +86 0512 5357 7866 
Email: yhmeng@connectpharm.com 
Sponsor’s Medical Contact 
Suni Valasseri, MD 
Labcorp Clinical Research Unit Limited. 
Maidenhead 
United Kingdom 
Tel: +44 (0) 113 301 3650 
Email: S.Valasseri @labcorp.com 
Study Site  
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Principal Investigator 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 
Clinical Laboratory  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 


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Bioanalytical Laboratory 
Peter Tapley 
Director, TetraQ 
The University of Queensland 
Level 7, Block 6, RBWH 
Herston, Queensland 4029  
Australia 
Statistician 
Wei Xiao, MS 
Labcorp Drug Development, Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 


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SYNOPSIS 
Study Title 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the pharmacokinetics (PK) of CBP-307 following administration of 
therapeutic and supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on heart rate (HR), PR and QRS intervals, and T-wave morphology. 
Study Design 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only serious 
adverse events (SAEs) will be reported. After placebo administration to all subjects on 
Day -1, all adverse events (AEs), whether volunteered, elicited, or noted upon physical 
examination, will be recorded throughout the study (ie, from Day -1 until the end of the 
study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 


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Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic electrocardiogram (ECG) monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 6, 15, 
and 16 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15. Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 


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supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
Number of Subjects 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Diagnosis and Main Criteria for Inclusion 
Healthy male and female subjects aged between 18 and 60 years (inclusive) with a body mass 
index between 18.0 and 30.0 kg/m2 (inclusive). 
Investigational Medicinal Products, Dose, and Mode of Administration 
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 titrated to 0.1 mg on 
Day 2; oral capsule) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6; oral capsule) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15; oral capsule) 
• Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 
• Moxifloxacin (400 mg; oral tablet). 


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Duration of Subject Participation in the Study 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3), 21 days for the in-house 
treatment period (Days -2 to 19), and 10 ±2 days for follow-up (Day 29±2 days), in total 
approximately 59 days. 
Endpoints 
Electrocardiogram (Cardiodynamic): 
The primary cardiodynamic endpoint is the change-from-baseline QTcF (ΔQTcF). 
The secondary cardiodynamic endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
Pharmacokinetics: 
Blood samples will be collected for the analysis of plasma concentrations of CBP-307. The 
PK parameters of CBP-307 will be calculated using a model independent approach. The 
following PK parameter endpoints will be calculated: maximum observed concentration 
(Cmax), area under the concentration-time curve from time zero extrapolated to infinity 
(AUCinf), area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24), and time of the maximum observed concentration (tmax). Other noncompartmental 
parameters may be reported. 
Safety: 
Adverse events, clinical laboratory evaluations (hematology, clinical chemistry, urinalysis), 
12lead ECGs, and vital signs measurements. 
Statistical Methods 
Cardiodynamic evaluation: 
The primary analysis will be based on concentration-QTc modeling of the relationship 
between plasma concentrations of CBP-307 and change-from-baseline QTcF (∆QTcF) with 
the intent to exclude an effect of placebo-corrected ΔQTcF (ΔΔQTcF) > 10 msec at clinically 
relevant plasma levels. Placebo-corrected ΔHR, ΔPR, ΔQRS, and ∆QTcF (ΔΔHR, ΔΔPR, 
ΔΔQRS, and ∆∆QTcF) will also be evaluated at each postdosing timepoint ('by-timepoint' 


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analysis). An analysis of categorical outliers will be performed for changes in HR, PR, QRS, 
QTcF, T-wave morphology, and U-wave presence. Assay sensitivity will be evaluated by 
concentration-QTc analysis of the effect on ∆ΔQTcF of moxifloxacin using a similar model 
as for the primary analysis. 
Pharmacokinetics: 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, standard deviation, median, 
minimum, maximum geometric mean, and geometric coefficient of variation) separately by 
cohort. Individual and mean plasma CBP-307 and moxifloxacin concentration versus time 
data will be tabulated and plotted by dose level. Graphical displays of PK data may be 
provided as well.  
Pharmacokinetic/electrocardiography analyses: 
The relationship between CBP-307 plasma concentrations and the change from ∆QTcF will 
be evaluated using a linear mixed-effects modeling approach. 
Safety: 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12lead ECGs, vital signs, and physical 
examination findings will be listed. 


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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SPONSOR APPROVAL ...........................................................................................................2 
INVESTIGATOR AGREEMENT.............................................................................................3 
STUDY IDENTIFICATION .....................................................................................................4 
SYNOPSIS .................................................................................................................................6 
TABLE OF CONTENTS .........................................................................................................11 
LIST OF TABLES AND FIGURES........................................................................................14 
LIST OF ABBREVIATIONS ..................................................................................................15 
1. 
INTRODUCTION ...........................................................................................................17 
1.1. 
Disease Background...............................................................................................17 
1.2. 
Overview of CBP-307............................................................................................17 
1.2.1. 
Summary of Clinical Experience .................................................................17 
1.2.1.1. 
Safety .................................................................................................18 
1.2.1.2. 
Pharmacokinetics ...............................................................................20 
1.3. 
Overview of Moxifloxacin .....................................................................................21 
1.4. 
Study Rationale ......................................................................................................21 
1.5. 
Benefit-risk Assessment .........................................................................................22 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................22 
2.1. 
Objectives ..............................................................................................................22 
2.2. 
Endpoints ...............................................................................................................22 
2.2.1. 
Electrocardiogram Endpoints .......................................................................22 
2.2.1.1. 
Primary ...............................................................................................22 
2.2.1.2. 
Secondary ...........................................................................................22 
2.2.2. 
Pharmacokinetic Endpoints .........................................................................23 
2.2.3. 
Safety Endpoints ..........................................................................................23 
3. 
INVESTIGATIONAL PLAN ..........................................................................................23 
3.1. 
Overall Study Design and Plan ..............................................................................23 
3.2. 
Discussion of Study Design ...................................................................................26 
3.3. 
Selection of Doses in the Study .............................................................................26 
4. 
SELECTION OF STUDY POPULATION .....................................................................27 
4.1. 
Inclusion Criteria ...................................................................................................27 
4.2. 
Exclusion Criteria ..................................................................................................27 
4.3. 
Subject Number and Identification ........................................................................30 
4.4. 
Subject Withdrawal and Replacement ...................................................................30 
4.5. 
Study Termination .................................................................................................31 
5. 
STUDY TREATMENTS .................................................................................................31 
5.1. 
Investigational Products .........................................................................................31 
5.2. 
Study Treatment Administration ............................................................................33 


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5.3. 
Randomization .......................................................................................................33 
5.4. 
Blinding..................................................................................................................34 
5.5. 
Treatment Compliance ...........................................................................................34 
5.6. 
Drug Accountability...............................................................................................34 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................35 
6.1. 
Concomitant Therapies ..........................................................................................35 
6.2. 
Diet .........................................................................................................................35 
6.3. 
Smoking .................................................................................................................36 
6.4. 
Exercise ..................................................................................................................36 
6.5. 
Blood Donation ......................................................................................................36 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................36 
7.1. 
General Assessments .............................................................................................37 
7.1.1. 
Demographics ..............................................................................................37 
7.1.2. 
Medical History ...........................................................................................37 
7.2. 
Electrocardiography Assessments .........................................................................37 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording ......................................37 
7.2.1.1. 
TQT Plus Extraction Technique ........................................................37 
7.2.1.2. 
Expert Precision QT Analysis ............................................................38 
7.2.2. 
Safety 12-lead Electrocardiogram ................................................................38 
7.2.3. 
Cardiac Telemetry Monitoring ....................................................................39 
7.3. 
Pharmacokinetic Assessments ...............................................................................39 
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................39 
7.3.2. 
Analytical Methodology ..............................................................................39 
7.4. 
Safety and Tolerability Assessments .....................................................................39 
7.4.1. 
Adverse Events ............................................................................................39 
7.4.2. 
Clinical Laboratory Evaluations ..................................................................40 
7.4.3. 
Vital Signs ....................................................................................................40 
7.4.4. 
Physical Examination...................................................................................40 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................41 
8.1. 
Determination of Sample Size ...............................................................................41 
8.2. 
Analysis Populations ..............................................................................................42 
8.2.1. 
Cardiodynamic Population...........................................................................42 
8.2.2. 
Pharmacokinetic Population ........................................................................42 
8.2.3. 
Safety Population .........................................................................................42 
8.3. 
Cardiodynamic ECG Analyses ..............................................................................42 
8.4. 
Pharmacokinetic Analyses .....................................................................................45 
8.5. 
Safety Analysis ......................................................................................................46 
8.6. 
Interim Analysis .....................................................................................................46 
9. 
REFERENCES ................................................................................................................46 


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10. APPENDICES .................................................................................................................48 
Appendix 1: Adverse Event Reporting ..............................................................................49 
Appendix 2: Clinical Laboratory Evaluations ...................................................................54 
Appendix 3: Total Blood Volume ......................................................................................55 
Appendix 4: Contraception Guidance ................................................................................56 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations ............................59 
Appendix 6: Schedule of Assessments ..............................................................................63 
 


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LIST OF TABLES AND FIGURES 
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................20 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................21 
Table 3: Study Treatments .................................................................................................32 
 
Figure 1: Study Schematic .................................................................................................24 
 


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LIST OF ABBREVIATIONS 
Abbreviation Definition 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUCinf 
area under the concentration-time curve from time zero extrapolated to 
infinity 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours 
postdose 
CI 
confidence interval 
CL/F 
apparent total clearance 
Cmax 
maximum observed concentration 
CRO 
contract research organization 
CYP 
cytochrome P450 
Δ 
change-from-baseline 
ΔΔ 
placebo-corrected or placebo-adjusted change-from-baseline 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
HR 
heart rate 
HREC 
human resource ethics committee 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
IP 
investigational product 
LOESS 
locally estimated scatterplot smoothing 
LS 
least squares 
PK 
pharmacokinetic(s) 
PD 
pharmacodynamic(s) 
QD 
once daily 
QTc 
heart-corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
Rac 
accumulation ratio  
Rac(Cmax) 
accumulation ratio for Cmax 


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Rac(AUC0-24) 
accumulation ratio for AUC0-24 
SAE 
serious adverse event 
SD 
standard deviation 
SE 
standard error 
S1P1 
sphingosine-1-phosphate receptor 1 
TEAE 
treatment-emergent adverse event(s) 
t1/2 
apparent terminal elimination half-life 
tmax 
time of the maximum observed concentration 
TQT 
thorough QT 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
λZ 
apparent terminal elimination rate constant 
 
 


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1. INTRODUCTION 
Refer to the investigator’s brochure (IB)1 for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile 
of the investigational medicinal product (IMP). 
1.1. 
Disease Background 
Autoimmune diseases are serious disorders that afflict a large portion of the world 
population; most have no cures. Significant advances have been made in the development of 
novel and disease-modifying therapies, but many of these new treatments have significant 
side effects. Treatments are needed that provide better risk-to-benefit profiles than the 
existing therapeutic choices. 
T cells are important immune cells that mediate the development of autoimmune disorders. 
Migration of T cells from lymphoid tissues to the sites of inflammation is central to the 
functions of T cells, and this process is dependent on sphingosine-1-phosphate (S1P) receptor 
1 (S1P1) which is known to ameliorate a variety of autoimmune diseases in animals and 
humans. Down modulation of this receptor, using S1P1 agonists, prevents T cell egress and 
results in a reduced number of circulating lymphocytes, particularly the CD4+- and CD8+-
naïve and central-memory T cell subsets.  
1.2. 
Overview of CBP-307 
CBP-307 is an S1P1 agonist that is being developed as a treatment for autoimmune diseases 
by Suzhou Connect Biopharmaceuticals, Ltd. CBP-307 (1-(2-fluoro-4-(5-(4-isobutylphenyl)-
1,2,4-oxadiazol-3-yl) benzyl) azetidine-3-carboxylic acid hemihydrate) is a potent, selective, 
small-molecule agonist of S1P1 and S1P5 receptors. Cell-based assays have confirmed 
CBP-307 induces internalization of S1P1 from the cell surface. This is consistent with the 
known mechanism of action of other S1P1 agonists, in that they down-modulate S1P1 and 
inhibit lymphocyte egress from lymphoid tissues.  
1.2.1. 
Summary of Clinical Experience 
The Phase 1 development of CBP-307 comprised 2 completed studies in healthy subjects: 
• A single and multiple ascending dose study to evaluate the safety and tolerability of 
CBP-307 including pharmacokinetic (PK), pharmacodynamic (PD), and food-effect 
assessments (Study CBP-307AU001) 
• A single-dose and multiple-dose, and fixed-dose titration study to evaluate the safety 
and tolerability of CBP-307 including PK and PD (Study CBP-307CN001) 
Currently, CBP-307 is being evaluated in 2 Phase 2 studies:  
• Ongoing multicenter study in subjects with moderate to severe ulcerative colitis 
(Study CBP-307CN002) to compare the clinical efficacy by evaluating the clinical 
response to CBP-307 versus placebo and the clinical remission and mucosal healing 


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achieved by CBP-307 versus placebo and to compare the clinical safety and 
tolerability of CBP-307 with those of placebo. 
• Ongoing study in subjects with moderate to severe Crohn’s disease compares clinical 
efficacy by evaluating the clinical response to CBP-307 versus placebo and the 
clinical remission and mucosal healing achieved by CBP-307 versus placebo and to 
compare the clinical safety and tolerability of CBP-307 with those of placebo. 
1.2.1.1. 
Safety 
Study CBP-307AU001 
A total of 44 healthy subjects were enrolled in the study. There were 28 subjects evaluated 
using the single-dose regimen (0.1, 0.25, 0.5, and 2.5 mg CBP-307) of which 21 subjects 
received CBP-307 and 7 subjects received placebo. Another 16 healthy subjects were 
evaluated using the multiple-dose regimen (0.15 and 0.25 mg CBP-307 given once daily 
[QD] for 28 consecutive days) of which 12 subjects received CBP-307 and 4 subjects 
received placebo. 
Overall, no unexpected safety signals were identified and no deaths occurred in this study. 
For the single-dose regiment, no subjects were discontinued due to a treatment-emergent AE 
(TEAE). In the multiple-dose regimen, there were 2 subjects who were discontinued from the 
study (due to increased alanine transaminase and second degree AV block [not considered to 
be clinically significant, as judged by the investigator]). All TEAEs resolved by the end of 
the study. 
In the single-dose regimen groups, TEAEs were reported in 12 of 21 subjects (57.1%) treated 
with CBP-307 and in 3 of 7 subjects (42.8%) treated with placebo. Most (91.7%) of the 
TEAEs in these subjects were mild in severity. The most common TEAEs in the 
CBP-307-treated groups were headache (28.6%); dizziness (19.0%); and bradycardia (9.5%). 
Bradycardia was reported only in 2 subjects receiving the highest (2.5 mg) CBP-307 dose. 
One subject had a serious adverse event (SAE) of bradycardia (associated with transient 
asystole) following a single dose of 2.5 mg CBP-307. 
In the multiple-dose regimen groups, CBP-307 at doses of 0.15 and 0.25 mg QD was 
generally well tolerated over the 28 days of dosing. Treatment-emergent AEs were reported 
in 11 of 12 subjects (91.7%) in the CBP-307 groups and 2 of 4 subjects (50.0%) in the 
placebo groups. Most (83.3%) TEAEs were mild in severity. The most common TEAEs in 
the 2 CBP-307 groups were headache (50.0%), and fatigue, nausea, and musculoskeletal pain 
(16.7% each). The incidences of these TEAEs were similar in both CBP-307-treated groups. 
No SAEs were reported for subjects in the multiple-dose regimen. 
Study CBP-307CN001 
A total of 30 eligible subjects completed 3 CBP-307 dose groups in ascending order of dose 
after randomization (in a ratio of 1:1:1): Group A (0.1 mg), Group B (0.2 mg), and Group C 
(0.3 mg). Each dose group consisted of 10 subjects, including 8 subjects receiving the 
investigational drug and 2 subjects receiving placebo by random assignment. The 
administration started from the dose of 0.1 mg. The subjects in this group received a single 


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dose of CBP-307 or placebo and were followed up for safety and tolerance within the next 
7 days. Then the subjects received 0.1 mg CBP-307 or placebo QD for 14 consecutive days 
and were followed up for safety and tolerance within the next 7 days. Dose escalation did not 
occur until the review of the single-dose regimen safety data from the 6 subjects in the 
previous dose cohort, and the safety data did not meet the termination criteria. The subjects in 
the dose of 0.3 mg received fixed-dose titration regimen, ie, 0.05 mg CBP-307 or placebo QD 
for 3 consecutive days; 0.1 mg CBP-307 or placebo QD for 2 consecutive days; 0.2 mg 
CBP-307 or placebo QD for 2 consecutive days; finally, 0.3 mg CBP-307 or placebo QD for 
14 consecutive days, and the subjects were followed up for safety and tolerance within the 
next 7 days. 
Overall, no unexpected safety signals were identified, and there were no deaths, SAEs, or 
AEs leading to the subject’s early withdrawal from the study after administration of 
CBP-307. In the safety set, a total of 29 subjects (8 in Group A, 100%; 8 in Group B, 100%; 
8 in Group C, 100% and 5 in placebo group, 83.3%) experienced TEAEs. 
During the single-dose period, a total of 14 subjects (5 of 8 in Group A, 62.5%; 6 of 8 in 
Group B, 75%, and 3 of 4 in placebo group, 75%) developed AEs. The incidence of TEAEs 
in Group A was generally similar to the placebo group. Among TEAEs in Group B, the 
incidence of AEs related to abnormalities in investigations was higher than that in placebo 
group, including lymphocyte count decreased (12.5%), white blood cell (WBC) count 
decreased (12.5%), neutrophil count decreased (12.5%), alanine aminotransferase increased 
(25%), and gamma-glutamyltransferase increased (12.5%), and aspartate aminotransferase 
increased (12.5%). Additionally, 1 subject experienced heart rate (HR) decreased (12.5%). 
During dose-titration period, 2 subjects (2 of 8 in Group C, 25%) experienced TEAEs. The 
TEAEs reported in Group C during the titration period included cough (12.5%) and increased 
upper airway secretion (12.5%). There were no TEAEs in the placebo group during this 
period. 
During repeated-dose period, a total of 28 subjects (8 of 8 in Group A, 100%; 8 of 8 in Group 
B, 100%; 8 of 8 in Group C, 100%; and 4 of 6 in placebo group, 66.7%) experienced AEs. 
The most frequent TEAE in Group A was upper respiratory tract infection (37.5%) compared 
with placebo group; the most frequent TEAEs in Group B and Group C included decreased 
lymphocyte count (Group B, 87.5%; Group C, 100.0%), WBC count (Group B, 87.5%; 
Group C, 62.5%), and neutrophil count (Group B, 50%; Group C, 12.5%). The TEAEs noted 
in Group B during the repeated-dose period also included increased alanine aminotransferase 
(25%), gamma-glutamyltransferase (37.5%), and aspartate aminotransferase (12.5%), upper 
respiratory tract infection (12.5%), influenza (12.5%), chest pain (12.5%), lethargy (25%), 
and neck pain (12.5%); TEAEs in Group C during the repeated-dose period also included 
increased alanine aminotransferase (25%), decreased HR (12.5%), and mouth ulcer (12.5%); 
the TEAEs in placebo group included increased transaminase (16.7%), prolonged activated 
partial thromboplastin time (1/6, 16.7%), decreased hemoglobin (16.7%), upper respiratory 
tract infection (16.7%), diarrhea (16.7%), dizziness (16.7%), and palpitations (16.7%). 
Study CBP-307CN002 
This study is ongoing and there are no safety data available.  


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Study CBP-307CN003 
This study is ongoing and there are no safety data available.  
1.2.1.2. 
Pharmacokinetics 
CBP-307 given orally as a single dose was readily absorbed; drug concentrations peaked at 
approximately 6 hours after administration, with an elimination apparent terminal elimination 
half-life (t1/2) of approximately 25 hours (range of 23 to 29 hours). The time to maximum 
observed concentration (Cmax) in the blood was delayed from 6 hours to approximately 
10 hours when CBP-307 was given with a high-fat diet. Food consumption also increased 
exposure (Table 1). 
For the single-dose administration, CBP-307 exposure (based on Cmax and area under the 
concentration-time curve [AUCs]) increased with increasing dose following a single-dose 
administration (Table 1).  
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Single-Dose 
Regimen PK 
Parameters 
Mean CBP-307 Single Dose ± SEM (n) 
0.1 mg 
0.25 mg 
0.5 mg 
(fasted) 
0.5 mg (fed)a 
2.5 mg 
AUClast 
(ng*h/mL) 
13.4 ± 3.54 
(n = 6) 
45.1 ± 5.25 
(n = 6) 
160 ± 22.8 
(n = 6) 
290 ± 28.1 
(n = 6) 
550 ± 96.3 
(n = 3) 
AUCinf 
(ng*h/mL) 
ND 
63.7 ± 2.14 
(n = 3) 
214 ± 58.3 
(n = 3) 
355 ± 44.3 
(n = 5) 
710 ± 164 
(n = 2) 
Cmax 
(ng/mL) 
0.537 ± 0.0931 
(n = 6) 
1.53 ± 
0.0935 
(n = 6) 
4.84 ± 0.706 
(n = 6) 
8.58 ± 1.11 
(n = 6) 
19.0 ± 3.55 
(n = 3) 
tmax 
(hours) 
7.33 ± 1.33 
(n = 6) 
5.33 ± 0.99 
(n = 6) 
5.00 ± 0.86 
(n = 6) 
10.67 ± 2.72 
(n = 6) 
6.00 ± 2.00 
(n = 3) 
t1/2 
(hours) 
ND 
23.3 ± 1.70 
(n = 3) 
28.8 ± 1.28 
(n = 3) 
26.0 ± 1.17 
(n = 5) 
22.8 ± 3.96 
(n = 2) 
Abbreviations: AUCinf = area under the curve at infinity; AUClast = area under the curve at the last time point; 
Cmax = maximum concentration; h = hour(s); mg = milligram(s); ND = not determinable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SEM = standard error of the mean; T1/2 = elimination half-life; Tmax = time to maximum 
concentration.  
a Study Part 1b: Cohort 3 from Part 1a returned to receive a single oral dose of CBP-307 at 0.5 mg under fed conditions. 
Source: Final report for Study CBP-307AU001. 
For the repeated-dose administration of CBP-307, the Cmax and AUCs increased with the 
higher administered dose (Table 2). At the steady-state timepoint on Day 28, the median 
CBP-307 tmax was 4 to 6 hours. The average t1/2 was similar, ranging 44 to 49 hours, and 
there were no dose-dependent changes in t1/2 within the dose range. The t1/2 was slightly 
prolonged after repeated-dose administration when compared with that after a single-dose 
administration. Moderate accumulation of CBP-307 (approximately 3 times the levels 


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following a single dose) was noted in plasma after QD administration for 14 consecutive 
days. 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Multiple-Dose 
Regimen PK 
Parameters 
Multiple-Dose Cohort 1  
CBP-307 Dosing, mg (± SD) (n) 
Multiple-Dose Cohort 2  
CBP-307 Dosing, mg (± SD) (n) 
Day 1 
0.1  
Day 28 
0.25  
Day 1 
0.15  
Day 28 
0.15  
AUC0-24 
(ng*h/mL) 
24.5 ± 3.26 
(n = 5) 
125 ± 12.4 
(n = 4) 
26.3 ± 7.45 
(n = 5) 
79.7 ± 27.3 
(n = 6) 
AUClast 
(ng*h/mL) 
NA 
203 ± 21.9 
(n = 4) 
NA 
131 ± 44.7 
(n = 6) 
Cmax 
(ng/mL) 
1.45 ± 0.214 
(n = 5) 
6.30 ± 0.588 
(n = 4) 
1.32 ± 0.422 
(n = 6) 
4.23 ± 1.45 
(n = 6) 
tmax 
(hours) 
6.80 ± 1.50 
(n = 5) 
6.50 ± 1.50 
(n = 4) 
5.00 ± 0.68 
(n = 6) 
4.33 ± 0.33 
(n = 6) 
Abbreviations:  AUC0-24 = area under the curve from time 0 to 24 hours; AUClast = area under the curve at the last time 
point; Cmax = maximum concentration; mg = milligram(s); NA = not applicable; ng/mL = nanogram(s) per milliliter; PK = 
pharmacokinetic; SD = standard deviation; Tmax = time to maximum concentration. 
Source: Final report for Study CBP-307AU001. 
1.3. 
Overview of Moxifloxacin 
Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic that binds to and inhibits the 
hERG IKr α subunit and causes a mean increase of the QTc interval of 6 ms after a single 
400-mg oral dose. Moxifloxacin is commonly used as a positive control in thorough QT 
(TQT) studies to satisfy the requirements of International Council for/Conference on 
Harmonisation (ICH) E14. 
Refer to the regional manufacturer package insert of AVELOX (moxifloxacin hydrochloride) 
tablets for additional information.2 
1.4. 
Study Rationale 
Regulatory guidance (ICH E14) has emphasized the need to obtain clear robust data on the 
effect of new chemical entities on electrocardiogram (ECG) parameters with focus on cardiac 
repolarization as measured by the QTc duration. Though many Phase 1, 2, and 3 trials may be 
conducted they usually have an insufficient sample size, infrequent sampling of ECG data, or 
the use of inadequate controls to overcome the high rate of spontaneous change in QTc 
duration. This has resulted in regulatory guidance recommending a dedicated or thorough 
trial to define the ECG effects of new drugs. 
This study will be done in healthy subjects to eliminate variables known to have an effect on 
ECG parameters (concomitant drugs, diseases, etc.). A supratherapeutic dose of CBP-307 is 
required to mimic the exposure in healthy subjects that may occur in the target population 
under the worst of circumstances (eg, concomitant use of cytochrome P450 [CYP]3A4 


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inhibitor, concomitant liver disease, presence of heart disease, taking more than the clinical 
dose prescribed) and to allow for PK to QTc modeling to assess the effect of drug 
concentration on cardiac repolarization. 
1.5. 
Benefit-risk Assessment 
Healthy subjects in the current study will not receive any health benefit (beyond that of an 
assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from the collection of blood samples and other study 
procedures. More information about the known and expected benefits, risks, and reasonably 
anticipated AEs associated with CBP-307 may be found in the IB.1  
2. OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the PK of CBP-307 following administration of therapeutic and 
supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on HR, PR and QRS intervals, and T-wave morphology. 
2.2. 
Endpoints 
2.2.1. 
Electrocardiogram Endpoints 
2.2.1.1. 
Primary 
The primary endpoint is the change-from-baseline QTcF (ΔQTcF). 
2.2.1.2. 
Secondary  
The secondary endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 


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• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
2.2.2. 
Pharmacokinetic Endpoints 
Pharmacokinetic parameters of CBP-307 will be determined if data allows: 
• area under the concentration‑time curve from time zero extrapolated to infinity 
(AUCinf) 
• area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24) 
• maximum observed concentration (Cmax) 
• time of the maximum observed concentration (tmax) 
Other PK parameters may also be reported. 
2.2.3. 
Safety Endpoints 
The safety outcome measures for this study are as follows: 
• incidence and severity of AEs 
• incidence of laboratory abnormalities, based on hematology, clinical chemistry, and 
urinalysis test results 
• 12-lead ECG parameters 
• vital signs measurements. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only SAEs will be 
reported. After placebo administration to all subjects on Day -1, all AEs, whether 


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volunteered, elicited, or noted upon physical examination, will be recorded throughout the 
study (ie, from Day -1 until the end of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 
Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec.  
An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 
32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 
16 subjects. Subjects will be randomized to receive a treatment sequence that includes 4 treatments (CBP-307 therapeutic 
dose, CBP-307 supratherapeutic dose, moxifloxacin, or placebo [matched to CBP-307 or moxifloxacin]); assigned study 
treatments will be administered on Day 1, Day 2, Days 3 to 6, Days 7 to 15, and Day 16. Dosing details are provided in 
Table 3. Blood samples for pharmacokinetic analysis will be collected predose and at each postdose cardiodynamic 
electrocardiogram timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. An 
end-of-study visit will occur on Day 29±2 days. 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1
Day 2


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Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at 
least 25 hours prior to the administration of study treatments on Day 1 and continue through 
24 hours after the administration of study treatments on Days 1, 6, 15, and 16 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK 
analysis will be collected predose and at each postdose cardiodynamic ECG timepoint. 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 


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The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 
3.2. 
Discussion of Study Design 
The purpose of this study is to evaluate the potential for CBP-307 to cause QT prolongation. 
As CBP-307 exposure affects heart rate, the primary endpoint for this study will be the QTcF. 
The study will be randomized and double-blind because randomization eliminates 
confounding by baseline variables and blinding eliminates confounding by co-interventions, 
thus eliminating the possibility that the observed effects of the intervention are because of 
differential use of other treatments.  
The sample size for this study is based on a formal statistical power calculation. 
Conducting the study in healthy subjects mitigates the potential confounding effects of the 
disease state and concomitant medications. Both male and female subjects will be included to 
eliminate similar known ECG variability effects. 
Additionally, because food has been shown to alter the PK of CBP-307, subjects will be 
fasted at least 10 hours prior to dose administration and remain fasted for 4 hours postdose on 
the days when PK samples are collected. 
Pharmacokinetic assessments of CBP-307 concentrations in plasma will be evaluated during 
the study. The timepoints for the PK sample collections are based on previous studies and are 
considered adequate to allow for the characterization of the drug’s PK after oral dosing. 
Furthermore, the chosen PK sample collection for CBP-307 is anticipated to be sufficient to 
allow reasonable estimation of t1/2 during the terminal elimination phase.  
3.3. 
Selection of Doses in the Study 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To 
carefully monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 
doses will be up-titrated as follows: subjects will receive a starting dose of 0.05 mg CBP-307 
on Day 1 followed by an up-titrated dose of 0.1 mg on Day 2 and a dose of 0.2 mg on 
Days 3 to 6. Prior clinical experience with CBP-307 has not demonstrated clinically 
significant abnormalities in laboratory test results in the majority of subjects or a dose-
response relationship for safety based on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the 
characteristics of the study design with the safety of healthy subjects. Testing of CBP-307 at 
substantial multiples of the anticipated maximum therapeutic exposure is not clinically 
warranted due to the known safety and tolerability profile of CBP-307.  


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Further details are provided in the IB.1 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the screening visit unless otherwise 
stated: 
1. Males or females, of any race, between 18 and 60 years of age, inclusive. 
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive. 
3. In good health, determined by no clinically significant findings from medical history, 
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) at screening and 
confirmed at check-in as assessed by the investigator (or designee). 
4. Females will not be pregnant or lactating, and females of childbearing potential and 
males will agree to use contraception as detailed in Appendix 4. Negative pregnancy 
test for females of childbearing potential at screening (blood test) and check-in (urine 
test). 
5. Supine diastolic blood pressure between 60 and 90 mmHg and systolic blood pressure 
between 90 and 140 mmHg (inclusive) at screening on a single measurement 
(confirmed by a single repeat, if necessary) following at least 5 minutes of rest. 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
a. Normal sinus rhythm (HR between 60 bpm and 100 bpm inclusive); 
b. QTcF interval ≤450 msec for males and females; 
c. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
d. PR interval ≤200 msec. 
7. Has serum potassium, calcium, and magnesium levels within the normal reference 
range at screening, as judged by the investigator. 
8. Able to swallow multiple tablets (based on subject’s verbal confirmation). 
9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 
4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
screening visit unless otherwise stated: 
1. Subject is mentally or legally incapacitated or has had significant history of recent 
mental health issues requiring medication and/or hospitalization at the time of the 
screening visit or expected during the conduct of the study. 


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2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, 
hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the 
investigator (or designee). Note: Childhood asthma that is considered recovered or 
seasonal allergies that are not currently active or requiring treatment are allowed. 
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, unless approved by the investigator (or designee). 
4. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, 
related compounds, or inactive ingredients. 
5. History of significant multiple and/or severe allergies (eg, latex allergy, band-aids, 
adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant 
intolerability to prescription or nonprescription drugs. 
6. History of stomach or intestinal surgery or resection that would potentially alter 
absorption and/or excretion of orally administered drugs within 6 months prior to the 
first dose of study drug (uncomplicated appendectomy and hernia repair will be 
allowed). 
7. History or presence of: 
a. Hypokalemia, in the opinion of the investigator (or designee); 
b. Risk factors for Torsades de Pointes (eg, heart failure, cardiomyopathy, or 
family history of Long QT Syndrome); 
c. Sick sinus syndrome, second, or third degree atrioventricular block, 
myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged 
QT interval, or conduction abnormalities; 
d. Repeated or frequent syncope or vasovagal episodes; 
e. Hypertension, angina, bradycardia, or severe peripheral arterial circulatory 
disorders. 
8. Clinically significant abnormalities (as judged by the investigator in laboratory tests 
results [out-of-range results confirmed on repeat]), including but not limited to the 
following parameters: 
a. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or 
total bilirubin greater than 1.5 × upper limit of normal; 
b. hemoglobin <10 g/dL, WBC <3.0 ×109/L, neutrophils <1.5 ×109/L, 
lymphocytes <0.8 ×109/L and platelets <100 ×109/L or >1200 × 109/L; 
9. History or evidence of alcoholism or drug/chemical abuse within 12 months prior to 
check-in. 
10. Alcohol consumption of >10 units per week for males and females. One unit of 
alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill 
(25 mL) of spirits. 
11. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) 
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12. Positive hepatitis panel, positive syphilis test, and/or positive human 
immunodeficiency virus test (Appendix 2).  
13. Participation in a clinical study involving administration of an investigational drug 
(new chemical entity) in the past 28 days prior to the first dose of study treatment on 
Day 1. The 28-day window will be derived from the date of the last blood collection 
or dosing, whichever is later, in the previous study to Day 1 of the current study. 
14. Participation in a previous clinical study where subjects received CBP-307. 
15. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 
28 days prior to first dose of study treatment on Day 1. 
16. Use or intend to use any prescription medications/products within 14 days prior to 
first dose of study drug (Day 1) and throughout the study, unless deemed acceptable 
by the investigator (or designee). Note: For females only, the use hormonal 
contraception, hormone replacement therapy or oral, implantable, transdermal, 
injectable, or intrauterine hormonal contraceptives within 14 days prior to Day 1 is 
not acceptable, except for Mirena®. 
17. Use or intend to use any drugs known to be significant inhibitors or inducers of CYP 
enzymes and/or P-gp, including St. John’s Wort, for days prior to the first dose of 
study drug and throughout the study. Appropriate sources will be consulted by the 
investigator or designee to confirm the lack of PK/PD interaction with the study drug. 
18. Use or intend to use slow-release medications/products considered to still be active 
within 14 days prior to check-in, unless deemed acceptable by the investigator (or 
designee). 
19. Use or intend to use any nonprescription medications/products including antacids, 
vitamins (especially those containing magnesium, aluminum, iron, or zinc), minerals, 
and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to 
check-in, unless deemed acceptable by the investigator (or designee). 
20. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or 
positive cotinine at screening or check-in.  
21. Has been on a diet incompatible with the on-study diet (including an extreme diet 
which resulted in a significant weight change for whatever reason), in the opinion of 
the investigator, within the 28 days prior to the first dose of study treatment, and 
throughout the study. 
22. Consumption of caffeine/xanthine-containing foods or beverages within 48 hours 
prior to check-in until discharge. 
23. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages 
within 7 days prior to check-in. 
24. Receipt of blood products within 2 months prior to check-in. 
25. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to 
screening, or platelets from 6 weeks prior to screening. 
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27. Subjects who, in the opinion of the investigator (or designee), should not participate 
in this study. 
4.3. 
Subject Number and Identification 
Subjects will have a unique identification number used at screening. Eligible subjects will be 
assigned a subject number prior to the first dosing occasion. Assignment of subject numbers 
will be in ascending order and no numbers will be omitted (eg, Subjects 0101, 0102, 0103). 
The screening number will be used on all safety samples throughout the study. Replacement 
subjects (Section 4.4) will be assigned a subject number corresponding to the number of the 
subject he/she is replacing plus 1000 (eg, Subject 1101 replaces Subject 0101). 
Subjects will be identified by screening identification number or subject number only on all 
study documentation. A list identifying the subjects by subject number will be kept in the site 
master file. 
4.4. 
Subject Withdrawal and Replacement 
A subject is free to withdraw their informed consent from the study at any time or they may 
be withdrawn at any time at the discretion of the investigator or the sponsor for safety, 
behavioral, or the inability of the subject to comply with the protocol-required visits or 
procedures. In addition, a subject will be withdrawn from dosing if any of the following 
criteria are met: 
• change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the investigator (or designee) 
• noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the investigator (or designee) 
• any clinically relevant sign or symptom that, in the opinion of the investigator (or 
designee), warrants subject withdrawal. 
If a subject is withdrawn from dosing, the sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic case report form (eCRF). If 
a subject is withdrawn from the study, efforts will be made to perform all follow-up 
assessments, if possible (Appendix 6). Other procedures may be performed at the 
investigator’s (or designee’s) and/or sponsor’s discretion. If the subject is in-house, these 
procedures should be performed before the subject is discharged from the clinic. The 
investigator (or designee) may also request that the subject return for an additional follow-up 
visit. All withdrawn subjects will be followed until resolution of all their AEs or until the 
unresolved AEs are judged by the investigator (or designee) to have stabilized. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, effort should be made to document subject outcome, if possible. 
The investigator should inquire about the reason for withdrawal, request the subject to return 
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Subjects who are withdrawn for reasons not related to study treatment may be replaced 
following discussion between the investigator and the sponsor. Subjects withdrawn as a result 
of AEs thought to be related to the study treatment will generally not be replaced. 
4.5. 
Study Termination 
The study may be discontinued at the discretion of the investigator (or designee), sponsor, or 
sponsor’s medical monitor if any of the following criteria are met: 
• investigator decides to terminate the study due to safety concerns such as AEs 
unknown to date (ie, not previously reported in any similar investigational study drug 
trial with respect to their nature, severity, and/or duration) 
• increased frequency, severity, and/or duration of known, anticipated, or previously 
reported AEs (this may also apply to AEs defined at check-in as baseline signs and 
symptoms) 
• medical or ethical reasons affecting the continued performance of the study 
• difficulties in the recruitment of subjects 
• cancelation of drug development 
• sponsor requests for termination (eg, due to financial or management reasons, etc.) 
under the premise to fully protect the safety and rights of subjects  
• health authority or ethics committee (EC) orders the termination of the trial for any 
reason. 
Definition of end-of-treatment and end-of-study  
• end-of-treatment is completion of safety follow-up or withdrawal from the study. 
End-of-study is the last visit by the last subject. 
5. STUDY TREATMENTS 
Study treatments are defined as any investigational product (IP), non-investigational product 
(non-IP), placebo, or medical device intended to be administered to a study subject according 
to the study protocol. 
Note that in several countries, IP and non-IP are referred to as IMP and non-IMP, 
respectively. 
5.1. 
Investigational Products 
The details regarding the storage, preparation, destruction, and administration of each 
treatment shown in Table 3 will be provided in a separate document. Approximately 
64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 
and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and 
each sub-group will be randomized with 16 subjects.  
 


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Table 3: Study Treatments 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
1 capsule 
 
1 tablet 
Group 2A 
 
1 capsule 
 
1 tablet 
Group 2B 
 
1 capsule 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
electronic 
case report 
form (eCRF). 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
 
All supplies of the IMP, both bulk and subject-specific, will be stored in accordance with the 
manufacturer’s or pharmacy’s instructions. Until dispensed to the subjects, the study 
treatments will be stored at the study site in a location that is locked with restricted access. 
5.2. 
Study Treatment Administration 
Each dose of study treatment (CBP-307, placebo, or moxifloxacin) will be administered 
orally following an overnight fast of at least 10 hours, with approximately 240 mL of room 
temperature water. Additionally, because food has been shown to alter the PK of CBP-307, 
subjects will be fasted at least 10 hours prior to dose administration and remain fasted for 
4 hours postdose on the days when PK samples are collected. 
Subjects will be dosed in numerical order while sitting or standing but not be permitted to lie 
supine for 2 hours after treatment administration, except as necessitated by the occurrence of 
an AE(s) and/or study procedures. 
5.3. 
Randomization 
This is a double-blind randomized study. Subjects will be randomized to one of the treatment 
sequences before administration of the first dose of study treatment. A randomization list will 
be generated by a statistician using a computer-generated pseudo-random permutation 
procedure. The randomization date is to be documented in the subject’s medical record and 
on the enrollment eCRF. A computer-generated randomization schedule and emergency 
code-break envelopes will be provided to the study site. Randomization details will be 
included in the randomization specification. 


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5.4. 
Blinding 
This is a double-blinded study. The following controls will be employed to maintain the 
double-blind status of the study: 
• The placebo will be identical in appearance to CBP-307 or moxifloxacin. 
• The investigator and other members of staff involved with the study will remain 
blinded to the treatment randomization code during the assembly procedure. 
• Interim bioanalytical data will be provided to Labcorp Early Clinical Biometrics in a 
blinded manner. 
To maintain the blind, the investigator will be provided with a sealed randomization code for 
each subject, containing coded details of the treatment. These individually sealed envelopes 
will be kept in a limited access area that is accessible 24 hours a day. If, in order to manage 
subject safety or to support dose escalation decisions (in the event of possibly 
treatment-related SAEs or severe AEs), the decision to unblind resides solely with the 
investigator. Whenever possible, and providing it does not interfere with or delay any 
decision in the best interest of the subject, the investigator will discuss the intended 
code-break with the sponsor. If it becomes necessary to break the code during the study, the 
date, time, and reason will be recorded in the subject's source data and on the individual 
envelope and will be witnessed by a second person. 
5.5. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of suitably qualified study site 
staff. 
• Immediately after dose administration, visual inspection of the mouth and hands will 
be performed for each subject. 
• At each dosing occasion, a predose and postdose inventory of IMP will be performed.   
5.6. 
Drug Accountability 
The investigator (or designee) will maintain an accurate record of the receipt of study 
treatments (CBP-307, moxifloxacin, placebo-matched CBP-307, and placebo-matched 
moxifloxacin) received. In addition, an accurate drug disposition record will be kept, 
specifying the amount dispensed to each subject and the date of dispensing. This drug 
accountability record will be available for inspection at any time. At the completion of the 
study, the original drug accountability record will be available for review by the sponsor 
upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused 
assembled unit doses will be retained until the completion of the study. 


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At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the 
study site’s pharmacy (RAH Pharmacy), per the sponsor’s written instructions. If destruction 
is authorized to take place at the study site’s pharmacy, the investigator must ensure that the 
materials are destroyed in compliance with applicable environmental regulations and 
institutional policy. All study drug destructions must be adequately documented. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects will refrain from the use of any prescription or nonprescription medications/products 
during the study until the follow-up visit, unless the investigator (or designee) and/or sponsor 
have given their prior consent. Medications taken within 28 days before study treatment 
administration will be documented as a prior treatment. Treatments taken after study 
treatment administration will be documented as concomitant treatments. 
Paracetamol/acetaminophen (2 g/day for up to 3 consecutive days) is an acceptable 
concomitant medication. The administration of any other concomitant medications during the 
study is prohibited without prior approval of the investigator (or designee), unless its use is 
deemed necessary for the treatment of an AE. Any medication taken by a subject during the 
course of the study and the reason for its use will be documented in the source data.  
Females will refrain from the use of hormone replacement therapy and oral, implantable, 
transdermal, injectable, or intrauterine hormonal contraceptives (with the exception of 
Mirena®) during the study until the follow-up visit (Appendix 4). 
6.2. 
Diet 
While confined at the study site, subjects will receive a standardized diet at scheduled times 
that do not conflict with other study-related activities. Subjects will be fasted overnight (at 
least 10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be 
allowed from 7 days prior to check-in until follow-up visit on Day 29±2 days. 
Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 19. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge 
on Day 19 and alcohol intake will be limited to a maximum of 2 units/day on all other days, 
whilst not at the study site, from screening to 72 hours prior to the follow-up visit on 
Day 29±2 days.  


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6.3. 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 
3 months prior to check-in until the follow-up visit. 
6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 29±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 3 months prior to screening, 
plasma from 2 weeks prior to screening, and platelets from 6 weeks prior to screening until 
3 months after the follow-up visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. The order of 
priority for scheduling procedures around a timepoint is (in descending order of priority): 
• dosing 
• continuous ECG extraction window 
• pharmacokinetic blood samples 
• safety assessments  
• any other procedures. 
This study includes a screening period (Day -28 to Day -3), a treatment period (Days -2 to 
19), and a follow-up period (Day 29 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2) 
or baseline (Day -1 predose) will only be considered exclusionary if judged applicable by the 
investigator. For confirmation of enrollment eligibility based on pulse rate, the pulse rate 
assessed by vital signs, rather than the 12-lead ECG, will be used. For all subjects, the 
screening, check-in, or baseline blood pressure, pulse rate, and respiratory rate may be 
repeated after 5 to 10 minutes if the initial reading is believed to be atypical for the subject. 


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7.1. 
General Assessments 
7.1.1. 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in order 
to study their possible association with subject safety and treatment effectiveness. 
7.1.2. 
Medical History 
At the timepoint specified in Appendix 6, the investigator or designee will collect a complete 
medical and surgical history. Medical history will include information on the subject’s 
concurrent medical conditions and any events occurring prior to the first dose of study 
treatment. All findings will be recorded on the medical history eCRF. 
7.2. 
Electrocardiography Assessments 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording 
Continuous 12-lead digital ECG recording will be performed as specified in Appendix 6. All 
ECG data will be collected using a Holter (or Mortara Surveyor) ECG continuous 12-lead 
digital recorder. The 12-lead Holter (or Mortara Surveyor) ECG equipment will be supplied 
and supported by ERT (eResearch Technology Inc., Philadelphia, PA). The continuous 
12-lead digital ECG data will be stored onto SD memory cards.  
The ECGs to be used in the analyses will be selected by predetermined timepoints as defined 
in Appendix 6 and will be read centrally by ERT (eResearch Technology Inc., Philadelphia, 
PA). The following principles will be followed in ERT’s core laboratory: 
• ECG analysts are blinded to the subject, visit, and treatment allocation. 
• Baseline and on-treatment ECGs for a particular subject will be over-read on the same 
lead and will be analyzed by the same reader. 
The primary analysis lead is lead II. If lead II is not analyzable, then the primary lead of 
analysis will be changed to another lead for the entire subject data set. 
The 12-lead ECGs will be extracted in up to 10 replicates at the predefined timepoints and 
subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 minutes 
after each nominal time. 
7.2.1.1. 
TQT Plus Extraction Technique 
Ten 14-second digital 12-lead ECG tracings will be extracted from the continuous Holter (or 
Mortara Surveyor) recordings using the ‘TQT Plus method’, a computer-assisted and 
statistical process utilized by ERT. The method enables extraction of ECGs with the lowest 
HR variability and noise within the protocol-specified extraction time window (eg, the HR 
and QT changes from beat-to-beat in the range of <10%). At each protocol-specified 
timepoint, 10 ECG replicates will be extracted from a 5-minute “ECG window” (typically, 


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the last 5 minutes of the 15-minute period when the subject is maintained in a supine, quiet 
position). 
7.2.1.2. 
Expert Precision QT Analysis 
Expert precision QT analysis will be performed on all analyzable (non-artifact) beats in the 
10 ECG replicates. Statistical quality control procedures are used to review and assess all 
beats and identify “high” and “low” confidence beats using several criteria, including: 
• QT or QTc values exceeding or below certain thresholds (biologically unlikely). 
• RR values exceeding or below certain thresholds (biologically unlikely). 
• Rapid changes in QT, QTc, or RR from beat-to-beat. 
Measurements of all primary ECG parameters (QT, QTc, RR) in all recorded beats of all 
replicates that are deemed “high confidence” will be performed using COMPAS software. 
All low-confidence beats will be reviewed manually and adjudicated using pass-fail criteria. 
The final QC assessment will be performed by a cardiologist. The beats found acceptable by 
manual review will be included in the analysis. The median QT, QTc, and RR values from 
each extracted replicate will be calculated, and then the mean of all available medians from a 
nominal timepoint will be used as the subject’s reportable value at that timepoint. 
Categorical T-wave morphology analysis and the measurement of PR and QRS interval of the 
ECG (QRS) intervals will be performed manually in 3 of the 10 ECG replicates at each 
timepoint. Each fiducial point (onset of P-wave, onset of Q-wave, offset of S-wave, and 
offset of T-wave) will be electronically marked. 
For T-wave morphology and U-wave presence, treatment-emergent changes will be assessed 
(ie, changes not present at baseline). For each category of T-wave morphology and U-waves, 
the category will be deemed as present if observed in any replicate at the timepoint. For 
baseline, the category will be deemed as present if observed in any replicate from all 
timepoints that constitute baseline. 
7.2.2. 
Safety 12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at 
least 5 minutes at the times indicated in the Schedule of Assessments in Appendix 6. Single 
12-lead ECGs will be repeated twice, and an average taken of the 3 readings, if either of the 
following criteria applies: 
• QT interval corrected for HR using Fridericia’s method (QTcF) is >500 ms 
• QTcF change from the baseline (predose) is >60 ms. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically 
appropriate or if the ongoing review of the data suggests a more detailed assessment of ECGs 
is required. The investigator (or designee) will perform a clinical assessment of each 12-lead 
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7.2.3. 
Cardiac Telemetry Monitoring 
Subjects will be monitored via cardiac telemetry from approximately 1 hour prior to dose 
administration and until approximately 12 hours postdose on Days 1, 2, 3, and 7 (up-titration 
days; as described in Appendix 6). Based on the emerging safety data from the study, the 
duration of the telemetry may be extended if necessary. 
The start and stop date and time of the telemetry monitoring will be recorded in the eCRFs. 
Clinically significant abnormalities noted from telemetry monitoring will be confirmed by 
12-lead ECG if necessary, then after confirming, the abnormities will be reported as AEs in 
the eCRF. 
7.3. 
Pharmacokinetic Assessments  
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples (approximately 1 × 3 mL for CBP-307 and moxifloxacin assays) will be 
collected by venipuncture or cannulation at the times indicated in the Schedule of 
Assessments in Appendix 6. Procedures for collection, processing, and shipping of PK blood 
samples will be detailed in a separate document.  
7.3.2. 
Analytical Methodology 
Plasma concentrations of CBP-307 and moxifloxacin will be determined using a validated 
analytical procedure. Specifics of the analytical method will be provided in a separate 
document.  
7.4. 
Safety and Tolerability Assessments 
7.4.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF until the 
follow-up visit. Subjects will be observed for any signs or symptoms and asked about their 
condition by open questioning, such as “How have you been feeling since you were last 
asked?”, at least once each day while resident at the study site and each study visit. Subjects 
will also be encouraged to spontaneously report AEs occurring at any other time during the 
study. 
All nonserious AEs, whether reported by the subject voluntarily or upon questioning, or 
noted on physical examination, will be recorded from initiation of placebo administration to 
all subjects (Day -1) until study completion. If AEs that occur in the screening prior to 
placebo administration to all subjects (Day -1) are considered to be related to the study 
procedure, they should be also collected. Serious AEs will be recorded from the time the 
subject signs the ICF until study completion. The nature, time of onset, duration, and severity 
will be documented, together with an investigator’s (or designee’s) opinion of the 
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Adverse events recorded during the course of the study will be followed up, where possible, 
to resolution or until the unresolved AEs are judged by the investigator (or designee) to have 
stabilized. This will be completed at the investigator’s (or designee’s) discretion. 
7.4.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations at the times 
indicated in the Schedule of Assessments in Appendix 6. Clinical laboratory evaluations are 
listed in Appendix 2. 
A serum qualitative pregnancy or urine test (females only) and follicle-stimulating hormone 
test (postmenopausal females only) will be performed at the timepoints specified in 
Appendix 6. A positive urine pregnancy test will be confirmed with a serum pregnancy test. 
All pregnancies should be reported as specified in Appendix 1. 
Additional clinical laboratory evaluations will be performed at other times if judged to be 
clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of clinical laboratory safety evaluations is required. At the discretion of the 
investigator, clinically significant clinical laboratory assessments may be confirmed by repeat 
sampling. If the clinical significance is confirmed, subjects will be excluded from 
participation or, if already included, will be followed until normalization of the test result or 
for as long as the investigator considers necessary. 
Subjects will be asked to provide urine samples for drugs of abuse screen and cotinine test, 
and will undergo an alcohol breath test at the times indicated in the Schedule of Assessments 
in Appendix 6. For all female subjects, a pregnancy test will be performed at the times 
indicated in the Schedule of Assessments in Appendix 6.   
An investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.4.3. 
Vital Signs 
Supine blood pressure, supine pulse rate, respiratory rate, and tympanic temperature will be 
assessed at the times indicated in the Schedule of Assessments in Appendix 6. Vital signs 
may also be performed at other times if judged to be clinically appropriate or if the ongoing 
review of the data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly. For all subjects, the screening, check-in, or 
baseline blood pressure, pulse rate, and respiratory rate may be repeated after 5 to 10 minutes 
if the initial reading is believed to be atypical for the subject. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
7.4.4. 
Physical Examination 
A full physical examination will be performed at the timepoints specified in the Schedule of 
Assessments in Appendix 6. Physical examinations include general appearance, head, eyes, 


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ears, nose, and throat, neck (including thyroid and nodes), cardiovascular, respiratory, 
gastrointestinal, renal, neurological, musculoskeletal, skin, and others. 
Height, weight, and body mass index will be assessed at screening. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Sample Size for Primary Analysis: 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-msec QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-307 
in the study. This power is estimated approximately using a 2-sample t-test. The calculation 
assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 3 msec and a 
standard deviation (SD) of the ΔQTcF of 8 msec for both CBP-307 and placebo treatment 
groups. Note that this calculation is conservative, since it does not take into account any gain 
in precision due to the use of all data of each subject with the help of a linear mixed-effects 
model. The concentration-QTc analysis method is supported by Darpo et al 20153 and 
Ferber et al, 2015,4 and consistent with the experiences from 25 recent TQT studies. 
Sample Size Considerations for Assay Sensitivity: 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that the 
ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 msec (ie, the lower bound of the 
2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 msec). In a similarly 
designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the standard 
error (SE) for the prediction of the QT effect of moxifloxacin based on the exposure-response 
analysis was 1.24 msec. The within-subject SD of ΔQTcF in the referred study was 5.4 msec 
based on the by-timepoint analysis. If the effect of moxifloxacin is assumed to be 10 msec, 
the SE of 1.24 msec corresponds to an effect size of (10-5)/(1.24×sqrt[24])=0.82, where the 
effect size is the effect assumed under the alternative hypothesis divided by the SD of the test 
variable. This value should be compared to the effect size of 0.64 required to guarantee a 
power of at least 95% in a paired t-test situation with a sample size of 28 evaluable subjects. 
In other words, based on this calculation, a power of at least 95% will be obtained as long as 
the variability of the ΔQTcF, as measured by its within-subject SD from the by-timepoint 
analysis, does not exceed 6.9 msec (ie, 128% [= 0.82/0.64] of the 5.4 msec observed in the 
referred study assuming the ratio of effective sizes is consistent with inverse ratio of 
within-subject SD). The number also agrees with recent recommendations of the FDA, which 
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8.2. 
Analysis Populations 
8.2.1. 
Cardiodynamic Population 
The QT/QTc population will include all subjects in the safety population with measurements 
at baseline as well as on-treatment with at least 1 postdose timepoint with a valid ΔQTcF 
value. The QT/QTc population will be used for the by-timepoint and categorical analyses of 
the cardiodynamic ECG parameters. 
The PK/QTc population will include all subjects who are in both the QT/QTc and PK 
populations with at least 1 pair of postdose PK and ∆QTcF data from the same timepoint as 
well as subjects in the QT/QTc population who received placebo. The PK/QTc population 
will be used for the concentration-QTc analysis and assay sensitivity. PK/QTc population 
will be defined for CBP-307, and for moxifloxacin.  
The as-treated principle will be applied to all analysis populations mentioned below. 
8.2.2. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of investigational 
product and have evaluable PK data of any of the analytes (CBP-307 and moxifloxacin). A 
subject will be excluded from the PK summary statistics and statistical analysis if the subject 
has an AE of vomiting that occurs at or before 2 times median time to maximum 
concentration.  
8.2.3. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of investigational 
product drug (therapeutic and supratherapeutic doses of CBP-307, moxifloxacin, or placebo). 
8.3. 
Cardiodynamic ECG Analyses 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus 
placebo in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1, baseline will be Day 16, on 
which subjects are administered placebo. For placebo-correction in this group, 
placebo values will be derived from Day 15 on which subjects are administered 
placebo, and baseline will be obtained on Day -1. 
• Group 2B: For moxifloxacin administered on Day 16, baseline will be Day 1, on 
which subjects are administered placebo. For the placebo-correction in this group, 
Day -1 values will be used as placebo (no treatment) and baseline will be obtained on 
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Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as 
the dependent variable, time-matched concentrations of CBP-307 as the exploratory variate 
(0 for placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on 
Days 1, 6, and 15 categorical) as fixed effects, and a random intercept and slope per subject.6  
The degrees of freedom estimates will be determined by the Kenward-Roger method. From 
the model, the slope (ie, the regression parameter for the CBP-307 concentration) and the 
treatment effect-specific intercept will be estimated together with 2-sided 90% CI. The 
estimates for the time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-time point analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 6, 
and 15, and Days 1 and 16 for active versus placebo and moxifloxacin versus placebo, 
respectively. All times are relative to the time of dosing on that day which is considered the 
first dose for the assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the 
first dose of study treatment is on Day 1. 
The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in 
the active drug groups on each of Days 6 and 15 will be determined, respectively. The 
predicted effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF 
(ΔΔQTcF) (ie, slope estimate × concentration + treatment effect-specific intercept) at this 
geometric mean Cmax will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the 
observed ΔQTcF values adjusted by population time effect estimated from the model will be 
used. These individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed 
individual ΔQTcFi,k for subject i administered with active drug or placebo at timepoint k 
minus the estimated population mean placebo effect at timepoint k (ie, time effect). A decile 
plot, ie, plot of the deciles of observed concentrations and the mean placebo-adjusted ΔQTcF 
(ΔΔQTcF) and 90% CI at the median concentration within each decile will be given. The 
regression line presenting the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a 
linear model and visualize the concentration-response relationship. The placebo-adjusted 
ΔQTcFi,j equals the individual ΔQTcFi,j for subject i administered with CBP-307 at timepoint 
j minus the estimation of time at timepoint j (ie, time effect). Additional exploratory analyses 
(via graphical displays and/or model fitting) will include accounting for a delayed effect 
(hysteresis) and the justification for the choice of PD model (linear versus nonlinear) as 
follows. 
Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the 
observed geometric mean Cmax on Days 6 and 15 as well as clinically relevant plasma levels 
is below 10 msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax 


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<10 msec), it can be concluded that CBP-307 does not cause clinically concerning QT 
prolongation within the observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 6 and 15; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on 
Days 6 and 15; and if the difference (delay) between the time to reach the peak QTc effect 
(ΔΔQTcF) and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of 
more than 1 hour is observed in a consistent way for the active dose groups on Days 6 and 15, 
other concentration-QTc models, such as a model with an effect compartment, may be 
explored. With the provision stated above, hysteresis will be assumed if this curve shows a 
counterclockwise loop. A significant treatment effect-specific intercept may also be 
indicative of hysteresis or model misspecification, if it cannot be explained by a nonlinear 
relationship. 
Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 
time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a 
scatter plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI 
and a linear regression line will also be provided to check the assumption of a linear 
concentration-QTc relationship. If there is an indication that a linear model is inappropriate, 
additional models may be fitted, such as an E-max model. The concentration-QTc analysis 
will then be repeated for the model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of 
moxifloxacin data. If the slope of the concentration-QTc (change-from-baseline QTcF) for 
moxifloxacin is statistically significant at 10% level for 2-sided test and the lower bound of 
the 2-sided 90% CI of the predicted effect is above 5 msec at the observed geometric mean 
Cmax of the 400-mg dose, assay sensitivity will be deemed to have been demonstrated. 
By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 


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time-by-treatment interaction as fixed effects. An unstructured covariance matrix will be 
specified for the repeated measures at postdose timepoints within subjects. If the model with 
unstructured covariance matrix fails to converge, other covariance matrices such as 
compound symmetry and autoregressive will be considered. From this analysis, the LS mean, 
SE, and 2-sided 90% CIs will be calculated for the contrast “CBP-307 versus placebo” for 
each day of Days 1, 6, and 15 at each postbaseline timepoint on Days 1, 6, and Day 15, 
respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo 
at postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used 
with ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 
16: categorical), treatment (moxifloxacin and placebo), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. An unstructured 
covariance matrix will be specified for the repeated measures at postbaseline timepoints for 
subject within visit. The model will also include a subject-specific random effect. If the 
model with an unstructured covariance matrix fails to converge, other covariance matrices, 
such as compound symmetry or autoregressive, will be considered. From this analysis, the LS 
mean, SE, and 2-sided 90% CIs will be calculated for the contrast “moxifloxacin versus 
placebo” at each postbaseline timepoint, respectively. 
For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline 
postdose (ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as 
described for QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both 
change-from-baseline and placebo-corrected change-from-baseline values will be listed in the 
tables and graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will 
be summarized in frequency tables with counts (percentages) for both the number of subjects 
and the number of timepoints. For categorical outliers, the number (percentage) of subjects as 
well as timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 
and ≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline 
>25% to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR 
>100 bpm will be determined. For T-wave morphology and U-wave presence, the analyses 
will be focused on change from baseline (ie, treatment-emergent changes). 
8.4. 
Pharmacokinetic Analyses 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, SD, median, minimum, 
maximum geometric mean, and geometric coefficient of variation) separately by group. 
Individual and mean plasma CBP-307 and moxifloxacin concentration versus time data will 
be tabulated and plotted by dose level. Graphical displays of PK data may be provided as 
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For each subject, the following PK parameters will be calculated, whenever possible, based 
on the plasma concentration for CBP-307 and moxifloxacin, according to the model 
independent approach: 
• Cmax 
• tmax 
• AUC0-24  
• AUCinf 
• apparent terminal elimination rate constant (λZ) 
• t1/2  
• apparent total clearance (CL/F) 
• apparent volume of distribution during the terminal phase (Vz/F)  
• Accumulation ratio (Rac) for Cmax (Rac[Cmax]) and Rac(AUC0-24), calculated as Day 15 
Cmax/Day 7 Cmax and Day 15 AUC0-24/Day 7 AUC0-24, respectively. 
Pharmacokinetic calculations will be performed, if appropriate, using commercial software 
such as Phoenix® WinNonlin® (Version 8.1 or higher). 
Other parameters may be added as appropriate. 
Pharmacokinetic analysis will use actual times as recorded on the eCRF. Other data handling 
procedures will be detailed in the Statistical Analysis Plan. 
8.5. 
Safety Analysis 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed.   
8.6. 
Interim Analysis 
No interim analyses are planned for this study.  
9. REFERENCES 
1. Suzhou Connect. CBP-307 – Investigator’s Brochure. (Version 6.0). December 2020. 
2. Avelox [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016. 


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3. Darpo B, Benson C, Dota C, et al. Results from the IQ-CSRC prospective study support 
replacement of the thorough QT study by QT assessment in the early clinical phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
4. Ferber G, M Zhou, B Darpo. Detection of QTc effects in small studies--implications for 
replacing the thorough QT study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
5. Huang DP, Chen J, Dang Q, et al. Assay sensitivity in “Hybrid thorough QT/QTc (TQT)” 
study. Journal of Biopharmaceutical Statistics. 2019;29(2):378-384. 
6. Garnett C, Bonate PL, Dang Q , et al. Scientific white paper on concentration-QTc 
modeling. [Published correction appears in J Pharmacokinet Pharmacodyn. 
2018;45(3):399]. J Pharmacokinet Pharmacodyn. 2018;45(3):383-397. 
7. Tornøe CW, Garnett CE, Wang Y, et al. Creation of a knowledge management system for 
QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042. 
8. Cleveland WS. Robust Locally Weighted Regression and Smoothing Scatter Plots. 
J Amer Statist Assoc. 1979;74(368):829-36. 
9. Hurvich CM, Simonoff JS, Tsai CL. Smoothing parameter selection in nonparametric 
regression using an improved Akaike information criterion. J Roy Statist Soc Ser B Stat 
Methodol. 1998;60(2):27-193. 
 
 


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10. APPENDICES 


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Appendix 1: Adverse Event Reporting 
Definitions 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a study treatment, whether or not related to the study 
treatment. This includes any newly occurring event or previous condition that had increased 
in severity or frequency since the administration of study medication.  
Examples of AEs include: 
• Symptoms described by the subject, or signs observed by the investigator, and 
• Abnormal findings (involving clinically significant abnormal laboratory tests, ECG, 
etc.)  
• Exacerbation of previous condition, including increased incidence and/or severity. 
Note: Regarding decreased lymphocyte count in peripheral blood in this study, please report 
them as follows: 
• Since a decreased lymphocyte count in peripheral blood is due to the mechanism of 
action of the drug, it is not to be reported as an AE. However, clinical diagnosis 
related to a decreased lymphocyte count in peripheral blood indicates AE reporting (if 
no diagnosis is available, it is required to report related clinical symptoms or signs). 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs. All AEs will 
be recorded in the medical records and eCRFs. The investigator (or designee) is to record in 
detail any AE that occurred to the subject, including: AE diagnosis whenever possible, or 
signs, symptoms, the start date and time of occurrence, the stop date and time of occurrence, 
seriousness (ie, whether it is an SAE), severity of AEs, causality assessment, actions taken on 
the investigational product, other actions (eg, medications/treatments given), and outcomes of 
AEs.  
Assessment of Severity 
The investigator will be asked to provide an assessment of the severity of the AE using the 
following categories:  
• Mild: Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily 
living. 
• Moderate: Usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 


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• Severe: Interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
Relationship to Study Treatment 
The investigator (or designee) will make a determination of the relationship of the AE to the 
study treatment using a 4-category system according to the following guidelines: 
• Not Related: The AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions. 
• Unlikely Related: The temporal association between the AE and the drug is such that 
the drug is not likely to have any reasonable association with the AE. 
• Possibly Related: The AE follows a reasonable temporal sequence from the time of 
drug administration but could have been produced by the subject’s clinical state or the 
study procedures/conditions. 
• Related: The AE follows a reasonable temporal sequence from the administration of 
the drug, abates upon discontinuation of the drug, follows a known or hypothesized 
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced.  
Follow-up of Adverse Events 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject 
who has an ongoing AE that is possibly related or related to the IMP or study procedures at 
the follow-up visit will be followed up, where possible, until resolution or until the 
unresolved AE is judged by the investigator (or designee) to have stabilized. This will be 
completed at the investigator’s (or designee’s) discretion. Any subject who has an ongoing 
AE that is not related or unlikely related to the IMP or study procedures at the follow-up visit 
can be closed out as ongoing at the investigator’s discretion.  
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
For marketed medicinal products, a response to a drug that is noxious and unintended and 
which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases 
or modification of physiological function is to be considered an adverse drug reaction. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, IB for an unapproved 
IMP). 
Serious Adverse Events 
All SAEs will be collected after subjects sign the informed consent form and throughout the 
entire study, ie, until the end-of-study as specified in the protocol (or at early termination). 


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An SAE is defined as any untoward medical occurrence that at any dose either: 
• results in death 
• is life-threatening 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
• results in a congenital anomaly/birth defect 
• results in an important medical event (see below). 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Instances of death or congenital abnormality, if brought to the attention of the investigator at 
any time after cessation of the study treatment and considered by the investigator to be 
possibly related to the study treatment, will be reported to the sponsor (or designee). 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalization 
Adverse events requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the subject has been detained (usually involving an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate at the study site. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered as serious. 
Hospitalization for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a clinical assessment form and 
added to the eCRF. If anything untoward is reported during the procedure, this must be 
reported as an AE and either ‘serious’ or ‘nonserious’ attributed according to the usual 
criteria. 
Serious Adverse Event Reporting 
The investigator will complete an SAE report form and forward it by facsimile or email to 
Labcorp APAC Drug Safety and the sponsor immediately (within 24 hours) upon becoming 
aware of an SAE. 


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All SAEs must be reported immediately (within 24 hours of discovery) to: +61-2-8879-2000 
SAE Reporting email: SAEIntake@labcorp.com (preferred method) 
Labcorp Safety SAE Reporting Fax Number: 61-2-6100-9788 or 1800-882-203 (toll free) 
The responsibilities of Labcorp APAC Drug Safety include the following: 
• Prepare an AE reporting plan prior to the start of the study. Where this plan differs 
from the applicable study site standard operating procedure on SAE reporting, the 
safety management plan will always take precedence. 
• Receive and review SAE report forms from the study site and inform the sponsor of 
the SAE within 1 working day of the initial notification to Labcorp APAC Drug 
Safety who will delete any information from the SAE report forms that may identify 
the subject. 
• Write case narratives and enter the case into Labcorp’s safety database as defined in 
the AE reporting plan. 
• Produce appropriate reports of all suspected unexpected serious adverse reactions and 
forward them to the EC, Medicines and Healthcare Products Regulatory Agency, 
principal investigator, and the sponsor within the timeframes stipulated in the Clinical 
Trials Directive Guideline (ENTR/CT 3).  
The responsibility for reporting SAEs will be transferred to the sponsor 28 days after the end 
of the study. 
For SAEs, the active reporting period to sponsor or its designated representative begins from 
the time that the subject provides informed consent through to the last subject visit.  
Nonserious AEs should be collected from the time the subject has taken the placebo dose on 
Day -1 through the last subject visit. If AEs that occur in the screening prior to the placebo 
administration to all subjects on Day -1 are considered to be related to the study procedure, 
they should be also collected.  
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, the 
sponsor should be notified within 24 hours of investigator awareness of the event. This time 
frame also applies to additional new information (follow-up) on previously forwarded SAE 
reports as well as to the initial and follow-up reporting of exposure during pregnancy.  
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.  
For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the time frames for reporting as specified above. In addition, an investigator 


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may be requested by the sponsor to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured on 
the AE eCRF. In general, this will include a description of the AE in sufficient detail to allow 
for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to the sponsor 
or its designated representative. 
Pregnancy 
Pregnancy (maternal or paternal exposure to study treatment) does not meet the definition of 
an AE. However, to fulfill regulatory requirements any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus. 
If the female subject becomes pregnant during the clinical trial and has not yet been dosed 
with study treatment, she must be withdrawn from the study. If the female subject becomes 
pregnant during the clinical trial and has been dosed, she must discontinue treatment 
immediately but may remain on study for safety evaluations. If the partner of a male subject 
becomes pregnant during the clinical trial, the subject can continue the clinical trial.  
For pregnancy of female subjects or partners of the male subjects during this study, 
investigators should report to the sponsor or designee in a pregnancy report form within 
24 hours after investigator awareness and report to the EC in time as per local requirement.  
The investigator will follow up on pregnancy outcomes, until not less than 12 months after 
birth, unless otherwise justified, and will report the outcome to the sponsor and ethics 
committee.  
If any adverse pregnancy outcome (eg, the outcome of the pregnancy is stillbirth, 
spontaneous abortion, or fetal malformations), it should be considered as an SAE and be 
reported in accordance with SAE reporting requirements. 
 
 


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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate  
Magnesium 
Potassium  
Sodium  
Total bilirubin 
Total protein 
Urea 
Uric acid 
Hematocrit  
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell count 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
 
Blood 
Glucose 
Ketones 
Leukocyte esterase  
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination  (if 
indicated by dipstick) 
Serology: 
Drug screen: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency (HIV-1 
and HIV-2) antibodies and p24 
antigen 
Syphilis 
Including but not limited to:  
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol 
Tricyclic antidepressants 
Cotinine test 
Follicle-stimulating hormone 
(postmenopausal females only) 
Serum pregnancy test (human 
chorionic gonadotropin)b 
Urine pregnancy testb  
Other Tests 
Low density lipoprotein cholesterol 
High-density lipoprotein 
cholesterol 
Triglycerides 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated.  
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the 
follow-up visit (on Day 29±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  


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Appendix 3: Total Blood Volume 
The following blood volumes will be withdrawn for each subject. 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
41 
328 
Total: 
390.5 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed 500 mL. 


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Appendix 4: Contraception Guidance 
Definitions 
Women of Childbearing Potential: premenopausal females who are anatomically and 
physiologically capable of becoming pregnant following menarche. 
Women of Nonchildbearing Potential:  
1. Surgically sterile: females who are permanently sterile via hysterectomy, 
bilateral salpingectomy, and/or bilateral oophorectomy by reported medical 
history and/or medical records. Surgical sterilization to have occurred a minimum 
of 6 weeks, or at the investigator’s discretion, prior to screening. 
2. Postmenopausal: females at least 45 years of age with amenorrhea for 12 months 
without an alternative medical reason with confirmatory follicle-stimulating 
hormone (FSH) levels of ≥40 mIU/mL. The amenorrhea should not be induced by 
a medical condition such as anorexia nervosa, hypothyroid disease or polycystic 
ovarian disease, or by extreme exercise. It should not be due to concomitant 
medications that may have induced the amenorrhea such as oral contraceptives, 
hormones, gonadotropin-releasing hormones, anti-estrogens, or selective estrogen 
receptor modulators. Females on hormone replacement therapy with FSH levels 
<40 mIU/mL may be included at the discretion of the investigator.   
Fertile male: a male that is considered fertile after puberty. 
Infertile male: permanently sterile male via bilateral orchiectomy. 
Contraception Guidance 
Female Subjects 
Female subjects who are of nonchildbearing potential will not be required to use 
contraception. Female subjects of childbearing potential must be willing to use 2 methods 
(1 primary and 1 secondary method) of birth control from the time of signing the ICF until 
90 days after the follow-up visit. Primary (non-barrier) methods of contraception include: 
• surgical method performed at least 3 months prior to the screening visit: 
o 
bilateral tubal ligation or bilateral salpingectomy 
o 
Essure® (hysteroscopic bilateral tubal occlusion) with confirmation of 
occlusion of the fallopian tubes 
• non-hormonal intrauterine device or Mirena® (other hormonal intrauterine devices 
will not be allowed) in place for at least 3 months prior to the first dose of the study 
drug 
• vasectomized male partner (sterilization performed at least 90 days prior to the 
screening visit, with verbal confirmation of surgical success, and the sole partner for 
the female subject)  


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Secondary (barrier) methods of contraception include: 
• male condom without spermicide 
• female condom without spermicide 
• cervical cap without spermicide (as prescribed) 
• diaphragm without spermicide (as prescribed). 
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2) until 90 days after the follow-up visit. 
Male Subjects 
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (ie, male condom without spermicide) in addition 
to a second method of acceptable contraception from check-in until 90 days after the 
follow-up visit. Acceptable methods of contraception for female partners include: 
• hormonal injection 
• combined oral contraceptive pill or progestin/progestogen-only pill 
• combined hormonal patch 
• combined hormonal vaginal ring 
• surgical method (bilateral tubal ligation or Essure® [hysteroscopic bilateral tubal 
occlusion])  
• hormonal implant 
• hormonal or non-hormonal intrauterine device 
• cervical cap without spermicide 
• diaphragm without spermicide. 
An acceptable second method of contraception for male subjects is vasectomy that has been 
performed at least 90 days prior to the screening visit with verbal confirmation of surgical 
success. 
For male subjects (even with a history of vasectomy), sexual intercourse with female partners 
who are pregnant or breastfeeding should be avoided unless condoms are used from the time 
of the first dose until 90 days after the follow-up visit. Male subjects are required to refrain 
from donation of sperm from check-in until 90 days after the follow-up visit. 
Sexual Abstinence and Same-sex Relationships 
Subjects who practice true abstinence, because of the subject’s lifestyle choice (ie, the subject 
should not become abstinent just for the purpose of study participation), are exempt from 
contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, symptothermal, 
postovulation methods) and withdrawal are not acceptable methods of contraception. If a 


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subject who is abstinent at the time of signing the ICF becomes sexually active they must 
agree to use contraception as described previously.  
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. If a subject who is in a same-sex relationship at the time of signing the ICF becomes 
engaged in a heterosexual relationship, they must agree to use contraception as described 
previously. 


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Appendix 5: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol, local legal and regulatory 
requirements and with the following: 
• General principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), Guidelines for good clinical practice (GCP) (ICH 1996), and 
the Declaration of Helsinki (World Medical Association 2008).  
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents must be 
submitted to the human research ethics committee (HREC) by the investigator and reviewed 
and approved by the HREC before the study is initiated.  
Any protocol amendments will require EC approval before implementation of changes made 
to the study design, except for changes necessary to eliminate an immediate hazard to study 
subjects.  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents from the 
HREC. All correspondence with HREC should be retained in the investigator file. A copy of 
HREC approval should be forwarded to the sponsor. 
• The investigator will be responsible for the following:  
• Providing written summaries of the status of the study to the EC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the EC.  
• Notifying the EC of SAEs or other significant safety findings as required by EC 
procedures.  
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of ICH guidelines, the EC, and all other applicable local regulations.  
Regulatory Authority  
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency 
in accordance with any applicable country-specific regulatory requirements before the study 
is initiated at a study center in that country. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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Informed Consent 
Prior to starting participation in the study, each subject will be provided with a study-specific 
ICF giving details of the study treatments, procedures, and potential risks of the study. 
Subjects will be instructed that they are free to obtain further information from the 
investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. Subjects will be given an opportunity to ask questions 
about the study prior to providing consent for participation. 
Following the discussion of the study with study site personnel, subjects will sign the ICF in 
the presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. A copy of the ICF will be given to the subject. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
Subject Data Protection 
Subjects will be assigned a unique identifier and will not be identified by name in eCRFs, 
study-related forms, study reports, or any related publications. Subject and investigator 
personal data will be treated in compliance with all applicable laws and regulations. In the 
event the study protocol, study report, or study data are included in a public registry, all 
identifiable information from individual subjects or investigators will be redacted according 
to applicable laws and regulations.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. The subject must also be informed that his/her study-related data 
may be examined by sponsor or contract research organization (CRO) auditors or other 
authorized personnel appointed by the sponsor, by appropriate EC members, and by 
inspectors from regulatory authorities. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the sponsor. 
Data Quality Assurance 
The following data quality steps will be implemented: 
• All relevant subject data relating to the study will be recorded on eCRFs unless 
directly transmitted to the sponsor or designee electronically (eg, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRF.  


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• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
• The investigator must permit study-related monitoring, audits, EC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Predefined agreed risks, monitoring thresholds, 
quality tolerance thresholds, controls, and mitigation plans will be documented in a 
risk management register. Additional details of quality checking to be performed on 
the data may be included in a data management plan.  
• A study monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator in the study site archive for at least 5 years after 
the end of the study unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 Code of Federal 
Regulations Part 11-compliant electronic data capture (EDC) system on an eCRF in a timely 
fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and 
transmitted to the sponsor or designee electronically, will be integrated with the subject’s 
eCRF data in accordance with the data management plan.  
An eCRF must be completed for each enrolled subject who undergoes any screening 
procedures, according to the eCRF completion instructions. The sponsor, or CRO, will 
review the supporting source documentation against the data entered into the eCRFs to verify 
the accuracy of the electronic data. The investigator will ensure that corrections are made to 
the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The investigator will sign and date the eCRF via the EDC system’s electronic signature 
procedure. These signatures will indicate that the investigator reviewed and approved the data 
on the eCRF, data queries, and site notifications. 


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Publications 
Publications will be addressed as follows:The results of this study may be published or 
presented at scientific meetings. If this is foreseen, the investigator agrees to submit all 
manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect 
proprietary information and provide comments. 
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support the publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 


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Appendix 6: Schedule of Assessments 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinical 
research unit1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from clinical 
research unit2  
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height/weight/BMI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematology 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Clinical chemistry  
(including cholesterol panel 
tests) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, or 
HCVAb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead safety 
electrocardiogram4,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Cardiac Telemetry 
Monitoring9 
 
 
 
X 
X 
X 
(Day 3) 
 
X 
 (Day 7) 
 
 
 
 
 
 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
 
 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Follicle -stimulating 
hormone test 
(postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBP-307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Moxifloxacin/placebo 
administration 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).  
2. Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19. 
3. Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 18, and 19): 
Prior to and 2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: Tympanic temperature, 
respiratory rate, and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to discharge, supine vital signs (tympanic 
temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): Tympanic temperature, respiratory rate, and supine pulse 
rate and blood pressure. 


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4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before discharge on 
Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before 
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1, 
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. The ECG effects 
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 (supratherapeutic 
concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 16. 
6. Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 29±2 days). A positive urine 
pregnancy test will be confirmed with a serum pregnancy test. 
7. Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16). 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 hour postdose, ±15 minutes for ECGs and vital 
sign measurements at 2 hours postdose and ±5 minutes for PK sampling at 2 hours postdose, ±5 minutes for 3 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, 
and ±30 minutes for 12 to 24, 72, and 96 hours postdose. 
9. Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 12 hours 
postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended if necessary. The 
start and stop date and time of the telemetry monitoring will be recorded in the eCRF. 


Protocol Amendment 1 
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Protocol Version 2.0, 10 May 2021  
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Summary of Amended Protocol Changes 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Protocol Amendment 1 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment 1 Date: 10 May 2021 
Investigational Medicinal Product: CBP-307 
 
Protocol Reference Number: CBP-307AU002 
Covance Study Number: 8463245 
IND Number: 134585 
 
 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Site: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Sponsor Signatory: 
Ping Li, MD 
 
Principal Investigator: 
Nicholas Farinola, MBBS 
 
 
 
Information described herein is confidential and may be disclosed only with the express 
written permission of the Sponsor. 
________________________________________ 


Protocol Amendment 1 
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Protocol Version 2.0, 10 May 2021  
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The primary changes in this amendment, along with the rationale for the/each change as 
appropriate, are: 
1. Update the protocol to add a new CBP-307 dose group (0.05 mg) in the up-titration 
period. 
2. Update the applicable assessment timepoints throughout the protocol to align with the 
additional dose group added in the up-titration period. 
3. Update the protocol to include additional pharmacokinetic (PK) sample collections at 
72 and 96 hours after the final CBP-307 dose on Day 15 to better capture the terminal 
phase PK parameters of CBP-307 after 0.5 mg multiple doses. 
4. Update the protocol to include additional PK parameters. 
5. Update the protocol to include cardiac telemetry monitoring. 
Minor changes: 
1. Minor editorial changes have been made. 
2. The protocol version and date were updated throughout the protocol. 
3. Typographical errors and formatting errors were corrected, as necessary. 
A detailed summary of changes is presented below: 
Synopsis, Study Design 
Previously read: 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-
controlled, single-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic 
oral doses of CBP-307 on the QTc interval in healthy male and female subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After informed 
consent is obtained, screening procedures and tests to establish subject eligibility to enter the 
study will be performed within 28 days before Day 1. After informed consent has been obtained 
but prior to the initiation of study treatment administration, only serious adverse events (SAEs) 
will be reported. After placebo administration to all subjects on Day -1, all adverse events (AEs), 
whether volunteered, elicited, or noted upon physical examination, will be recorded throughout 
the study (ie, from Day -1 until the end of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be randomized 
into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. Randomized 
subjects will receive the assigned study drug as a single dose in the morning on Days 1, 2 to 5, 6 
to 14, and on Day 15 (placebo will be administered to all subjects on Day -1).  


Protocol Amendment 1 
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Protocol Version 2.0, 10 May 2021  
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The following treatments will be administered: 
 A starting dose of CBP-307 for titration (0.1 mg, Day 1) 
 A therapeutic dose of CBP-307 (0.2 mg, Day 2 to 5) 
 A supratherapeutic dose of CBP-307 (0.5 mg, Day 6 to 14) 
 Placebo (matched to moxifloxacin and CBP-307) 
 Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) of 
10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 and 
will remain at the study site until discharge on Day 16. Treatment administration will occur on 
Days 1, 2 to 5, 6 to 14, and 15 under fasting conditions (all subjects will receive placebo on 
Day -1). Continuous cardiodynamic electrocardiogram (ECG) monitoring and recording will 
begin at least 25 hours prior to the administration of study treatments on Day 1 and continue 
through 24 hours after the administration of study treatments on Days 1, 5, 14, and 15 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK analysis 
will be collected predose and at each postdose cardiodynamic ECG timepoint. Subjects will 
return to the study site for a follow-up visit on Day 28±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 5, 14, and 15. 
The recording will be started 1 hour before dosing and at the corresponding clock time on Day -
1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-
30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. Pharmacokinetic 
blood samples will be collected at the following timepoints: prior to dosing and 0.5, 1, 2, 3, 4, 6, 
8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 5, 14, and 15; sample 
collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 
hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 12 to 24 hours 
postdose). Subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 
minutes after each cardiodynamic ECG extraction timepoint, which will end immediately prior 
to the PK sampling. When timepoints for ECG extraction, safety ECGs, vital sign measurements, 
and blood draws coincide, procedures will be performed in said order. At each timepoint, up to 
10 ECG replicates will be extracted from a 5-minute time window (the last 5 minutes of the 15-
minute period when the subject is maintained in a supine, quiet position). The ECG effects of 
CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 5 (therapeutic 
concentrations versus placebo), and Day 14 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be evaluated using ECG data collected on Days -1, 1, 
14, and 15. 


Protocol Amendment 1 
CONFIDENTIAL 
Covance Study: 8463245 
Protocol Reference: CBP-307AU002 
 
Protocol Version 2.0, 10 May 2021  
Page 4 of 31 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and sent to 
the central ECG laboratory for review. Resting ECGs to be used in the analyses will be selected 
from predetermined timepoints specified above and will be read by the central ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, and 
physical examination findings will be performed at screening and at specific timepoints during 
the study, and/or at the follow-up visit.  
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 58 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of enrollment 
occurs at the time of subject number allocation. The end of the study is defined as the date of the 
last subject’s last assessment (scheduled or unscheduled). 
Now reads: 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-
controlled, single-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic 
oral doses of CBP-307 on the QTc interval in healthy male and female subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After informed 
consent is obtained, screening procedures and tests to establish subject eligibility to enter the 
study will be performed within 28 days before Day 1. After informed consent has been obtained 
but prior to the initiation of study treatment administration, only serious adverse events (SAEs) 
will be reported. After placebo administration to all subjects on Day -1, all adverse events (AEs), 
whether volunteered, elicited, or noted upon physical examination, will be recorded throughout 
the study (ie, from Day -1 until the end of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be randomized 
into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. Randomized 
subjects will receive the assigned study drug as a single dose in the morning on Days 1, 2, 3 to 6, 
7 to 15, and on Day 16 (placebo will be administered to all subjects on Day -1).  
The following treatments will be administered: 
 Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
 A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
 A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
 Placebo (matched to moxifloxacin and CBP-307) 


Protocol Amendment 1 
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 Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) of 
10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 and 
will remain at the study site until discharge on Day 19. Treatment administration will occur on 
Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive placebo on 
Day -1). Continuous cardiodynamic electrocardiogram (ECG) monitoring and recording will 
begin at least 25 hours prior to the administration of study treatments on Day 1 and continue 
through 24 hours after the administration of study treatments on Days 1, 6, 15, and 16 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK analysis 
will be collected predose and at each postdose cardiodynamic ECG timepoint. Additional PK 
samples will be collected at 72 and 96 hours following dosing on Day 15. Subjects will return to 
the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 16. 
The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. Pharmacokinetic 
blood samples will be collected at the following timepoints: prior to dosing and 0.5, 1, 2, 3, 4, 6, 
8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16; sample 
collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 
4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 12 to 24 hours 
postdose). Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15 (sample collection window: ±30 minutes). Subjects will be inactive and in a supine 
position for at least 10 minutes prior to and 5 minutes after each cardiodynamic ECG extraction 
timepoint, which will end immediately prior to the PK sampling. When timepoints for ECG 
extraction, safety ECGs, vital sign measurements, and blood draws coincide, procedures will be 
performed in said order. At each timepoint, up to 10 ECG replicates will be extracted from a 
5-minute time window (the last 5 minutes of the 15-minute period when the subject is 
maintained in a supine, quiet position). The ECG effects of CBP-307 will be tested on data from 
Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and sent to 
the central ECG laboratory for review. Resting ECGs to be used in the analyses will be selected 
from predetermined timepoints specified above and will be read by the central ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, and 
physical examination findings will be performed at screening and at specific timepoints during 


Protocol Amendment 1 
CONFIDENTIAL 
Covance Study: 8463245 
Protocol Reference: CBP-307AU002 
 
Protocol Version 2.0, 10 May 2021  
Page 6 of 31 
the study, and/or at the follow-up visit. In addition, subjects will be monitored via cardiac 
telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of enrollment 
occurs at the time of subject number allocation. The end of the study is defined as the date of the 
last subject’s last assessment (scheduled or unscheduled). 
Synopsis, Investigational Medicinal Products, Dose and Mode of Administration 
Previously read: 
The following treatments will be administered: 
 A starting dose of CBP-307 for titration (0.1 mg, Day 1; oral capsule) 
 A therapeutic dose of CBP-307 (0.2 mg, Day 2 to 5; oral capsule) 
 A supratherapeutic dose of CBP-307 (0.5 mg, Day 6 to 14; oral capsule) 
 Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 
 Moxifloxacin (400 mg; oral tablet). 
Now reads: 
The following treatments will be administered: 
 Starting doses of CBP-307 for titration (0.05 mg on Day 1 titrated to 0.1 mg on Day 2; 
oral capsule) 
 A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6; oral capsule) 
 A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15; oral capsule) 
 Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 
 Moxifloxacin (400 mg; oral tablet). 
Synopsis, Duration of Study Participation in the Study 
Previously read: 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3), 18 days for the in-house treatment 


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Protocol Reference: CBP-307AU002 
 
Protocol Version 2.0, 10 May 2021  
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period (Days -2 to 16), and 12 ±2 days for follow-up (Day 28±2 days), in total approximately 
58 days. 
Now reads: 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3), 21 days for the in-house treatment 
period (Days -2 to 19), and 10 ±2 days for follow-up (Day 29±2 days), in total approximately 
59 days. 
Section 3.1, Overall Study Design and Plan 
Previously read: 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-
controlled, single-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic 
oral doses of CBP-307 on the QTc interval in healthy male and female subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After informed 
consent is obtained, screening procedures and tests to establish subject eligibility to enter the 
study will be performed within 28 days before Day 1. After informed consent has been obtained 
but prior to the initiation of study treatment administration, only SAEs will be reported. After 
placebo administration to all subjects on Day -1, all AEs, whether volunteered, elicited, or noted 
upon physical examination, will be recorded throughout the study (ie, from Day -1 until the end 
of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be randomized 
into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. Randomized 
subjects will receive the assigned study drug as a single dose in the morning on Days 1, 2 to 5, 
6 to 14, and on Day 15 (placebo will be administered to all subjects on Day -1).  
The following treatments will be administered: 
 A starting dose of CBP-307 for titration (0.1 mg, Day 1) 
 A therapeutic dose of CBP-307 (0.2 mg, Days 2 to 5) 
 A supratherapeutic dose of CBP-307 (0.5 mg, Days 6 to 14) 
 Placebo (matched to moxifloxacin and CBP-307) 
 Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) of 
10 to 15 msec.  


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An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 32 subjects 
in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. Subjects 
will be randomized to receive a treatment sequence that includes 4 treatments (CBP-307 therapeutic dose, CBP-307 
supratherapeutic dose, moxifloxacin, or placebo [matched to CBP-307 or moxifloxacin]); assigned study treatments will be 
administered on Day 1, Days 2 to 5, Days 6 to 14, and Day 15. Dosing details are provided in Table 3. 
Blood samples for pharmacokinetic analysis will be collected predose and at each postdose cardiodynamic electrocardiogram 
timepoint.  
An end-of-study visit will occur on Day 28±2 days. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 and 
will remain at the study site until discharge on Day 16. Treatment administration will occur on 
Days 1, 2 to 5, 6 to 14, and 15 under fasting conditions (all subjects will receive placebo on 
Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at least 25 hours 
prior to the administration of study treatments on Day 1 and continue through 24 hours after the 
administration of study treatments on Days 1, 5, 14, and 15 and at corresponding timepoints on 
the day before dosing, ie, Day -1. Blood samples for PK analysis will be collected predose and at 
each postdose cardiodynamic ECG timepoint. Subjects will return to the study site for a 
follow-up visit on Day 28±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 5, 14, and 15. 
The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. Pharmacokinetic 
blood samples will be collected at the following timepoints: prior to dosing and 0.5, 1, 2, 3, 4, 6, 
8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 5, 14, and 15; sample 
collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 
hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 12 to 24 hours 
postdose). Subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 
minutes after each cardiodynamic ECG extraction timepoint, which will end immediately prior 
Day 16
(Clinic 
Discharge)
Final 
Visit
(Day 28±2 
days)
Days 2 
to 5
Day 1
Day ‐2
(Check‐in)
Inpatient Treatment Period
Day ‐28 
to ‐3
(Screening)
Days 6 
to 14
Day 15
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day ‐1


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Protocol Version 2.0, 10 May 2021  
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to the PK sampling. When timepoints for ECG extraction, safety ECGs, vital sign measurements, 
and blood draws coincide, procedures will be performed in said order. At each timepoint, up to 
10 ECG replicates will be extracted from a 5-minute time window (the last 5 minutes of the 15-
minute period when the subject is maintained in a supine, quiet position). The ECG effects of 
CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 5 (therapeutic 
concentrations versus placebo), and Day 14 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be evaluated using ECG data collected on Days -1, 1, 
14, and 15. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and sent to 
the central ECG laboratory for review. Resting ECGs to be used in the analyses will be selected 
from predetermined timepoints specified above and will be read by the central ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, and 
physical examination findings will be performed at screening and at specific timepoints during 
the study, and/or at the follow-up visit.  
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 58 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of enrollment 
occurs at the time of subject number allocation. The end of the study is defined as the date of the 
last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 
Now reads: 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-
controlled, single-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic 
oral doses of CBP-307 on the QTc interval in healthy male and female subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After informed 
consent is obtained, screening procedures and tests to establish subject eligibility to enter the 
study will be performed within 28 days before Day 1. After informed consent has been obtained 
but prior to the initiation of study treatment administration, only SAEs will be reported. After 
placebo administration to all subjects on Day -1, all AEs, whether volunteered, elicited, or noted 
upon physical examination, will be recorded throughout the study (ie, from Day -1 until the end 
of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be randomized 
into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups (Group 
2A and 2B) and each sub-group will be randomized with 16 subjects. Randomized subjects will 
receive the assigned study drug as a single dose in the morning on Days 1, 2, 3 to 6, 7 to 15, and 
on Day 16 (placebo will be administered to all subjects on Day -1).  


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The following treatments will be administered: 
 Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
 A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
 A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
 Placebo (matched to moxifloxacin and CBP-307) 
 Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) of 
10 to 15 msec.  
An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 32 subjects 
in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. Subjects 
will be randomized to receive a treatment sequence that includes 4 treatments (CBP-307 therapeutic dose, CBP-307 
supratherapeutic dose, moxifloxacin, or placebo [matched to CBP-307 or moxifloxacin]); assigned study treatments will be 
administered on Day 1, Day 2, Days 3 to 6, Days 7 to 15, and Day 16. Dosing details are provided in Table 3. Blood samples for 
pharmacokinetic analysis will be collected predose and at each postdose cardiodynamic electrocardiogram timepoint. Additional 
PK samples will be collected at 72 and 96 hours following dosing on Day 15. An end-of-study visit will occur on Day 29±2 days. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 and 
will remain at the study site until discharge on Day 19. Treatment administration will occur on 
Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive placebo on 
Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at least 25 hours 
prior to the administration of study treatments on Day 1 and continue through 24 hours after the 
administration of study treatments on Days 1, 6, 15, and 16 and at corresponding timepoints on 
the day before dosing, ie, Day -1. Blood samples for PK analysis will be collected predose and at 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day ‐2
(Check‐in)
Inpatient Treatment Period
Day ‐28 
to ‐3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day ‐1
Day 2


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Protocol Version 2.0, 10 May 2021  
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each postdose cardiodynamic ECG timepoint. Additional PK samples will be collected at 72 and 
96 hours following dosing on Day 15. Subjects will return to the study site for a follow-up visit 
on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 16. 
The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. Pharmacokinetic 
blood samples will be collected at the following timepoints: prior to dosing and 0.5, 1, 2, 3, 4, 6, 
8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16; sample 
collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 
hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 12 to 24 hours 
postdose). Additional PK samples will be collected at 72 and 96 hours following dosing on Day 
15 (sample collection window: ±30 minutes). Subjects will be inactive and in a supine position 
for at least 10 minutes prior to and 5 minutes after each cardiodynamic ECG extraction 
timepoint, which will end immediately prior to the PK sampling. When timepoints for ECG 
extraction, safety ECGs, vital sign measurements, and blood draws coincide, procedures will be 
performed in said order. At each timepoint, up to 10 ECG replicates will be extracted from a 5-
minute time window (the last 5 minutes of the 15-minute period when the subject is maintained 
in a supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and sent to 
the central ECG laboratory for review. Resting ECGs to be used in the analyses will be selected 
from predetermined timepoints specified above and will be read by the central ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, and 
physical examination findings will be performed at screening and at specific timepoints during 
the study, and/or at the follow-up visit. In addition, subjects will be monitored via cardiac 
telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of enrollment 
occurs at the time of subject number allocation. The end of the study is defined as the date of the 
last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 


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Section 3.3, Selection of Doses in the Study 
Previously read: 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To carefully 
monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 doses will 
be up-titrated as follows: subjects will receive a starting dose of 0.1 mg CBP-307 on Day 1 
followed by an up-titrated dose of 0.2 mg on Days 2 to 5. Prior clinical experience with CBP-307 
has not demonstrated clinically significant abnormalities in laboratory test results in the majority 
of subjects or a dose-response relationship for safety based on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the characteristics 
of the study design with the safety of healthy subjects. Testing of CBP-307 at substantial 
multiples of the anticipated maximum therapeutic exposure is not clinically warranted due to the 
known safety and tolerability profile of CBP-307.  
Further details are provided in the IB.1 
Now reads: 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To carefully 
monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 doses will 
be up-titrated as follows: subjects will receive a starting dose of 0.05 mg CBP-307 on Day 1 
followed by an up-titrated dose of 0.1 mg on Day 2 and a dose of 0.2 mg on Days 3 to 6. Prior 
clinical experience with CBP-307 has not demonstrated clinically significant abnormalities in 
laboratory test results in the majority of subjects or a dose-response relationship for safety based 
on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the characteristics 
of the study design with the safety of healthy subjects. Testing of CBP-307 at substantial 
multiples of the anticipated maximum therapeutic exposure is not clinically warranted due to the 
known safety and tolerability profile of CBP-307.  
Further details are provided in the IB.1 


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Section 5.1, Investigational Products, Table 3 
Previously read: 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Formulation 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.1 mg 
Not applicable 400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.1 mg 
 
 
1 tablet 
Group 2A 
 
1 capsule 
1 × 400 mg 
 
Group 2B 
 
1 capsule 
 
1 tablet 
Days 2 to 5 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 6 to 14 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 15 Group 1 
 
 
 
1 tablet 
Group 2A 
 
 
 
1 tablet 
Group 2B 
 
 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Accountability 
 
The 
quantity 
administere
d, date 
administere
d, and lot 
number of 
investigatio
nal product 
is to be 
recorded on 
each 
subject's 
electronic 
case report 
form 
(eCRF). 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
eCRF. 
Dosing Instructions 
 
Treatments 
will be 
administere
d after the 
completion 
of all 
predose 
procedures 
and after a 
fast of at 
least 10 
hours with 
approximat
ely 240 mL 
of room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Now reads: 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 
400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
 
 
1 tablet 
Group 2A 
 
 
 
1 tablet 
Group 2B 
 
 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
electronic case 
report form 
(eCRF). 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot number 
of 
investigational 
product is to 
be recorded on 
each subject's 
eCRF. 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures and 
after a fast of 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
at least 10 
hours with 
approximately 
240 mL of 
room 
temperature 
water. 
at least 10 
hours with 
approximately 
240 mL of 
room 
temperature 
water. 
at least 10 
hours with 
approximately 
240 mL of 
room 
temperature 
water. 
at least 10 
hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Section 6.2, Diet 
Previously read: 
While confined at the study site, subjects will receive a standardized diet at scheduled times that 
do not conflict with other study-related activities. Subjects will be fasted overnight (at least 
10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be allowed 
from 7 days prior to check-in until follow-up visit on Day 28±2 days. 
Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 16. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge on 
Day 16 and alcohol intake will be limited to a maximum of 2 units/day on all other days, whilst 
not at the study site, from screening to 72 hours prior to the follow-up visit on Day 28±2 days.  
Now reads: 
While confined at the study site, subjects will receive a standardized diet at scheduled times that 
do not conflict with other study-related activities. Subjects will be fasted overnight (at least 
10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be allowed 
from 7 days prior to check-in until follow-up visit on Day 29±2 days. 


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Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 19. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge on 
Day 19 and alcohol intake will be limited to a maximum of 2 units/day on all other days, whilst 
not at the study site, from screening to 72 hours prior to the follow-up visit on Day 29±2 days.  
Section 6.4, Exercise 
Previously read: 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 28±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
Now reads: 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 29±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
Section 7, Study Assessments and Procedures, paragraph 3 
Previously read: 
This study includes a screening period (Day -28 to Day -2), a treatment period (Days -1 to 16), 
and a follow-up period (Day 28 ±2 days).  
Now reads: 
This study includes a screening period (Day -28 to Day -3), a treatment period (Days -2 to 19), 
and a follow-up period (Day 29 ±2 days).  
Section 7.2.3, Cardiac Telemetry Monitoring 
Previously read: 
NA 
Now reads: 
Subjects will be monitored via cardiac telemetry from approximately 1 hour prior to dose 
administration and until approximately 12 hours postdose on Days 1, 2, 3, and 7 (up-titration 
days; as described in Appendix 6). Based on the emerging safety data from the study, the 
duration of the telemetry may be extended if necessary. 


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The start and stop date and time of the telemetry monitoring will be recorded in the eCRFs. 
Clinically significant abnormalities noted from telemetry monitoring will be confirmed by 
12 lead ECG if necessary, then after confirming, the abnormalities will be reported as AEs in the 
eCRF. 
Section 8.3, Cardiodynamic ECG Analyses  
Previously read: 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus placebo 
in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
 Group 2A: For moxifloxacin administered on Day 1, baseline will be Day 15, on which 
subjects are administered placebo. For placebo-correction in this group, placebo values 
will be derived from Day 14 on which subjects are administered placebo, and baseline 
will be obtained on Day -1. 
 Group 2B: For moxifloxacin administered on Day 15, baseline will be Day 1, on which 
subjects are administered placebo. For the placebo-correction in this group, Day -1 values 
will be used as placebo (no treatment) and baseline will be obtained on Day 14. 
Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as the 
dependent variable, time-matched concentrations of CBP-307 as the exploratory variate (0 for 
placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on Days 1, 5, 
and 14 categorical) as fixed effects, and a random intercept and slope per subject.6  
The degrees of freedom estimates will be determined by the Kenward-Roger method. From the 
model, the slope (ie, the regression parameter for the CBP-307 concentration) and the treatment 
effect-specific intercept will be estimated together with 2-sided 90% CI. The estimates for the 
time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-time point analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 5, and 
14, and Days 1 and 15 for active versus placebo and moxifloxacin versus placebo, respectively. 
All times are relative to the time of dosing on that day which is considered the first dose for the 
assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the first dose of study 
treatment is on Day 1. 


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The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in the 
active drug groups on each of Days 5 and 14 will be determined, respectively. The predicted 
effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF (ΔΔQTcF) (ie, 
slope estimate × concentration + treatment effect-specific intercept) at this geometric mean Cmax 
will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the observed 
ΔQTcF values adjusted by population time effect estimated from the model will be used. These 
individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed individual ΔQTcFi,k 
for subject i administered with active drug or placebo at timepoint k minus the estimated 
population mean placebo effect at timepoint k (ie, time effect). A decile plot, ie, plot of the 
deciles of observed concentrations and the mean placebo-adjusted ΔQTcF (ΔΔQTcF) and 90% 
CI at the median concentration within each decile will be given. The regression line presenting 
the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a linear model and visualize 
the concentration-response relationship. The placebo-adjusted ΔQTcFi,j equals the individual 
ΔQTcFi,j for subject i administered with CBP-307 at timepoint j minus the estimation of time at 
timepoint j (ie, time effect). Additional exploratory analyses (via graphical displays and/or model 
fitting) will include accounting for a delayed effect (hysteresis) and the justification for the 
choice of PD model (linear versus nonlinear) as follows. 
Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the observed 
geometric mean Cmax on Days 5 and 14 as well as clinically relevant plasma levels is below 10 
msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax <10 msec), it can be 
concluded that CBP-307 does not cause clinically concerning QT prolongation within the 
observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 5 and 14; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on Days 5 
and 14; and if the difference (delay) between the time to reach the peak QTc effect (ΔΔQTcF) 
and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of more than 1 hour 
is observed in a consistent way for the active dose groups on Days 5 and 14, other concentration-
QTc models, such as a model with an effect compartment, may be explored. With the provision 
stated above, hysteresis will be assumed if this curve shows a counterclockwise loop. A 
significant treatment effect-specific intercept may also be indicative of hysteresis or model 
misspecification, if it cannot be explained by a nonlinear relationship. 


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Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 
time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a scatter 
plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI and a linear 
regression line will also be provided to check the assumption of a linear concentration-QTc 
relationship. If there is an indication that a linear model is inappropriate, additional models may 
be fitted, such as an E-max model. The concentration-QTc analysis will then be repeated for the 
model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of moxifloxacin 
data. If the slope of the concentration-QTc (change-from-baseline QTcF) for moxifloxacin is 
statistically significant at 10% level for 2-sided test and the lower bound of the 2-sided 90% CI 
of the predicted effect is above 5 msec at the observed geometric mean Cmax of the 400-mg dose, 
assay sensitivity will be deemed to have been demonstrated. 
By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 5, and 14: categorical), treatment (therapeutic dose of CBP-
307 and supratherapeutic dose of CBP-307 on Day 14, and corresponding placebo), and time-by-
treatment interaction as fixed effects. An unstructured covariance matrix will be specified for the 
repeated measures at postdose timepoints within subjects. If the model with unstructured 
covariance matrix fails to converge, other covariance matrices such as compound symmetry and 
autoregressive will be considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs 
will be calculated for the contrast “CBP-307 versus placebo” for each day of Days 1, 5, and 14 at 
each postbaseline timepoint on Days 1, 5, and Day 14, respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo at 
postbaseline timepoints on Day 1 and Day 15. A linear mixed-effects model will be used with 
ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 15: 
categorical), treatment (moxifloxacin and placebo), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. An unstructured 
covariance matrix will be specified for the repeated measures at postbaseline timepoints for 
subject within visit. The model will also include a subject-specific random effect. If the model 
with an unstructured covariance matrix fails to converge, other covariance matrices, such as 
compound symmetry or autoregressive, will be considered. From this analysis, the LS mean, SE, 
and 2-sided 90% CIs will be calculated for the contrast “moxifloxacin versus placebo” at each 
postbaseline timepoint, respectively. 


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For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline postdose 
(ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as described for 
QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both change-from-
baseline and placebo-corrected change-from-baseline values will be listed in the tables and 
graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will be 
summarized in frequency tables with counts (percentages) for both the number of subjects and 
the number of timepoints. For categorical outliers, the number (percentage) of subjects as well as 
timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 and 
≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline >25% 
to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR >100 bpm will be 
determined. For T-wave morphology and U-wave presence, the analyses will be focused on 
change from baseline (ie, treatment-emergent changes). 
Now reads: 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus placebo 
in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
 Group 2A: For moxifloxacin administered on Day 1, baseline will be Day 16, on which 
subjects are administered placebo. For placebo-correction in this group, placebo values 
will be derived from Day 15 on which subjects are administered placebo, and baseline 
will be obtained on Day -1. 
 Group 2B: For moxifloxacin administered on Day 16, baseline will be Day 1, on which 
subjects are administered placebo. For the placebo-correction in this group, Day -1 values 
will be used as placebo (no treatment) and baseline will be obtained on Day 15. 
Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as the 
dependent variable, time-matched concentrations of CBP-307 as the exploratory variate (0 for 
placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on Days 1, 6, 
and 15 categorical) as fixed effects, and a random intercept and slope per subject.6  
The degrees of freedom estimates will be determined by the Kenward-Roger method. From the 
model, the slope (ie, the regression parameter for the CBP-307 concentration) and the treatment 


Protocol Amendment 1 
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Covance Study: 8463245 
Protocol Reference: CBP-307AU002 
 
Protocol Version 2.0, 10 May 2021  
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effect-specific intercept will be estimated together with 2-sided 90% CI. The estimates for the 
time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-time point analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 6, and 
15, and Days 1 and 16 for active versus placebo and moxifloxacin versus placebo, respectively. 
All times are relative to the time of dosing on that day which is considered the first dose for the 
assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the first dose of study 
treatment is on Day 1. 
The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in the 
active drug groups on each of Days 6 and 15 will be determined, respectively. The predicted 
effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF (ΔΔQTcF) (ie, 
slope estimate × concentration + treatment effect-specific intercept) at this geometric mean Cmax 
will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the observed 
ΔQTcF values adjusted by population time effect estimated from the model will be used. These 
individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed individual ΔQTcFi,k 
for subject i administered with active drug or placebo at timepoint k minus the estimated 
population mean placebo effect at timepoint k (ie, time effect). A decile plot, ie, plot of the 
deciles of observed concentrations and the mean placebo-adjusted ΔQTcF (ΔΔQTcF) and 90% 
CI at the median concentration within each decile will be given. The regression line presenting 
the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a linear model and visualize 
the concentration-response relationship. The placebo-adjusted ΔQTcFi,j equals the individual 
ΔQTcFi,j for subject i administered with CBP-307 at timepoint j minus the estimation of time at 
timepoint j (ie, time effect). Additional exploratory analyses (via graphical displays and/or model 
fitting) will include accounting for a delayed effect (hysteresis) and the justification for the 
choice of PD model (linear versus nonlinear) as follows. 
Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the observed 
geometric mean Cmax on Days 6 and 15 as well as clinically relevant plasma levels is below 10 
msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax <10 msec), it can be 
concluded that CBP-307 does not cause clinically concerning QT prolongation within the 
observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 6 and 15; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on Days 6 


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and 15; and if the difference (delay) between the time to reach the peak QTc effect (ΔΔQTcF) 
and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of more than 1 hour 
is observed in a consistent way for the active dose groups on Days 6 and 15, other concentration-
QTc models, such as a model with an effect compartment, may be explored. With the provision 
stated above, hysteresis will be assumed if this curve shows a counterclockwise loop. A 
significant treatment effect-specific intercept may also be indicative of hysteresis or model 
misspecification, if it cannot be explained by a nonlinear relationship. 
Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 
time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a scatter 
plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI and a linear 
regression line will also be provided to check the assumption of a linear concentration-QTc 
relationship. If there is an indication that a linear model is inappropriate, additional models may 
be fitted, such as an E-max model. The concentration-QTc analysis will then be repeated for the 
model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of moxifloxacin 
data. If the slope of the concentration-QTc (change-from-baseline QTcF) for moxifloxacin is 
statistically significant at 10% level for 2-sided test and the lower bound of the 2-sided 90% CI 
of the predicted effect is above 5 msec at the observed geometric mean Cmax of the 400-mg dose, 
assay sensitivity will be deemed to have been demonstrated. 
By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 
time-by-treatment interaction as fixed effects. An unstructured covariance matrix will be 
specified for the repeated measures at postdose timepoints within subjects. If the model with 
unstructured covariance matrix fails to converge, other covariance matrices such as compound 
symmetry and autoregressive will be considered. From this analysis, the LS mean, SE, and 2-
sided 90% CIs will be calculated for the contrast “CBP-307 versus placebo” for each day of 
Days 1, 6, and 15 at each postbaseline timepoint on Days 1, 6, and Day 15, respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo at 
postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used with 
ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 16: 


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categorical), treatment (moxifloxacin and placebo), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. An unstructured 
covariance matrix will be specified for the repeated measures at postbaseline timepoints for 
subject within visit. The model will also include a subject-specific random effect. If the model 
with an unstructured covariance matrix fails to converge, other covariance matrices, such as 
compound symmetry or autoregressive, will be considered. From this analysis, the LS mean, SE, 
and 2-sided 90% CIs will be calculated for the contrast “moxifloxacin versus placebo” at each 
postbaseline timepoint, respectively. 
For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline postdose 
(ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as described for 
QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both change-from-
baseline and placebo-corrected change-from-baseline values will be listed in the tables and 
graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will be 
summarized in frequency tables with counts (percentages) for both the number of subjects and 
the number of timepoints. For categorical outliers, the number (percentage) of subjects as well as 
timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 and 
≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline >25% 
to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR >100 bpm will be 
determined. For T-wave morphology and U-wave presence, the analyses will be focused on 
change from baseline (ie, treatment-emergent changes). 
Section 8.4, Pharmacokinetic Analyses, paragraph 2 
Previously read: 
For each subject, the following PK parameters will be calculated, whenever possible, based on 
the plasma concentration for CBP-307 and moxifloxacin, according to the model independent 
approach: 
 Cmax 
 tmax 
 AUC0-24  
 AUCinf 
 apparent terminal elimination rate constant (λZ) 
 t1/2  


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 apparent total clearance (CL/F) 
 apparent volume of distribution during the terminal phase (Vz/F)  
Now reads: 
For each subject, the following PK parameters will be calculated, whenever possible, based on 
the plasma concentration for CBP-307 and moxifloxacin, according to the model independent 
approach: 
 Cmax 
 tmax 
 AUC0-24  
 AUCinf 
 apparent terminal elimination rate constant (λZ) 
 t1/2  
 apparent total clearance (CL/F) 
 apparent volume of distribution during the terminal phase (Vz/F)  
 Accumulation ratio (Rac) for Cmax (Rac[Cmax]) and Rac(AUC0-24), calculated as Day 15 
Cmax/Day 7 Cmax and Day 15 AUC0-24/Day 7 AUC0-24, respectively. 
 
Appendix 2: Clinical Laboratory Evaluations, Footnote “b” 
Previously read: 
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-
up visit (on Day 28±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  
Now reads: 
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-
up visit (on Day 29±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  


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Appendix 3: Total Blood Volume 
Previously read: 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
40 
320 
Total: 
382.5 
Now reads: 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
41 
328 
Total: 
390.5 
 


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Appendix 6: Schedule of Assessments 
Previously read: 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-up 
Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 to 4 
5 
6 to 13 
14 
15 
16 
28±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Admission to clinical research 
unit1 
 
X 
 
 
 
 
 
 
 
 
 
Discharge from clinical research 
unit2  
 
 
 
 
 
 
 
 
 
X 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height/weight/BMI 
X 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
 
 
 
 
 
 
 
 
X 
Hematology 
X 
X 
 
 
 
X 
 
 
 
X 
X 
Clinical chemistry  
(including cholesterol panel tests) 
X 
X 
 
 
 
X 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, or 
HCVAb 
X 
 
 
 
 
 
 
 
 
 
 
12-lead safety electrocardiogram4,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
 
 
 
 
 
 
 
 
 
Cardiodynamic monitoring 
(Holter)/replicate ECG extraction5 
 
 
X 
X 
 
X 
 
X 
X 
 
 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-up 
Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 to 4 
5 
6 to 13 
14 
15 
16 
28±2 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
X 
Follicle -stimulating hormone test 
(postmenopausal females only) 
X 
 
 
 
 
 
 
 
 
 
 
CBP-307/placebo administration 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
Moxifloxacin/placebo 
administration 
 
 
 
X 
 
 
 
 
X 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
X 
 
X 
X 
 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).  
2. Discharge from unit will occur after the 24-hour PK samples and after completion of safety assessments on Day 16. 
3. Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Day 16): 
Prior to and 2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Discharge (Day 16): Prior to 
discharge, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 28±2 days): 
Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. 
4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days and before discharge on Day 16. Postdose 
safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 5, 14, and 15. The recording will be started at least 1 
hour before dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an 
undisturbed environment. When timepoints for ECG extraction, safety ECGs, vital signs assessment, and blood draws coincide, procedures will be 
performed in this order. The ECG effects of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 5 (therapeutic concentrations versus 
placebo), and Day 14 (supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 14, and 
15. 
6. Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 28±2 days). A 
positive urine pregnancy test will be confirmed with a serum pregnancy test. 
7. Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 5, 14, 
and 15). 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 
to 8 hours postdose, and ±30 minutes for 12 to 24 hours postdose. 


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Now reads: 
Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinical 
research unit1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from clinical 
research unit2  
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height/weight/BMI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematology 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Clinical chemistry  
(including cholesterol 
panel tests) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, 
or HCVAb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead safety 
electrocardiogram4,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Cardiac Telemetry 
Monitoring9 
 
 
 
X 
X 
X 
(Day 3) 
 
X 
 (Day 7) 
 
 
 
 
 
 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
 
 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Follicle -stimulating 
hormone test 
(postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBP-307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Moxifloxacin/placebo 
administration 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).  
2. Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19. 
3. Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 
18, and 19): Prior to and 2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: 
Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to 
discharge, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): 
Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. 
4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before 
discharge on Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 
hour before dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing 
(-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an 
undisturbed environment. When timepoints for ECG extraction, safety ECGs, vital signs assessment, and blood draws coincide, procedures will be 
performed in this order. The ECG effects of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus 


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placebo), and Day 15 (supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 
16. 
6. Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 29±2 days). A 
positive urine pregnancy test will be confirmed with a serum pregnancy test. 
7. Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, 
and 16). Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 hours postdose, ±10 minutes for 
6 to 8 hours postdose, and ±30 minutes for 12 to 24, 72, and 96 hours postdose. 
9. Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 
12 hours postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended 
if necessary. The start and stop date and time of the telemetry monitoring will be recorded in the eCRF. 
 
 


TITLE PAGE 
Protocol 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, 
Placebo- and Positive-Controlled Study to Investigate the Effects of 
CBP-307 on the QTC Interval in Healthy Subjects 
Protocol Amendment 1 Status: Final 
Original Protocol Date: 18 March 2021 
Protocol Amendment Date: 10 May 2021 
Protocol Version: 2.0 
Investigational Medicinal Product: CBP-307 
 
Protocol Reference Number: CBP-307AU002 
Covance Study Number: 8463245 
IND Number: 134585 
 
 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Site: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
 
 
Sponsor Signatory: 
Ping Li, MD 
 
Principal Investigator: 
Nicholas Farinola, MBBS 
 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


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SPONSOR APPROVAL 
I have read the protocol and approve it: 
 
 
 
 
 
 
 
Ping Li, MD 
 
Date 
VP, Clinical Development Asia 
DocuSign Envelope ID: 6160160A-DBDE-45CB-89F3-92B50E107DBE
2021/5/13
u==·u 
1G66680666GD4EA ... 


Protocol Amendment 1 
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INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
Nicho s Farinola, MBBS 
Principal Investigator 
Protocol Version 2.0, 10 May 2021 
Date 
Page 3 of66 


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STUDY IDENTIFICATION 
Sponsor 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu 215400 
China 
Sponsor’s Study Contact 
Max Meng, BS 
Project Manager 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Tel: +86 0512 5357 7866 
Email: yhmeng@connectpharm.com 
Sponsor’s Medical Contact 
Jane Royalty, MD 
Covance Clinical Research Unit, Inc. 
3402 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 
Tel: 812-474-5015 
Email: jane.royalty@covance.com 
Study Site  
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Principal Investigator 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 
Clinical Laboratory  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 


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Bioanalytical Laboratory 
Peter Tapley 
Director, TetraQ 
The University of Queensland 
Level 7, Block 6, RBWH 
Herston, Queensland 4029  
Australia 
Statistician 
Wei Xiao, MS 
Covance Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 


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SYNOPSIS 
Study Title 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and Positive-
Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in Healthy 
Subjects 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the pharmacokinetics (PK) of CBP-307 following administration of 
therapeutic and supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on heart rate (HR), PR and QRS intervals, and T-wave morphology. 
Study Design 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only serious 
adverse events (SAEs) will be reported. After placebo administration to all subjects on 
Day -1, all adverse events (AEs), whether volunteered, elicited, or noted upon physical 
examination, will be recorded throughout the study (ie, from Day -1 until the end of the 
study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 


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Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic electrocardiogram (ECG) monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 6, 15, 
and 16 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15. Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. When timepoints for ECG extraction, safety ECGs, vital sign measurements, and 
blood draws coincide, procedures will be performed in said order. At each timepoint, up to 


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10 ECG replicates will be extracted from a 5-minute time window (the last 5 minutes of the 
15-minute period when the subject is maintained in a supine, quiet position). The ECG effects 
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic 
concentrations versus placebo), and Day 15 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be evaluated using ECG data collected on Days -1, 
1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
Number of Subjects 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Diagnosis and Main Criteria for Inclusion 
Healthy male and female subjects aged between 18 and 60 years (inclusive) with a body mass 
index between 18.0 and 30.0 kg/m2 (inclusive). 
Investigational Medicinal Products, Dose, and Mode of Administration 
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 titrated to 0.1 mg on 
Day 2; oral capsule) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6; oral capsule) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15; oral capsule) 
• Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 


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• Moxifloxacin (400 mg; oral tablet). 
Duration of Subject Participation in the Study 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3), 21 days for the in-house 
treatment period (Days -2 to 19), and 10 ±2 days for follow-up (Day 29±2 days), in total 
approximately 59 days. 
Endpoints 
Electrocardiogram (Cardiodynamic): 
The primary cardiodynamic endpoint is the change-from-baseline QTcF (ΔQTcF). 
The secondary cardiodynamic endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
Pharmacokinetics: 
Blood samples will be collected for the analysis of plasma concentrations of CBP-307. The 
PK parameters of CBP-307 will be calculated using a model independent approach. The 
following PK parameter endpoints will be calculated: maximum observed concentration 
(Cmax), area under the concentration-time curve from time zero extrapolated to infinity 
(AUCinf), area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24), and time of the maximum observed concentration (tmax). Other noncompartmental 
parameters may be reported. 
Safety: 
Adverse events, clinical laboratory evaluations (hematology, clinical chemistry, urinalysis), 
12lead ECGs, and vital signs measurements. 
Statistical Methods 
Cardiodynamic evaluation: 
The primary analysis will be based on concentration-QTc modeling of the relationship 
between plasma concentrations of CBP-307 and change-from-baseline QTcF (∆QTcF) with 
the intent to exclude an effect of placebo-corrected ΔQTcF (ΔΔQTcF) > 10 msec at clinically 


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relevant plasma levels. Placebo-corrected ΔHR, ΔPR, ΔQRS, and ∆QTcF (ΔΔHR, ΔΔPR, 
ΔΔQRS, and ∆∆QTcF) will also be evaluated at each postdosing timepoint ('by-timepoint' 
analysis). An analysis of categorical outliers will be performed for changes in HR, PR, QRS, 
QTcF, T-wave morphology, and U-wave presence. Assay sensitivity will be evaluated by 
concentration-QTc analysis of the effect on ∆ΔQTcF of moxifloxacin using a similar model 
as for the primary analysis. 
Pharmacokinetics: 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, standard deviation, median, 
minimum, maximum geometric mean, and geometric coefficient of variation) separately by 
cohort. Individual and mean plasma CBP-307 and moxifloxacin concentration versus time 
data will be tabulated and plotted by dose level. Graphical displays of PK data may be 
provided as well.  
Pharmacokinetic/electrocardiography analyses: 
The relationship between CBP-307 plasma concentrations and the change from ∆QTcF will 
be evaluated using a linear mixed-effects modeling approach. 
Safety: 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12lead ECGs, vital signs, and physical 
examination findings will be listed. 


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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SPONSOR APPROVAL ...........................................................................................................2 
INVESTIGATOR AGREEMENT.............................................................................................3 
STUDY IDENTIFICATION .....................................................................................................4 
SYNOPSIS .................................................................................................................................6 
TABLE OF CONTENTS .........................................................................................................11 
LIST OF TABLES AND FIGURES........................................................................................14 
LIST OF ABBREVIATIONS ..................................................................................................15 
1.
INTRODUCTION ...........................................................................................................17 
1.1. 
Disease Background...............................................................................................17 
1.2. 
Overview of CBP-307............................................................................................17 
1.2.1. 
Summary of Clinical Experience .................................................................17 
1.2.1.1. 
Safety .................................................................................................18 
1.2.1.2. 
Pharmacokinetics ...............................................................................20 
1.3. 
Overview of Moxifloxacin .....................................................................................21 
1.4. 
Study Rationale ......................................................................................................21 
1.5. 
Benefit-risk Assessment .........................................................................................22 
2.
OBJECTIVES AND ENDPOINTS .................................................................................22 
2.1. 
Objectives ..............................................................................................................22 
2.2. 
Endpoints ...............................................................................................................22 
2.2.1. 
Electrocardiogram Endpoints .......................................................................22 
2.2.1.1. 
Primary ...............................................................................................22 
2.2.1.2. 
Secondary ...........................................................................................22 
2.2.2. 
Pharmacokinetic Endpoints .........................................................................23 
2.2.3. 
Safety Endpoints ..........................................................................................23 
3.
INVESTIGATIONAL PLAN ..........................................................................................23 
3.1. 
Overall Study Design and Plan ..............................................................................23 
3.2. 
Discussion of Study Design ...................................................................................26 
3.3. 
Selection of Doses in the Study .............................................................................26 
4.
SELECTION OF STUDY POPULATION .....................................................................27 
4.1. 
Inclusion Criteria ...................................................................................................27 
4.2. 
Exclusion Criteria ..................................................................................................27 
4.3. 
Subject Number and Identification ........................................................................30 
4.4. 
Subject Withdrawal and Replacement ...................................................................30 
4.5. 
Study Termination .................................................................................................31 
5.
STUDY TREATMENTS .................................................................................................31 
5.1. 
Investigational Products .........................................................................................31 
5.2. 
Study Treatment Administration ............................................................................33 


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5.3. 
Randomization .......................................................................................................33 
5.4. 
Blinding..................................................................................................................34 
5.5. 
Treatment Compliance ...........................................................................................34 
5.6. 
Drug Accountability...............................................................................................34 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................35 
6.1. 
Concomitant Therapies ..........................................................................................35 
6.2. 
Diet .........................................................................................................................35 
6.3. 
Smoking .................................................................................................................36 
6.4. 
Exercise ..................................................................................................................36 
6.5. 
Blood Donation ......................................................................................................36 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................36 
7.1. 
General Assessments .............................................................................................37 
7.1.1. 
Demographics ..............................................................................................37 
7.1.2. 
Medical History ...........................................................................................37 
7.2. 
Electrocardiography Assessments .........................................................................37 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording ......................................37 
7.2.1.1. 
TQT Plus Extraction Technique ........................................................37 
7.2.1.2. 
Expert Precision QT Analysis ............................................................38 
7.2.2. 
Safety 12-lead Electrocardiogram ................................................................38 
7.2.3. 
Cardiac Telemetry Monitoring ....................................................................39 
7.3. 
Pharmacokinetic Assessments ...............................................................................39 
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................39 
7.3.2. 
Analytical Methodology ..............................................................................39 
7.4. 
Safety and Tolerability Assessments .....................................................................39 
7.4.1. 
Adverse Events ............................................................................................39 
7.4.2. 
Clinical Laboratory Evaluations ..................................................................40 
7.4.3. 
Vital Signs ....................................................................................................40 
7.4.4. 
Physical Examination...................................................................................40 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................41 
8.1. 
Determination of Sample Size ...............................................................................41 
8.2. 
Analysis Populations ..............................................................................................42 
8.2.1. 
Cardiodynamic Population...........................................................................42 
8.2.2. 
Pharmacokinetic Population ........................................................................42 
8.2.3. 
Safety Population .........................................................................................42 
8.3. 
Cardiodynamic ECG Analyses ..............................................................................42 
8.4. 
Pharmacokinetic Analyses .....................................................................................45 
8.5. 
Safety Analysis ......................................................................................................46 
8.6. 
Interim Analysis .....................................................................................................46 
9. 
REFERENCES ................................................................................................................46 


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10. APPENDICES .................................................................................................................48 
Appendix 1: Adverse Event Reporting ..............................................................................49 
Appendix 2: Clinical Laboratory Evaluations ...................................................................54 
Appendix 3: Total Blood Volume ......................................................................................55 
Appendix 4: Contraception Guidance ................................................................................56 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations ............................59 
Appendix 6: Schedule of Assessments ..............................................................................63 
 


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LIST OF TABLES AND FIGURES 
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................20 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................21 
Table 3: Study Treatments .................................................................................................32 
Figure 1: Study Schematic .................................................................................................24 


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LIST OF ABBREVIATIONS 
Abbreviation Definition 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUCinf 
area under the concentration-time curve from time zero extrapolated to 
infinity 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours 
postdose 
CI 
confidence interval 
CL/F 
apparent total clearance 
Cmax 
maximum observed concentration 
CRO 
contract research organization 
CYP 
cytochrome P450 
Δ 
change-from-baseline 
ΔΔ 
placebo-corrected or placebo-adjusted change-from-baseline 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
HR 
heart rate 
HREC 
human resource ethics committee 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
IP 
investigational product 
LOESS 
locally estimated scatterplot smoothing 
LS 
least squares 
PK 
pharmacokinetic(s) 
PD 
pharmacodynamic(s) 
QD 
once daily 
QTc 
heart-corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
Rac 
accumulation ratio  
Rac(Cmax) 
accumulation ratio for Cmax 


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Rac(AUC0-24) 
accumulation ratio for AUC0-24 
SAE 
serious adverse event 
SD 
standard deviation 
SE 
standard error 
S1P1 
sphingosine-1-phosphate receptor 1 
TEAE 
treatment-emergent adverse event(s) 
t1/2 
apparent terminal elimination half-life 
tmax 
time of the maximum observed concentration 
TQT 
thorough QT 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
λZ 
apparent terminal elimination rate constant 
 
 


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1. INTRODUCTION 
Refer to the investigator’s brochure (IB)1 for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile 
of the investigational medicinal product (IMP). 
1.1. 
Disease Background 
Autoimmune diseases are serious disorders that afflict a large portion of the world 
population; most have no cures. Significant advances have been made in the development of 
novel and disease-modifying therapies, but many of these new treatments have significant 
side effects. Treatments are needed that provide better risk-to-benefit profiles than the 
existing therapeutic choices. 
T cells are important immune cells that mediate the development of autoimmune disorders. 
Migration of T cells from lymphoid tissues to the sites of inflammation is central to the 
functions of T cells, and this process is dependent on sphingosine-1-phosphate (S1P) receptor 
1 (S1P1) which is known to ameliorate a variety of autoimmune diseases in animals and 
humans. Down modulation of this receptor, using S1P1 agonists, prevents T cell egress and 
results in a reduced number of circulating lymphocytes, particularly the CD4+- and CD8+-
naïve and central-memory T cell subsets.  
1.2. 
Overview of CBP-307 
CBP-307 is an S1P1 agonist that is being developed as a treatment for autoimmune diseases 
by Suzhou Connect Biopharmaceuticals, Ltd. CBP-307 (1-(2-fluoro-4-(5-(4-isobutylphenyl)-
1,2,4-oxadiazol-3-yl) benzyl) azetidine-3-carboxylic acid hemihydrate) is a potent, selective, 
small-molecule agonist of S1P1 and S1P5 receptors. Cell-based assays have confirmed 
CBP-307 induces internalization of S1P1 from the cell surface. This is consistent with the 
known mechanism of action of other S1P1 agonists, in that they down-modulate S1P1 and 
inhibit lymphocyte egress from lymphoid tissues.  
1.2.1. 
Summary of Clinical Experience 
The Phase 1 development of CBP-307 comprised 2 completed studies in healthy subjects: 
• A single and multiple ascending dose study to evaluate the safety and tolerability of 
CBP-307 including pharmacokinetic (PK), pharmacodynamic (PD), and food-effect 
assessments (Study CBP-307AU001) 
• A single-dose and multiple-dose, and fixed-dose titration study to evaluate the safety 
and tolerability of CBP-307 including PK and PD (Study CBP-307CN001) 
Currently, CBP-307 is being evaluated in 2 Phase 2 studies:  
• Ongoing multicenter study in subjects with moderate to severe ulcerative colitis 
(Study CBP-307CN002) to compare the clinical efficacy by evaluating the clinical 
response to CBP-307 versus placebo and the clinical remission and mucosal healing 


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achieved by CBP-307 versus placebo and to compare the clinical safety and 
tolerability of CBP-307 with those of placebo. 
• Ongoing study in subjects with moderate to severe Crohn’s disease compares clinical 
efficacy by evaluating the clinical response to CBP-307 versus placebo and the 
clinical remission and mucosal healing achieved by CBP-307 versus placebo and to 
compare the clinical safety and tolerability of CBP-307 with those of placebo. 
1.2.1.1. 
Safety 
Study CBP-307AU001 
A total of 44 healthy subjects were enrolled in the study. There were 28 subjects evaluated 
using the single-dose regimen (0.1, 0.25, 0.5, and 2.5 mg CBP-307) of which 21 subjects 
received CBP-307 and 7 subjects received placebo. Another 16 healthy subjects were 
evaluated using the multiple-dose regimen (0.15 and 0.25 mg CBP-307 given once daily 
[QD] for 28 consecutive days) of which 12 subjects received CBP-307 and 4 subjects 
received placebo. 
Overall, no unexpected safety signals were identified and no deaths occurred in this study. 
For the single-dose regiment, no subjects were discontinued due to a treatment-emergent AE 
(TEAE). In the multiple-dose regimen, there were 2 subjects who were discontinued from the 
study (due to increased alanine transaminase and second degree AV block [not considered to 
be clinically significant, as judged by the investigator]). All TEAEs resolved by the end of 
the study. 
In the single-dose regimen groups, TEAEs were reported in 12 of 21 subjects (57.1%) treated 
with CBP-307 and in 3 of 7 subjects (42.8%) treated with placebo. Most (91.7%) of the 
TEAEs in these subjects were mild in severity. The most common TEAEs in the 
CBP-307-treated groups were headache (28.6%); dizziness (19.0%); and bradycardia (9.5%). 
Bradycardia was reported only in 2 subjects receiving the highest (2.5 mg) CBP-307 dose. 
One subject had a serious adverse event (SAE) of bradycardia (associated with transient 
asystole) following a single dose of 2.5 mg CBP-307. 
In the multiple-dose regimen groups, CBP-307 at doses of 0.15 and 0.25 mg QD was 
generally well tolerated over the 28 days of dosing. Treatment-emergent AEs were reported 
in 11 of 12 subjects (91.7%) in the CBP-307 groups and 2 of 4 subjects (50.0%) in the 
placebo groups. Most (83.3%) TEAEs were mild in severity. The most common TEAEs in 
the 2 CBP-307 groups were headache (50.0%), and fatigue, nausea, and musculoskeletal pain 
(16.7% each). The incidences of these TEAEs were similar in both CBP-307-treated groups. 
No SAEs were reported for subjects in the multiple-dose regimen. 
Study CBP-307CN001 
A total of 30 eligible subjects completed 3 CBP-307 dose groups in ascending order of dose 
after randomization (in a ratio of 1:1:1): Group A (0.1 mg), Group B (0.2 mg), and Group C 
(0.3 mg). Each dose group consisted of 10 subjects, including 8 subjects receiving the 
investigational drug and 2 subjects receiving placebo by random assignment. The 
administration started from the dose of 0.1 mg. The subjects in this group received a single 


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dose of CBP-307 or placebo and were followed up for safety and tolerance within the next 
7 days. Then the subjects received 0.1 mg CBP-307 or placebo QD for 14 consecutive days 
and were followed up for safety and tolerance within the next 7 days. Dose escalation did not 
occur until the review of the single-dose regimen safety data from the 6 subjects in the 
previous dose cohort, and the safety data did not meet the termination criteria. The subjects in 
the dose of 0.3 mg received fixed-dose titration regimen, ie, 0.05 mg CBP-307 or placebo QD 
for 3 consecutive days; 0.1 mg CBP-307 or placebo QD for 2 consecutive days; 0.2 mg CBP-
307 or placebo QD for 2 consecutive days; finally, 0.3 mg CBP-307 or placebo QD for 
14 consecutive days, and the subjects were followed up for safety and tolerance within the 
next 7 days. 
Overall, no unexpected safety signals were identified, and there were no deaths, SAEs, or 
AEs leading to the subject’s early withdrawal from the study after administration of CBP-
307. In the safety set, a total of 29 subjects (8 in Group A, 100%; 8 in Group B, 100%; 8 in 
Group C, 100% and 5 in placebo group, 83.3%) experienced TEAEs. 
During the single-dose period, a total of 14 subjects (5 of 8 in Group A, 62.5%; 6 of 8 in 
Group B, 75%, and 3 of 4 in placebo group, 75%) developed AEs. The incidence of TEAEs 
in Group A was generally similar to the placebo group. Among TEAEs in Group B, the 
incidence of AEs related to abnormalities in investigations was higher than that in placebo 
group, including lymphocyte count decreased (12.5%), white blood cell (WBC) count 
decreased (12.5%), neutrophil count decreased (12.5%), alanine aminotransferase increased 
(25%), and gamma-glutamyltransferase increased (12.5%), and aspartate aminotransferase 
increased (12.5%). Additionally, 1 subject experienced heart rate (HR) decreased (12.5%). 
During dose-titration period, 2 subjects (2 of 8 in Group C, 25%) experienced TEAEs. The 
TEAEs reported in Group C during the titration period included cough (12.5%) and increased 
upper airway secretion (12.5%). There were no TEAEs in the placebo group during this 
period. 
During repeated-dose period, a total of 28 subjects (8 of 8 in Group A, 100%; 8 of 8 in Group 
B, 100%; 8 of 8 in Group C, 100%; and 4 of 6 in placebo group, 66.7%) experienced AEs. 
The most frequent TEAE in Group A was upper respiratory tract infection (37.5%) compared 
with placebo group; the most frequent TEAEs in Group B and Group C included decreased 
lymphocyte count (Group B, 87.5%; Group C, 100.0%), WBC count (Group B, 87.5%; 
Group C, 62.5%), and neutrophil count (Group B, 50%; Group C, 12.5%). The TEAEs noted 
in Group B during the repeated-dose period also included increased alanine aminotransferase 
(25%), gamma-glutamyltransferase (37.5%), and aspartate aminotransferase (12.5%), upper 
respiratory tract infection (12.5%), influenza (12.5%), chest pain (12.5%), lethargy (25%), 
and neck pain (12.5%); TEAEs in Group C during the repeated-dose period also included 
increased alanine aminotransferase (25%), decreased HR (12.5%), and mouth ulcer (12.5%); 
the TEAEs in placebo group included increased transaminase (16.7%), prolonged activated 
partial thromboplastin time (1/6, 16.7%), decreased hemoglobin (16.7%), upper respiratory 
tract infection (16.7%), diarrhea (16.7%), dizziness (16.7%), and palpitations (16.7%). 
Study CBP-307CN002 
This study is ongoing and there are no safety data available.  


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Study CBP-307CN003 
This study is ongoing and there are no safety data available.  
1.2.1.2. 
Pharmacokinetics 
CBP-307 given orally as a single dose was readily absorbed; drug concentrations peaked at 
approximately 6 hours after administration, with an elimination apparent terminal elimination 
half-life (t1/2) of approximately 25 hours (range of 23 to 29 hours). The time to maximum 
observed concentration (Cmax) in the blood was delayed from 6 hours to approximately 
10 hours when CBP-307 was given with a high-fat diet. Food consumption also increased 
exposure (Table 1). 
For the single-dose administration, CBP-307 exposure (based on Cmax and area under the 
concentration-time curve [AUCs]) increased with increasing dose following a single-dose 
administration (Table 1).  
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Single-Dose 
Regimen PK 
Parameters 
Mean CBP-307 Single Dose ± SEM (n) 
0.1 mg 
0.25 mg 
0.5 mg 
(fasted) 
0.5 mg (fed)a 
2.5 mg 
AUClast 
(ng*h/mL) 
13.4 ± 3.54 
(n = 6) 
45.1 ± 5.25 
(n = 6) 
160 ± 22.8 
(n = 6) 
290 ± 28.1 
(n = 6) 
550 ± 96.3 
(n = 3) 
AUCinf 
(ng*h/mL) 
ND 
63.7 ± 2.14 
(n = 3) 
214 ± 58.3 
(n = 3) 
355 ± 44.3 
(n = 5) 
710 ± 164 
(n = 2) 
Cmax 
(ng/mL) 
0.537 ± 0.0931 
(n = 6) 
1.53 ± 
0.0935 
(n = 6) 
4.84 ± 0.706 
(n = 6) 
8.58 ± 1.11 
(n = 6) 
19.0 ± 3.55 
(n = 3) 
tmax 
(hours) 
7.33 ± 1.33 
(n = 6) 
5.33 ± 0.99 
(n = 6) 
5.00 ± 0.86 
(n = 6) 
10.67 ± 2.72 
(n = 6) 
6.00 ± 2.00 
(n = 3) 
t1/2 
(hours) 
ND 
23.3 ± 1.70 
(n = 3) 
28.8 ± 1.28 
(n = 3) 
26.0 ± 1.17 
(n = 5) 
22.8 ± 3.96 
(n = 2) 
Abbreviations: AUCinf = area under the curve at infinity; AUClast = area under the curve at the last time point; 
Cmax = maximum concentration; h = hour(s); mg = milligram(s); ND = not determinable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SEM = standard error of the mean; T1/2 = elimination half-life; Tmax = time to maximum 
concentration.  
a Study Part 1b: Cohort 3 from Part 1a returned to receive a single oral dose of CBP-307 at 0.5 mg under fed conditions. 
Source: Final report for Study CBP-307AU001. 
For the repeated-dose administration of CBP-307, the Cmax and AUCs increased with the 
higher administered dose (Table 2). At the steady-state timepoint on Day 28, the median 
CBP-307 tmax was 4 to 6 hours. The average t1/2 was similar, ranging 44 to 49 hours, and 
there were no dose-dependent changes in t1/2 within the dose range. The t1/2 was slightly 
prolonged after repeated-dose administration when compared with that after a single-dose 
administration. Moderate accumulation of CBP-307 (approximately 3 times the levels 


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following a single dose) was noted in plasma after QD administration for 14 consecutive 
days. 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Multiple-Dose 
Regimen PK 
Parameters 
Multiple-Dose Cohort 1  
CBP-307 Dosing, mg (± SD) (n) 
Multiple-Dose Cohort 2  
CBP-307 Dosing, mg (± SD) (n) 
Day 1 
0.1  
Day 28 
0.25  
Day 1 
0.15  
Day 28 
0.15  
AUC0-24 
(ng*h/mL) 
24.5 ± 3.26 
(n = 5) 
125 ± 12.4 
(n = 4) 
26.3 ± 7.45 
(n = 5) 
79.7 ± 27.3 
(n = 6) 
AUClast 
(ng*h/mL) 
NA 
203 ± 21.9 
(n = 4) 
NA 
131 ± 44.7 
(n = 6) 
Cmax 
(ng/mL) 
1.45 ± 0.214 
(n = 5) 
6.30 ± 0.588 
(n = 4) 
1.32 ± 0.422 
(n = 6) 
4.23 ± 1.45 
(n = 6) 
tmax 
(hours) 
6.80 ± 1.50 
(n = 5) 
6.50 ± 1.50 
(n = 4) 
5.00 ± 0.68 
(n = 6) 
4.33 ± 0.33 
(n = 6) 
Abbreviations:  AUC0-24 = area under the curve from time 0 to 24 hours; AUClast = area under the curve at the last time 
point; Cmax = maximum concentration; mg = milligram(s); NA = not applicable; ng/mL = nanogram(s) per milliliter; PK = 
pharmacokinetic; SD = standard deviation; Tmax = time to maximum concentration. 
Source: Final report for Study CBP-307AU001. 
1.3. 
Overview of Moxifloxacin 
Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic that binds to and inhibits the 
hERG IKr α subunit and causes a mean increase of the QTc interval of 6 ms after a single 
400-mg oral dose. Moxifloxacin is commonly used as a positive control in thorough QT 
(TQT) studies to satisfy the requirements of International Council for/Conference on 
Harmonisation (ICH) E14. 
Refer to the regional manufacturer package insert of AVELOX (moxifloxacin hydrochloride) 
tablets for additional information.2 
1.4. 
Study Rationale 
Regulatory guidance (ICH E14) has emphasized the need to obtain clear robust data on the 
effect of new chemical entities on electrocardiogram (ECG) parameters with focus on cardiac 
repolarization as measured by the QTc duration. Though many Phase 1, 2, and 3 trials may be 
conducted they usually have an insufficient sample size, infrequent sampling of ECG data, or 
the use of inadequate controls to overcome the high rate of spontaneous change in QTc 
duration. This has resulted in regulatory guidance recommending a dedicated or thorough 
trial to define the ECG effects of new drugs. 
This study will be done in healthy subjects to eliminate variables known to have an effect on 
ECG parameters (concomitant drugs, diseases, etc.). A supratherapeutic dose of CBP-307 is 
required to mimic the exposure in healthy subjects that may occur in the target population 
under the worst of circumstances (eg, concomitant use of cytochrome P450 [CYP]3A4 


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inhibitor, concomitant liver disease, presence of heart disease, taking more than the clinical 
dose prescribed) and to allow for PK to QTc modeling to assess the effect of drug 
concentration on cardiac repolarization. 
1.5. 
Benefit-risk Assessment 
Healthy subjects in the current study will not receive any health benefit (beyond that of an 
assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from the collection of blood samples and other study 
procedures. More information about the known and expected benefits, risks, and reasonably 
anticipated AEs associated with CBP-307 may be found in the IB.1  
2. OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the PK of CBP-307 following administration of therapeutic and 
supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on HR, PR and QRS intervals, and T-wave morphology. 
2.2. 
Endpoints 
2.2.1. 
Electrocardiogram Endpoints 
2.2.1.1. 
Primary 
The primary endpoint is the change-from-baseline QTcF (ΔQTcF). 
2.2.1.2. 
Secondary  
The secondary endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 


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• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
2.2.2. 
Pharmacokinetic Endpoints 
Pharmacokinetic parameters of CBP-307 will be determined if data allows: 
• area under the concentration‑time curve from time zero extrapolated to infinity 
(AUCinf) 
• area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24) 
• maximum observed concentration (Cmax) 
• time of the maximum observed concentration (tmax) 
Other PK parameters may also be reported. 
2.2.3. 
Safety Endpoints 
The safety outcome measures for this study are as follows: 
• incidence and severity of AEs 
• incidence of laboratory abnormalities, based on hematology, clinical chemistry, and 
urinalysis test results 
• 12-lead ECG parameters 
• vital signs measurements. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only SAEs will be 
reported. After placebo administration to all subjects on Day -1, all AEs, whether 


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volunteered, elicited, or noted upon physical examination, will be recorded throughout the 
study (ie, from Day -1 until the end of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 
Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated 
dose of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec.  
An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 
32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 
16 subjects. Subjects will be randomized to receive a treatment sequence that includes 4 treatments (CBP-307 therapeutic 
dose, CBP-307 supratherapeutic dose, moxifloxacin, or placebo [matched to CBP-307 or moxifloxacin]); assigned study 
treatments will be administered on Day 1, Day 2, Days 3 to 6, Days 7 to 15, and Day 16. Dosing details are provided in 
Table 3. Blood samples for pharmacokinetic analysis will be collected predose and at each postdose cardiodynamic 
electrocardiogram timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. An 
end-of-study visit will occur on Day 29±2 days. 
Day 19
(Clinic 
Discharge)
Final 
Visit
(Day 29±2 
days)
Days 3 
to 6
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 7 
to 15
Day 16
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1
Day 2


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Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 19. Treatment administration will 
occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at 
least 25 hours prior to the administration of study treatments on Day 1 and continue through 
24 hours after the administration of study treatments on Days 1, 6, 15, and 16 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK 
analysis will be collected predose and at each postdose cardiodynamic ECG timepoint. 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
Subjects will return to the study site for a follow-up visit on Day 29±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. When timepoints for ECG extraction, safety ECGs, vital sign measurements, and 
blood draws coincide, procedures will be performed in said order. At each timepoint, up to 
10 ECG replicates will be extracted from a 5-minute time window (the last 5 minutes of the 
15-minute period when the subject is maintained in a supine, quiet position). The ECG effects 
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic 
concentrations versus placebo), and Day 15 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be evaluated using ECG data collected on Days -1, 
1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 


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The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
A Schedule of Assessments is presented in Appendix 6. 
3.2. 
Discussion of Study Design 
The purpose of this study is to evaluate the potential for CBP-307 to cause QT prolongation. 
As CBP-307 exposure affects heart rate, the primary endpoint for this study will be the QTcF. 
The study will be randomized and double-blind because randomization eliminates 
confounding by baseline variables and blinding eliminates confounding by co-interventions, 
thus eliminating the possibility that the observed effects of the intervention are because of 
differential use of other treatments.  
The sample size for this study is based on a formal statistical power calculation. 
Conducting the study in healthy subjects mitigates the potential confounding effects of the 
disease state and concomitant medications. Both male and female subjects will be included to 
eliminate similar known ECG variability effects. 
Additionally, because food has been shown to alter the PK of CBP-307, subjects will be 
fasted at least 10 hours prior to dose administration and remain fasted for 4 hours postdose on 
the days when PK samples are collected. 
Pharmacokinetic assessments of CBP-307 concentrations in plasma will be evaluated during 
the study. The timepoints for the PK sample collections are based on previous studies and are 
considered adequate to allow for the characterization of the drug’s PK after oral dosing. 
Furthermore, the chosen PK sample collection for CBP-307 is anticipated to be sufficient to 
allow reasonable estimation of t1/2 during the terminal elimination phase.  
3.3. 
Selection of Doses in the Study 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To 
carefully monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 
doses will be up-titrated as follows: subjects will receive a starting dose of 0.05 mg CBP-307 
on Day 1 followed by an up-titrated dose of 0.1 mg on Day 2 and a dose of 0.2 mg on 
Days 3 to 6. Prior clinical experience with CBP-307 has not demonstrated clinically 
significant abnormalities in laboratory test results in the majority of subjects or a dose-
response relationship for safety based on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the 
characteristics of the study design with the safety of healthy subjects. Testing of CBP-307 at 
substantial multiples of the anticipated maximum therapeutic exposure is not clinically 
warranted due to the known safety and tolerability profile of CBP-307.  


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Further details are provided in the IB.1 
4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the screening visit unless otherwise 
stated: 
1. Males or females, of any race, between 18 and 60 years of age, inclusive. 
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive. 
3. In good health, determined by no clinically significant findings from medical history, 
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) at screening and 
confirmed at check-in as assessed by the investigator (or designee). 
4. Females will not be pregnant or lactating, and females of childbearing potential and 
males will agree to use contraception as detailed in Appendix 4. Negative pregnancy 
test for females of childbearing potential at screening (blood test) and check-in (urine 
test); 
5. Supine diastolic blood pressure between 60 and 90 mmHg and systolic blood pressure 
between 90 and 140 mmHg (inclusive) at screening on a single measurement 
(confirmed by a single repeat, if necessary) following at least 5 minutes of rest; 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
a. Normal sinus rhythm (HR between 60 bpm and 100 bpm inclusive); 
b. QTcF interval ≤450 msec for males and ≤470 msec for females; 
c. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
d. PR interval ≤200 msec. 
7. Has serum potassium, calcium, and magnesium levels within the normal reference 
range at screening, as judged by the investigator. 
8. Able to swallow multiple tablets (based on subject’s verbal confirmation). 
9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 
4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
screening visit unless otherwise stated: 
1. Subject is mentally or legally incapacitated or has had significant history of recent 
mental health issues requiring medication and/or hospitalization at the time of the 
screening visit or expected during the conduct of the study. 


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2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, 
hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the 
investigator (or designee). Note: Childhood asthma that is considered recovered or 
seasonal allergies that are not currently active or requiring treatment are allowed. 
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, unless approved by the investigator (or designee). 
4. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, 
related compounds, or inactive ingredients. 
5. History of significant multiple and/or severe allergies (eg, latex allergy, band-aids, 
adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant 
intolerability to prescription or nonprescription drugs. 
6. History of stomach or intestinal surgery or resection that would potentially alter 
absorption and/or excretion of orally administered drugs within 6 months prior to the 
first dose of study drug (uncomplicated appendectomy and hernia repair will be 
allowed). 
7. History or presence of: 
a. Hypokalemia, in the opinion of the investigator (or designee); 
b. Risk factors for Torsades de Pointes (eg, heart failure, cardiomyopathy, or 
family history of Long QT Syndrome); 
c. Sick sinus syndrome, second, or third degree atrioventricular block, 
myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged 
QT interval, or conduction abnormalities; 
d. Repeated or frequent syncope or vasovagal episodes; 
e. Hypertension, angina, bradycardia, or severe peripheral arterial circulatory 
disorders. 
8. Clinically significant abnormalities (as judged by the investigator in laboratory tests 
results [out-of-range results confirmed on repeat]), including but not limited to the 
following parameters: 
a. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or 
total bilirubin greater than 1.5 × upper limit of normal; 
b. hemoglobin <10 g/dL, WBC <3.0 ×109/L, neutrophils <1.5 ×109/L, 
lymphocytes <0.8 ×109/L and platelets <100 ×109/L or >1200 × 109/L; 
9. History or evidence of alcoholism or drug/chemical abuse within 2 years prior to 
check-in. 
10. Alcohol consumption of >10 units per week for males and females. One unit of 
alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill 
(25 mL) of spirits. 
11. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) 
at screening or check-in.  


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12. Positive hepatitis panel, positive syphilis test, and/or positive human 
immunodeficiency virus test (Appendix 2).  
13. Participation in a clinical study involving administration of an investigational drug 
(new chemical entity) in the past 28 days prior to the first dose of study treatment on 
Day 1. The 28-day window will be derived from the date of the last blood collection 
or dosing, whichever is later, in the previous study to Day 1 of the current study. 
14. Participation in a previous clinical study where subjects received CBP-307. 
15. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 
28 days prior to first dose of study treatment on Day 1. 
16. Use or intend to use any prescription medications/products within 14 days prior to 
first dose of study drug (Day 1) and throughout the study, unless deemed acceptable 
by the investigator (or designee). Note: For females only, the use hormonal 
contraception, hormone replacement therapy or oral, implantable, transdermal, 
injectable, or intrauterine hormonal contraceptives within 14 days prior to Day 1 is 
not acceptable, except for Mirena®. 
17. Use or intend to use any drugs known to be significant inhibitors or inducers of CYP 
enzymes and/or P-gp, including St. John’s Wort, for days prior to the first dose of 
study drug and throughout the study. Appropriate sources will be consulted by the 
investigator or designee to confirm the lack of PK/PD interaction with the study drug. 
18. Use or intend to use slow-release medications/products considered to still be active 
within 14 days prior to check-in, unless deemed acceptable by the investigator (or 
designee). 
19. Use or intend to use any nonprescription medications/products including antacids, 
vitamins (especially those containing magnesium, aluminum, iron, or zinc), minerals, 
and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to 
check-in, unless deemed acceptable by the investigator (or designee). 
20. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or 
positive cotinine at screening or check-in.  
21. Has been on a diet incompatible with the on-study diet (including an extreme diet 
which resulted in a significant weight change for whatever reason), in the opinion of 
the investigator, within the 28 days prior to the first dose of study treatment, and 
throughout the study. 
22. Consumption of caffeine/xanthine-containing foods or beverages within 48 hours 
prior to check-in until discharge. 
23. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages 
within 7 days prior to check-in. 
24. Receipt of blood products within 2 months prior to check-in. 
25. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to 
screening, or platelets from 6 weeks prior to screening. 
26. Poor peripheral venous access. 


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27. Subjects who, in the opinion of the investigator (or designee), should not participate 
in this study. 
4.3. 
Subject Number and Identification 
Subjects will have a unique identification number used at screening. Eligible subjects will be 
assigned a subject number prior to the first dosing occasion. Assignment of subject numbers 
will be in ascending order and no numbers will be omitted (eg, Subjects 0101, 0102, 0103). 
The screening number will be used on all safety samples throughout the study. Replacement 
subjects (Section 4.4) will be assigned a subject number corresponding to the number of the 
subject he/she is replacing plus 1000 (eg, Subject 1101 replaces Subject 0101). 
Subjects will be identified by screening identification number or subject number only on all 
study documentation. A list identifying the subjects by subject number will be kept in the site 
master file. 
4.4. 
Subject Withdrawal and Replacement 
A subject is free to withdraw their informed consent from the study at any time or they may 
be withdrawn at any time at the discretion of the investigator or the sponsor for safety, 
behavioral, or the inability of the subject to comply with the protocol-required visits or 
procedures. In addition, a subject will be withdrawn from dosing if any of the following 
criteria are met: 
• change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the investigator (or designee) 
• noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the investigator (or designee) 
• any clinically relevant sign or symptom that, in the opinion of the investigator (or 
designee), warrants subject withdrawal. 
If a subject is withdrawn from dosing, the sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic case report form (eCRF). If 
a subject is withdrawn from the study, efforts will be made to perform all follow-up 
assessments, if possible (Appendix 6). Other procedures may be performed at the 
investigator’s (or designee’s) and/or sponsor’s discretion. If the subject is in-house, these 
procedures should be performed before the subject is discharged from the clinic. The 
investigator (or designee) may also request that the subject return for an additional follow-up 
visit. All withdrawn subjects will be followed until resolution of all their AEs or until the 
unresolved AEs are judged by the investigator (or designee) to have stabilized. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, effort should be made to document subject outcome, if possible. 
The investigator should inquire about the reason for withdrawal, request the subject to return 
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Subjects who are withdrawn for reasons not related to study treatment may be replaced 
following discussion between the investigator and the sponsor. Subjects withdrawn as a result 
of AEs thought to be related to the study treatment will generally not be replaced. 
4.5. 
Study Termination 
The study may be discontinued at the discretion of the investigator (or designee), sponsor, or 
sponsor’s medical monitor if any of the following criteria are met: 
• investigator decides to terminate the study due to safety concerns such as AEs 
unknown to date (ie, not previously reported in any similar investigational study drug 
trial with respect to their nature, severity, and/or duration) 
• increased frequency, severity, and/or duration of known, anticipated, or previously 
reported AEs (this may also apply to AEs defined at check-in as baseline signs and 
symptoms) 
• medical or ethical reasons affecting the continued performance of the study 
• difficulties in the recruitment of subjects 
• cancelation of drug development 
• sponsor requests for termination (eg, due to financial or management reasons, etc.) 
under the premise to fully protect the safety and rights of subjects  
• health authority or ethics committee (EC) orders the termination of the trial for any 
reason. 
Definition of end-of-treatment and end-of-study  
• end-of-treatment is completion of safety follow-up or withdrawal from the study. 
End-of-study is the last visit by the last subject. 
5. STUDY TREATMENTS 
Study treatments are defined as any investigational product (IP), non-investigational product 
(non-IP), placebo, or medical device intended to be administered to a study subject according 
to the study protocol. 
Note that in several countries, IP and non-IP are referred to as IMP and non-IMP, 
respectively. 
5.1. 
Investigational Products 
The details regarding the storage, preparation, destruction, and administration of each 
treatment shown in Table 3 will be provided in a separate document. Approximately 
64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 
and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and 
each sub-group will be randomized with 16 subjects.  
 


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Table 3: Study Treatments 
Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage Form 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
 
0.05 mg 
0.1 mg 
Not applicable 400 mg 
Not applicable 
Dosage Frequency  
 
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.05 mg 
 
 
1 tablet 
 Group 2A 
 
1 capsule 
1 × 400 mg 
 
 Group 2B 
 
1 capsule 
 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
 
 
 
Group 2A 
 
1 capsule 
 
 
Group 2B 
 
1 capsule 
 
 
Days 3 to 6 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 7 to 15 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 16 Group 1 
 
 
 
1 tablet 
Group 2A 
 
 
 
1 tablet 
Group 2B 
 
 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
electronic 
case report 
form (eCRF). 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigational 
product is to 
be recorded 
on each 
subject's 
eCRF. 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosing Instructions 
 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
Treatments 
will be 
administered 
after the 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximately 
240 mL of 
room 
temperature 
water. 
 
All supplies of the IMP, both bulk and subject-specific, will be stored in accordance with the 
manufacturer’s or pharmacy’s instructions. Until dispensed to the subjects, the study 
treatments will be stored at the study site in a location that is locked with restricted access. 
5.2. 
Study Treatment Administration 
Each dose of study treatment (CBP-307, placebo, or moxifloxacin) will be administered 
orally following an overnight fast of at least 10 hours, with approximately 240 mL of room 
temperature water. Additionally, because food has been shown to alter the PK of CBP-307, 
subjects will be fasted at least 10 hours prior to dose administration and remain fasted for 
4 hours postdose on the days when PK samples are collected. 
Subjects will be dosed in numerical order while sitting or standing but not be permitted to lie 
supine for 2 hours after treatment administration, except as necessitated by the occurrence of 
an AE(s) and/or study procedures. 
5.3. 
Randomization 
This is a double-blind randomized study. Subjects will be randomized to one of the treatment 
sequences before administration of the first dose of study treatment. A randomization list will 
be generated by a statistician using a computer-generated pseudo-random permutation 
procedure. The randomization date is to be documented in the subject’s medical record and 
on the enrollment eCRF. A computer-generated randomization schedule and emergency 
code-break envelopes will be provided to the study site. Randomization details will be 
included in the randomization specification. 


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5.4. 
Blinding 
This is a double-blinded study. The following controls will be employed to maintain the 
double-blind status of the study: 
• The placebo will be identical in appearance to CBP-307 or moxifloxacin. 
• The investigator and other members of staff involved with the study will remain 
blinded to the treatment randomization code during the assembly procedure. 
• Interim bioanalytical data will be provided to Covance Early Clinical Biometrics in a 
blinded manner. 
To maintain the blind, the investigator will be provided with a sealed randomization code for 
each subject, containing coded details of the treatment. These individually sealed envelopes 
will be kept in a limited access area that is accessible 24 hours a day. If, in order to manage 
subject safety or to support dose escalation decisions (in the event of possibly 
treatment-related SAEs or severe AEs), the decision to unblind resides solely with the 
investigator. Whenever possible, and providing it does not interfere with or delay any 
decision in the best interest of the subject, the investigator will discuss the intended 
code-break with the sponsor. If it becomes necessary to break the code during the study, the 
date, time, and reason will be recorded in the subject's source data and on the individual 
envelope and will be witnessed by a second person. 
5.5. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of suitably qualified study site 
staff. 
• Immediately after dose administration, visual inspection of the mouth and hands will 
be performed for each subject. 
• At each dosing occasion, a predose and postdose inventory of IMP will be performed.   
5.6. 
Drug Accountability 
The investigator (or designee) will maintain an accurate record of the receipt of study 
treatments (CBP-307, moxifloxacin, placebo-matched CBP-307, and placebo-matched 
moxifloxacin) received. In addition, an accurate drug disposition record will be kept, 
specifying the amount dispensed to each subject and the date of dispensing. This drug 
accountability record will be available for inspection at any time. At the completion of the 
study, the original drug accountability record will be available for review by the sponsor 
upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused 
assembled unit doses will be retained until the completion of the study. 


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At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the 
study site’s pharmacy (RAH Pharmacy), per the sponsor’s written instructions. If destruction 
is authorized to take place at the study site’s pharmacy, the investigator must ensure that the 
materials are destroyed in compliance with applicable environmental regulations and 
institutional policy. All study drug destructions must be adequately documented. 
6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects will refrain from the use of any prescription or nonprescription medications/products 
during the study until the follow-up visit, unless the investigator (or designee) and/or sponsor 
have given their prior consent. Medications taken within 28 days before study treatment 
administration will be documented as a prior treatment. Treatments taken after study 
treatment administration will be documented as concomitant treatments. 
Paracetamol/acetaminophen (2 g/day for up to 3 consecutive days) is an acceptable 
concomitant medication. The administration of any other concomitant medications during the 
study is prohibited without prior approval of the investigator (or designee), unless its use is 
deemed necessary for the treatment of an AE. Any medication taken by a subject during the 
course of the study and the reason for its use will be documented in the source data.  
Females will refrain from the use of hormone replacement therapy and oral, implantable, 
transdermal, injectable, or intrauterine hormonal contraceptives (with the exception of 
Mirena®) during the study until the follow-up visit (See Appendix 4). 
6.2. 
Diet 
While confined at the study site, subjects will receive a standardized diet at scheduled times 
that do not conflict with other study-related activities. Subjects will be fasted overnight (at 
least 10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be 
allowed from 7 days prior to check-in until follow-up visit on Day 29±2 days. 
Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 19. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge 
on Day 19 and alcohol intake will be limited to a maximum of 2 units/day on all other days, 
whilst not at the study site, from screening to 72 hours prior to the follow-up visit on 
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6.3. 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 
3 months prior to check-in until the follow-up visit. 
6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 29±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 3 months prior to screening, 
plasma from 2 weeks prior to screening, and platelets from 6 weeks prior to screening until 
3 months after the follow-up visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. The order of 
priority for scheduling procedures around a timepoint is (in descending order of priority): 
• dosing 
• continuous ECG extraction window 
• pharmacokinetic blood samples 
• safety assessments  
• any other procedures. 
This study includes a screening period (Day -28 to Day -3), a treatment period (Days -2 to 
19), and a follow-up period (Day 29 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2) 
or baseline (Day -1 predose) will only be considered exclusionary if judged applicable by the 
investigator. For confirmation of enrollment eligibility based on pulse rate, the pulse rate 
assessed by vital signs, rather than the 12-lead ECG, will be used. For all subjects, the 
screening, check-in, or baseline blood pressure, pulse rate, and respiratory rate may be 
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7.1. 
General Assessments 
7.1.1. 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in order 
to study their possible association with subject safety and treatment effectiveness. 
7.1.2. 
Medical History 
At the timepoint specified in Appendix 6, the investigator or designee will collect a complete 
medical and surgical history. Medical history will include information on the subject’s 
concurrent medical conditions and any events occurring prior to the first dose of study 
treatment. All findings will be recorded on the medical history eCRF. 
7.2. 
Electrocardiography Assessments 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording 
Continuous 12-lead digital ECG recording will be performed as specified in Appendix 6. All 
ECG data will be collected using a Holter (or Mortara Surveyor) ECG continuous 12-lead 
digital recorder. The 12-lead Holter (or Mortara Surveyor) ECG equipment will be supplied 
and supported by ERT (eResearch Technology Inc., Philadelphia, PA). The continuous 
12-lead digital ECG data will be stored onto SD memory cards.  
The ECGs to be used in the analyses will be selected by predetermined timepoints as defined 
in Appendix 6 and will be read centrally by ERT (eResearch Technology Inc., Philadelphia, 
PA). The following principles will be followed in ERT’s core laboratory: 
• ECG analysts are blinded to the subject, visit, and treatment allocation. 
• Baseline and on-treatment ECGs for a particular subject will be over-read on the same 
lead and will be analyzed by the same reader. 
The primary analysis lead is lead II. If lead II is not analyzable, then the primary lead of 
analysis will be changed to another lead for the entire subject data set. 
The 12-lead ECGs will be extracted in up to 10 replicates at the predefined timepoints and 
subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 minutes 
after each nominal time. 
7.2.1.1. 
TQT Plus Extraction Technique 
Ten 14-second digital 12-lead ECG tracings will be extracted from the continuous Holter (or 
Mortara Surveyor) recordings using the ‘TQT Plus method’, a computer-assisted and 
statistical process utilized by ERT. The method enables extraction of ECGs with the lowest 
HR variability and noise within the protocol-specified extraction time window (eg, the HR 
and QT changes from beat-to-beat in the range of <10%). At each protocol-specified 
timepoint, 10 ECG replicates will be extracted from a 5-minute “ECG window” (typically, 


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the last 5 minutes of the 15-minute period when the subject is maintained in a supine, quiet 
position). 
7.2.1.2. 
Expert Precision QT Analysis 
Expert precision QT analysis will be performed on all analyzable (non-artifact) beats in the 
10 ECG replicates. Statistical quality control procedures are used to review and assess all 
beats and identify “high” and “low” confidence beats using several criteria, including: 
•
QT or QTc values exceeding or below certain thresholds (biologically unlikely).
•
RR values exceeding or below certain thresholds (biologically unlikely).
•
Rapid changes in QT, QTc, or RR from beat-to-beat.
Measurements of all primary ECG parameters (QT, QTc, RR) in all recorded beats of all 
replicates that are deemed “high confidence” will be performed using COMPAS software. 
All low-confidence beats will be reviewed manually and adjudicated using pass-fail criteria. 
The final QC assessment will be performed by a cardiologist. The beats found acceptable by 
manual review will be included in the analysis. The median QT, QTc, and RR values from 
each extracted replicate will be calculated, and then the mean of all available medians from a 
nominal timepoint will be used as the subject’s reportable value at that timepoint. 
Categorical T-wave morphology analysis and the measurement of PR and QRS interval of the 
ECG (QRS) intervals will be performed manually in 3 of the 10 ECG replicates at each 
timepoint. Each fiducial point (onset of P-wave, onset of Q-wave, offset of S-wave, and 
offset of T-wave) will be electronically marked. 
For T-wave morphology and U-wave presence, treatment-emergent changes will be assessed 
(ie, changes not present at baseline). For each category of T-wave morphology and U-waves, 
the category will be deemed as present if observed in any replicate at the timepoint. For 
baseline, the category will be deemed as present if observed in any replicate from all 
timepoints that constitute baseline. 
7.2.2. 
Safety 12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at 
least 5 minutes at the times indicated in the Schedule of Assessments in Appendix 6. Single 
12-lead ECGs will be repeated twice, and an average taken of the 3 readings, if either of the 
following criteria applies:
•
QT interval corrected for HR using Fridericia’s method (QTcF) is >500 ms
•
QTcF change from the baseline (predose) is >60 ms.
Additional 12-lead ECGs may be performed at other times if judged to be clinically 
appropriate or if the ongoing review of the data suggests a more detailed assessment of ECGs 
is required. The investigator (or designee) will perform a clinical assessment of each 12-lead 
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7.2.3. 
Cardiac Telemetry Monitoring 
Subjects will be monitored via cardiac telemetry from approximately 1 hour prior to dose 
administration and until approximately 12 hours postdose on Days 1, 2, 3, and 7 (up-titration 
days; as described in Appendix 6). Based on the emerging safety data from the study, the 
duration of the telemetry may be extended if necessary. 
The start and stop date and time of the telemetry monitoring will be recorded in the eCRFs. 
Clinically significant abnormalities noted from telemetry monitoring will be confirmed by 
12-lead ECG if necessary, then after confirming, the abnormities will be reported as AEs in 
the eCRF. 
7.3. 
Pharmacokinetic Assessments  
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples (approximately 1 × 3 mL for CBP-307 and moxifloxacin assays) will be 
collected by venipuncture or cannulation at the times indicated in the Schedule of 
Assessments in Appendix 6. Procedures for collection, processing, and shipping of PK blood 
samples will be detailed in a separate document.  
7.3.2. 
Analytical Methodology 
Plasma concentrations of CBP-307 and moxifloxacin will be determined using a validated 
analytical procedure. Specifics of the analytical method will be provided in a separate 
document.  
7.4. 
Safety and Tolerability Assessments 
7.4.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF until the 
follow-up visit. Subjects will be observed for any signs or symptoms and asked about their 
condition by open questioning, such as “How have you been feeling since you were last 
asked?”, at least once each day while resident at the study site and each study visit. Subjects 
will also be encouraged to spontaneously report AEs occurring at any other time during the 
study. 
All nonserious AEs, whether reported by the subject voluntarily or upon questioning, or 
noted on physical examination, will be recorded from initiation of placebo administration to 
all subjects (Day -1) until study completion. If AEs that occur in the screening prior to 
placebo administration to all subjects (Day -1) are considered to be related to the study 
procedure, they should be also collected. Serious AEs will be recorded from the time the 
subject signs the ICF until study completion. The nature, time of onset, duration, and severity 
will be documented, together with an investigator’s (or designee’s) opinion of the 
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Adverse events recorded during the course of the study will be followed up, where possible, 
to resolution or until the unresolved AEs are judged by the investigator (or designee) to have 
stabilized. This will be completed at the investigator’s (or designee’s) discretion. 
7.4.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations at the times 
indicated in the Schedule of Assessments in Appendix 6. Clinical laboratory evaluations are 
listed in Appendix 2. 
A serum qualitative pregnancy or urine test (females only) and follicle-stimulating hormone 
test (postmenopausal females only) will be performed at the timepoints specified in 
Appendix 6. A positive urine pregnancy test will be confirmed with a serum pregnancy test. 
All pregnancies should be reported as specified in Appendix 1. 
Additional clinical laboratory evaluations will be performed at other times if judged to be 
clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of clinical laboratory safety evaluations is required. At the discretion of the 
investigator, clinically significant clinical laboratory assessments may be confirmed by repeat 
sampling. If the clinical significance is confirmed, subjects will be excluded from 
participation or, if already included, will be followed until normalization of the test result or 
for as long as the investigator considers necessary. 
Subjects will be asked to provide urine samples for drugs of abuse screen and cotinine test, 
and will undergo an alcohol breath test at the times indicated in the Schedule of Assessments 
in Appendix 6. For all female subjects, a pregnancy test will be performed at the times 
indicated in the Schedule of Assessments in Appendix 6.   
An investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.4.3. 
Vital Signs 
Supine blood pressure, supine pulse rate, respiratory rate, and tympanic temperature will be 
assessed at the times indicated in the Schedule of Assessments in Appendix 6. Vital signs 
may also be performed at other times if judged to be clinically appropriate or if the ongoing 
review of the data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly. For all subjects, the screening, check-in, or 
baseline blood pressure, pulse rate, and respiratory rate may be repeated after 5 to 10 minutes 
if the initial reading is believed to be atypical for the subject. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
7.4.4. 
Physical Examination 
A full physical examination will be performed at the timepoints specified in the Schedule of 
Assessments in Appendix 6. Physical examinations include general appearance, head, eyes, 


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ears, nose, and throat, neck (including thyroid and nodes), cardiovascular, respiratory, 
gastrointestinal, renal, neurological, musculoskeletal, skin, and others. 
Height, weight, and body mass index will be assessed at screening. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Sample Size for Primary Analysis: 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-msec QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-307 
in the study. This power is estimated approximately using a 2-sample t-test. The calculation 
assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 3 msec and a 
standard deviation (SD) of the ΔQTcF of 8 msec for both CBP-307 and placebo treatment 
groups. Note that this calculation is conservative, since it does not take into account any gain 
in precision due to the use of all data of each subject with the help of a linear mixed-effects 
model. The concentration-QTc analysis method is supported by Darpo et al 20153 and 
Ferber et al, 2015,4 and consistent with the experiences from 25 recent TQT studies. 
Sample Size Considerations for Assay Sensitivity: 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that the 
ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 msec (ie, the lower bound of the 
2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 msec). In a similarly 
designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the standard 
error (SE) for the prediction of the QT effect of moxifloxacin based on the exposure-response 
analysis was 1.24 msec. The within-subject SD of ΔQTcF in the referred study was 5.4 msec 
based on the by-timepoint analysis. If the effect of moxifloxacin is assumed to be 10 msec, 
the SE of 1.24 msec corresponds to an effect size of (10-5)/(1.24×sqrt[24])=0.82, where the 
effect size is the effect assumed under the alternative hypothesis divided by the SD of the test 
variable. This value should be compared to the effect size of 0.64 required to guarantee a 
power of at least 95% in a paired t-test situation with a sample size of 28 evaluable subjects. 
In other words, based on this calculation, a power of at least 95% will be obtained as long as 
the variability of the ΔQTcF, as measured by its within-subject SD from the by-timepoint 
analysis, does not exceed 6.9 msec (ie, 128% [= 0.82/0.64] of the 5.4 msec observed in the 
referred study assuming the ratio of effective sizes is consistent with inverse ratio of 
within-subject SD). The number also agrees with recent recommendations of the FDA, which 
propose at least 20 subjects.5 


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8.2. 
Analysis Populations 
8.2.1. 
Cardiodynamic Population 
The QT/QTc population will include all subjects in the safety population with measurements 
at baseline as well as on-treatment with at least 1 postdose timepoint with a valid ΔQTcF 
value. The QT/QTc population will be used for the by-timepoint and categorical analyses of 
the cardiodynamic ECG parameters. 
The PK/QTc population will include all subjects who are in both the QT/QTc and PK 
populations with at least 1 pair of postdose PK and ∆QTcF data from the same timepoint as 
well as subjects in the QT/QTc population who received placebo. The PK/QTc population 
will be used for the concentration-QTc analysis and assay sensitivity. PK/QTc population 
will be defined for CBP-307, and for moxifloxacin.  
The as-treated principle will be applied to all analysis populations mentioned below. 
8.2.2. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of investigational 
product and have evaluable PK data of any of the analytes (CBP-307 and moxifloxacin). A 
subject will be excluded from the PK summary statistics and statistical analysis if the subject 
has an AE of vomiting that occurs at or before 2 times median time to maximum 
concentration.  
8.2.3. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of investigational 
product drug (therapeutic and supratherapeutic doses of CBP-307, moxifloxacin, or placebo). 
8.3. 
Cardiodynamic ECG Analyses 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus 
placebo in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1, baseline will be Day 16, on 
which subjects are administered placebo. For placebo-correction in this group, 
placebo values will be derived from Day 15 on which subjects are administered 
placebo, and baseline will be obtained on Day -1. 
• Group 2B: For moxifloxacin administered on Day 16, baseline will be Day 1, on 
which subjects are administered placebo. For the placebo-correction in this group, 
Day -1 values will be used as placebo (no treatment) and baseline will be obtained on 
Day 15. 


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Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as 
the dependent variable, time-matched concentrations of CBP-307 as the exploratory variate 
(0 for placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on 
Days 1, 6, and 15 categorical) as fixed effects, and a random intercept and slope per subject.6  
The degrees of freedom estimates will be determined by the Kenward-Roger method. From 
the model, the slope (ie, the regression parameter for the CBP-307 concentration) and the 
treatment effect-specific intercept will be estimated together with 2-sided 90% CI. The 
estimates for the time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-time point analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 6, 
and 15, and Days 1 and 16 for active versus placebo and moxifloxacin versus placebo, 
respectively. All times are relative to the time of dosing on that day which is considered the 
first dose for the assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the 
first dose of study treatment is on Day 1. 
The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in 
the active drug groups on each of Days 6 and 15 will be determined, respectively. The 
predicted effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF 
(ΔΔQTcF) (ie, slope estimate × concentration + treatment effect-specific intercept) at this 
geometric mean Cmax will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the 
observed ΔQTcF values adjusted by population time effect estimated from the model will be 
used. These individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed 
individual ΔQTcFi,k for subject i administered with active drug or placebo at timepoint k 
minus the estimated population mean placebo effect at timepoint k (ie, time effect). A decile 
plot, ie, plot of the deciles of observed concentrations and the mean placebo-adjusted ΔQTcF 
(ΔΔQTcF) and 90% CI at the median concentration within each decile will be given. The 
regression line presenting the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a 
linear model and visualize the concentration-response relationship. The placebo-adjusted 
ΔQTcFi,j equals the individual ΔQTcFi,j for subject i administered with CBP-307 at timepoint 
j minus the estimation of time at timepoint j (ie, time effect). Additional exploratory analyses 
(via graphical displays and/or model fitting) will include accounting for a delayed effect 
(hysteresis) and the justification for the choice of PD model (linear versus nonlinear) as 
follows. 
Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the 
observed geometric mean Cmax on Days 6 and 15 as well as clinically relevant plasma levels 
is below 10 msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax 


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<10 msec), it can be concluded that CBP-307 does not cause clinically concerning QT 
prolongation within the observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 6 and 15; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on 
Days 6 and 15; and if the difference (delay) between the time to reach the peak QTc effect 
(ΔΔQTcF) and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of 
more than 1 hour is observed in a consistent way for the active dose groups on Days 6 and 15, 
other concentration-QTc models, such as a model with an effect compartment, may be 
explored. With the provision stated above, hysteresis will be assumed if this curve shows a 
counterclockwise loop. A significant treatment effect-specific intercept may also be 
indicative of hysteresis or model misspecification, if it cannot be explained by a nonlinear 
relationship. 
Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 
time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a 
scatter plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI 
and a linear regression line will also be provided to check the assumption of a linear 
concentration-QTc relationship. If there is an indication that a linear model is inappropriate, 
additional models may be fitted, such as an E-max model. The concentration-QTc analysis 
will then be repeated for the model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of 
moxifloxacin data. If the slope of the concentration-QTc (change-from-baseline QTcF) for 
moxifloxacin is statistically significant at 10% level for 2-sided test and the lower bound of 
the 2-sided 90% CI of the predicted effect is above 5 msec at the observed geometric mean 
Cmax of the 400-mg dose, assay sensitivity will be deemed to have been demonstrated. 
By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 6, and 15: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 15, and corresponding placebo), and 


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time-by-treatment interaction as fixed effects. An unstructured covariance matrix will be 
specified for the repeated measures at postdose timepoints within subjects. If the model with 
unstructured covariance matrix fails to converge, other covariance matrices such as 
compound symmetry and autoregressive will be considered. From this analysis, the LS mean, 
SE, and 2-sided 90% CIs will be calculated for the contrast “CBP-307 versus placebo” for 
each day of Days 1, 6, and 15 at each postbaseline timepoint on Days 1, 6, and Day 15, 
respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo 
at postbaseline timepoints on Day 1 and Day 16. A linear mixed-effects model will be used 
with ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 
16: categorical), treatment (moxifloxacin and placebo), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. An unstructured 
covariance matrix will be specified for the repeated measures at postbaseline timepoints for 
subject within visit. The model will also include a subject-specific random effect. If the 
model with an unstructured covariance matrix fails to converge, other covariance matrices, 
such as compound symmetry or autoregressive, will be considered. From this analysis, the LS 
mean, SE, and 2-sided 90% CIs will be calculated for the contrast “moxifloxacin versus 
placebo” at each postbaseline timepoint, respectively. 
For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline 
postdose (ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as 
described for QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both 
change-from-baseline and placebo-corrected change-from-baseline values will be listed in the 
tables and graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will 
be summarized in frequency tables with counts (percentages) for both the number of subjects 
and the number of timepoints. For categorical outliers, the number (percentage) of subjects as 
well as timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 
and ≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline 
>25% to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR 
>100 bpm will be determined. For T-wave morphology and U-wave presence, the analyses 
will be focused on change from baseline (ie, treatment-emergent changes). 
8.4. 
Pharmacokinetic Analyses 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, SD, median, minimum, 
maximum geometric mean, and geometric coefficient of variation) separately by group. 
Individual and mean plasma CBP-307 and moxifloxacin concentration versus time data will 
be tabulated and plotted by dose level. Graphical displays of PK data may be provided as 
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For each subject, the following PK parameters will be calculated, whenever possible, based 
on the plasma concentration for CBP-307 and moxifloxacin, according to the model 
independent approach: 
• Cmax 
• tmax 
• AUC0-24  
• AUCinf 
• apparent terminal elimination rate constant (λZ) 
• t1/2  
• apparent total clearance (CL/F) 
• apparent volume of distribution during the terminal phase (Vz/F)  
• Accumulation ratio (Rac) for Cmax (Rac[Cmax]) and Rac(AUC0-24), calculated as Day 15 
Cmax/Day 7 Cmax and Day 15 AUC0-24/Day 7 AUC0-24, respectively. 
Pharmacokinetic calculations will be performed, if appropriate, using commercial software 
such as Phoenix® WinNonlin® (Version 8.1 or higher). 
Other parameters may be added as appropriate. 
Pharmacokinetic analysis will use actual times as recorded on the eCRF. Other data handling 
procedures will be detailed in the Statistical Analysis Plan. 
8.5. 
Safety Analysis 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed.   
8.6. 
Interim Analysis 
No interim analyses are planned for this study.  
9. REFERENCES 
1. Suzhou Connect. CBP-307 – Investigator’s Brochure. (Version 6.0). December 2020. 
2. Avelox [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016. 


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3. Darpo B, Benson C, Dota C, et al. Results from the IQ-CSRC prospective study support 
replacement of the thorough QT study by QT assessment in the early clinical phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
4. Ferber G, M Zhou, B Darpo. Detection of QTc effects in small studies--implications for 
replacing the thorough QT study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
5. Huang DP, Chen J, Dang Q, et al. Assay sensitivity in “Hybrid thorough QT/QTc (TQT)” 
study. Journal of Biopharmaceutical Statistics. 2019;29(2):378-384. 
6. Garnett C, Bonate PL, Dang Q , et al. Scientific white paper on concentration-QTc 
modeling. [Published correction appears in J Pharmacokinet Pharmacodyn. 
2018;45(3):399]. J Pharmacokinet Pharmacodyn. 2018;45(3):383-397. 
7. Tornøe CW, Garnett CE, Wang Y, et al. Creation of a knowledge management system for 
QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042. 
8. Cleveland WS. Robust Locally Weighted Regression and Smoothing Scatter Plots. 
J Amer Statist Assoc. 1979;74(368):829-36. 
9. Hurvich CM, Simonoff JS, Tsai CL. Smoothing parameter selection in nonparametric 
regression using an improved Akaike information criterion. J Roy Statist Soc Ser B Stat 
Methodol. 1998;60(2):27-193. 
 
 


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10. APPENDICES 


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Appendix 1: Adverse Event Reporting 
Definitions 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a study treatment, whether or not related to the study 
treatment. This includes any newly occurring event or previous condition that had increased 
in severity or frequency since the administration of study medication.  
Examples of AEs include: 
• Symptoms described by the subject, or signs observed by the investigator, and 
• Abnormal findings (involving clinically significant abnormal laboratory tests, ECG, 
etc.)  
• Exacerbation of previous condition, including increased incidence and/or severity. 
Note: Regarding decreased lymphocyte count in peripheral blood in this study, please report 
them as follows: 
• Since a decreased lymphocyte count in peripheral blood is due to the mechanism of 
action of the drug, it is not to be reported as an AE. However, clinical diagnosis 
related to a decreased lymphocyte count in peripheral blood indicates AE reporting (if 
no diagnosis is available, it is required to report related clinical symptoms or signs). 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs. All AEs will 
be recorded in the medical records and eCRFs. The investigator (or designee) is to record in 
detail any AE that occurred to the subject, including: AE diagnosis whenever possible, or 
signs, symptoms, the start date and time of occurrence, the stop date and time of occurrence, 
seriousness (ie, whether it is an SAE), severity of AEs, causality assessment, actions taken on 
the investigational product, other actions (eg, medications/treatments given), and outcomes of 
AEs.  
Assessment of Severity 
The investigator will be asked to provide an assessment of the severity of the AE using the 
following categories:  
• Mild: Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily 
living. 
• Moderate: Usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 


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• Severe: Interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
Relationship to Study Treatment 
The investigator (or designee) will make a determination of the relationship of the AE to the 
study treatment using a 4-category system according to the following guidelines: 
• Not Related: The AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions. 
• Unlikely Related: The temporal association between the AE and the drug is such that 
the drug is not likely to have any reasonable association with the AE. 
• Possibly Related: The AE follows a reasonable temporal sequence from the time of 
drug administration but could have been produced by the subject’s clinical state or the 
study procedures/conditions. 
• Related: The AE follows a reasonable temporal sequence from the administration of 
the drug, abates upon discontinuation of the drug, follows a known or hypothesized 
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced.  
Follow-up of Adverse Events 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject 
who has an ongoing AE that is possibly related or related to the IMP or study procedures at 
the follow-up visit will be followed up, where possible, until resolution or until the 
unresolved AE is judged by the investigator (or designee) to have stabilized. This will be 
completed at the investigator’s (or designee’s) discretion. Any subject who has an ongoing 
AE that is not related or unlikely related to the IMP or study procedures at the follow-up visit 
can be closed out as ongoing at the investigator’s discretion.  
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
For marketed medicinal products, a response to a drug that is noxious and unintended and 
which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases 
or modification of physiological function is to be considered an adverse drug reaction. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, IB for an unapproved 
IMP). 
Serious Adverse Events 
All SAEs will be collected after subjects sign the informed consent form and throughout the 
entire study, ie, until the end-of-study as specified in the protocol (or at early termination). 


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An SAE is defined as any untoward medical occurrence that at any dose either: 
• results in death 
• is life-threatening 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
• results in a congenital anomaly/birth defect 
• results in an important medical event (see below). 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Instances of death or congenital abnormality, if brought to the attention of the investigator at 
any time after cessation of the study treatment and considered by the investigator to be 
possibly related to the study treatment, will be reported to the sponsor (or designee). 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalization 
Adverse events requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the subject has been detained (usually involving an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate at the study site. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered as serious. 
Hospitalization for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a clinical assessment form and 
added to the eCRF. If anything untoward is reported during the procedure, this must be 
reported as an AE and either ‘serious’ or ‘nonserious’ attributed according to the usual 
criteria. 
Serious Adverse Event Reporting 
The investigator will complete an SAE report form and forward it by facsimile or email to 
Covance APAC Drug Safety and the sponsor immediately (within 24 hours) upon becoming 
aware of an SAE. 


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All SAEs must be reported immediately (within 24 hours of discovery) to: +61-2-8879-2000 
SAE Reporting email: SAEIntake@covance.com (preferred method) 
Covance Safety SAE Reporting Fax Number: 61-2-6100-9788 or 1800-882-203 (toll free) 
 
The responsibilities of Covance APAC Drug Safety include the following: 
• Prepare an AE reporting plan prior to the start of the study. Where this plan differs 
from the applicable study site standard operating procedure on SAE reporting, the 
safety management plan will always take precedence. 
• Receive and review SAE report forms from the study site and inform the sponsor of 
the SAE within 1 working day of the initial notification to Covance APAC Drug 
Safety who will delete any information from the SAE report forms that may identify 
the subject. 
• Write case narratives and enter the case into Covance’s safety database as defined in 
the AE reporting plan. 
• Produce appropriate reports of all suspected unexpected serious adverse reactions and 
forward them to the EC, Medicines and Healthcare Products Regulatory Agency, 
principal investigator, and the sponsor within the timeframes stipulated in the Clinical 
Trials Directive Guideline (ENTR/CT 3).  
The responsibility for reporting SAEs will be transferred to the sponsor 28 days after the end 
of the study. 
For SAEs, the active reporting period to sponsor or its designated representative begins from 
the time that the subject provides informed consent through to the last subject visit.  
Nonserious AEs should be collected from the time the subject has taken the placebo dose on 
Day -1 through the last subject visit. If AEs that occur in the screening prior to the placebo 
administration to all subjects on Day -1 are considered to be related to the study procedure, 
they should be also collected.  
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, the 
sponsor should be notified within 24 hours of investigator awareness of the event. This time 
frame also applies to additional new information (follow-up) on previously forwarded SAE 
reports as well as to the initial and follow-up reporting of exposure during pregnancy.  
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.  


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For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the time frames for reporting as specified above. In addition, an investigator 
may be requested by the sponsor to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured on 
the AE eCRF. In general, this will include a description of the AE in sufficient detail to allow 
for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to the sponsor 
or its designated representative. 
Pregnancy 
Pregnancy (maternal or paternal exposure to study treatment) does not meet the definition of 
an AE. However, to fulfill regulatory requirements any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus. 
If the female subject becomes pregnant during the clinical trial and has not yet been dosed 
with study treatment, she must be withdrawn from the study. If the female subject becomes 
pregnant during the clinical trial and has been dosed, she must discontinue treatment 
immediately but may remain on study for safety evaluations. If the partner of a male subject 
becomes pregnant during the clinical trial, the subject can continue the clinical trial.  
For pregnancy of female subjects or partners of the male subjects during this study, 
investigators should report to the sponsor or designee in a pregnancy report form within 
24 hours after investigator awareness and report to the EC in time as per local requirement.  
The investigator will follow up on pregnancy outcomes, until not less than 12 months after 
birth, unless otherwise justified, and will report the outcome to the sponsor and ethics 
committee.  
If any adverse pregnancy outcome (eg, the outcome of the pregnancy is stillbirth, 
spontaneous abortion, or fetal malformations), it should be considered as an SAE and be 
reported in accordance with SAE reporting requirements. 
 
 


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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate  
Magnesium 
Potassium  
Sodium  
Total bilirubin 
Total protein 
Urea 
Uric acid 
Hematocrit  
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell count 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
 
Blood 
Glucose 
Ketones 
Leukocyte esterase  
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination  (if 
indicated by dipstick) 
Serology: 
Drug screen: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency (HIV-1 
and HIV-2) antibodies and p24 
antigen 
Syphilis 
Including but not limited to:  
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol 
Tricyclic antidepressants 
Cotinine test 
Follicle-stimulating hormone 
(postmenopausal females only) 
Serum pregnancy test (human 
chorionic gonadotropin)b 
Urine pregnancy testb  
Other Tests 
Low density lipoprotein cholesterol 
High-density lipoprotein 
cholesterol 
Triglycerides 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated.  
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the 
follow-up visit (on Day 29±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  


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Appendix 3: Total Blood Volume 
The following blood volumes will be withdrawn for each subject. 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
41 
328 
Total: 
390.5 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed 500 mL. 


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Appendix 4: Contraception Guidance 
Definitions 
Women of Childbearing Potential: premenopausal females who are anatomically and 
physiologically capable of becoming pregnant following menarche. 
Women of Nonchildbearing Potential:  
1. Surgically sterile: females who are permanently sterile via hysterectomy, 
bilateral salpingectomy, and/or bilateral oophorectomy by reported medical 
history and/or medical records. Surgical sterilization to have occurred a minimum 
of 6 weeks, or at the investigator’s discretion, prior to screening. 
2. Postmenopausal: females at least 45 years of age with amenorrhea for 12 months 
without an alternative medical reason with confirmatory follicle-stimulating 
hormone (FSH) levels of ≥40 mIU/mL. The amenorrhea should not be induced by 
a medical condition such as anorexia nervosa, hypothyroid disease or polycystic 
ovarian disease, or by extreme exercise. It should not be due to concomitant 
medications that may have induced the amenorrhea such as oral contraceptives, 
hormones, gonadotropin-releasing hormones, anti-estrogens, or selective estrogen 
receptor modulators. Females on hormone replacement therapy with FSH levels 
<40 mIU/mL may be included at the discretion of the investigator.   
Fertile male: a male that is considered fertile after puberty. 
Infertile male: permanently sterile male via bilateral orchiectomy. 
Contraception Guidance 
Female Subjects 
Female subjects who are of nonchildbearing potential will not be required to use 
contraception. Female subjects of childbearing potential must be willing to use 2 methods 
(1 primary and 1 secondary method) of birth control from the time of signing the ICF until 
90 days after the follow-up visit. Primary (non-barrier) methods of contraception include: 
• surgical method performed at least 3 months prior to the screening visit: 
o 
bilateral tubal ligation or bilateral salpingectomy 
o 
Essure® (hysteroscopic bilateral tubal occlusion) with confirmation of 
occlusion of the fallopian tubes 
• non-hormonal intrauterine device or Mirena® (other hormonal intrauterine devices 
will not be allowed) in place for at least 3 months prior to the first dose of the study 
drug 
• vasectomized male partner (sterilization performed at least 90 days prior to the 
screening visit, with verbal confirmation of surgical success, and the sole partner for 
the female subject)  


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Secondary (barrier) methods of contraception include: 
• male condom without spermicide 
• female condom without spermicide 
• cervical cap without spermicide (as prescribed) 
• diaphragm without spermicide (as prescribed). 
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2) until 90 days after the follow-up visit. 
Male Subjects 
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (ie, male condom without spermicide) in addition 
to a second method of acceptable contraception from check-in until 90 days after the 
follow-up visit. Acceptable methods of contraception for female partners include: 
• hormonal injection 
• combined oral contraceptive pill or progestin/progestogen-only pill 
• combined hormonal patch 
• combined hormonal vaginal ring 
• surgical method (bilateral tubal ligation or Essure® [hysteroscopic bilateral tubal 
occlusion])  
• hormonal implant 
• hormonal or non-hormonal intrauterine device 
• cervical cap without spermicide 
• diaphragm without spermicide. 
An acceptable second method of contraception for male subjects is vasectomy that has been 
performed at least 90 days prior to the screening visit with verbal confirmation of surgical 
success. 
For male subjects (even with a history of vasectomy), sexual intercourse with female partners 
who are pregnant or breastfeeding should be avoided unless condoms are used from the time 
of the first dose until 90 days after the follow-up visit. Male subjects are required to refrain 
from donation of sperm from check-in until 90 days after the follow-up visit. 
Sexual Abstinence and Same-sex Relationships 
Subjects who practice true abstinence, because of the subject’s lifestyle choice (ie, the subject 
should not become abstinent just for the purpose of study participation), are exempt from 
contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, symptothermal, 
postovulation methods) and withdrawal are not acceptable methods of contraception. If a 


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subject who is abstinent at the time of signing the ICF becomes sexually active they must 
agree to use contraception as described previously.  
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. If a subject who is in a same-sex relationship at the time of signing the ICF becomes 
engaged in a heterosexual relationship, they must agree to use contraception as described 
previously. 


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Appendix 5: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol, local legal and regulatory 
requirements and with the following: 
• General principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), Guidelines for good clinical practice (GCP) (ICH 1996), and 
the Declaration of Helsinki (World Medical Association 2008).  
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents must be 
submitted to the human research ethics committee (HREC) by the investigator and reviewed 
and approved by the HREC before the study is initiated.  
Any protocol amendments will require EC approval before implementation of changes made 
to the study design, except for changes necessary to eliminate an immediate hazard to study 
subjects.  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents from the 
HREC. All correspondence with HREC should be retained in the investigator file. A copy of 
HREC approval should be forwarded to the sponsor. 
• The investigator will be responsible for the following:  
• Providing written summaries of the status of the study to the EC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the EC.  
• Notifying the EC of SAEs or other significant safety findings as required by EC 
procedures.  
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of ICH guidelines, the EC, and all other applicable local regulations.  
Regulatory Authority  
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency 
in accordance with any applicable country-specific regulatory requirements before the study 
is initiated at a study center in that country. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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Informed Consent 
Prior to starting participation in the study, each subject will be provided with a study-specific 
ICF giving details of the study treatments, procedures, and potential risks of the study. 
Subjects will be instructed that they are free to obtain further information from the 
investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. Subjects will be given an opportunity to ask questions 
about the study prior to providing consent for participation. 
Following the discussion of the study with study site personnel, subjects will sign the ICF in 
the presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. A copy of the ICF will be given to the subject. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
Subject Data Protection 
Subjects will be assigned a unique identifier and will not be identified by name in eCRFs, 
study-related forms, study reports, or any related publications. Subject and investigator 
personal data will be treated in compliance with all applicable laws and regulations. In the 
event the study protocol, study report, or study data are included in a public registry, all 
identifiable information from individual subjects or investigators will be redacted according 
to applicable laws and regulations.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. The subject must also be informed that his/her study-related data 
may be examined by sponsor or contract research organization (CRO) auditors or other 
authorized personnel appointed by the sponsor, by appropriate EC members, and by 
inspectors from regulatory authorities. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the sponsor. 
Data Quality Assurance 
The following data quality steps will be implemented: 
• All relevant subject data relating to the study will be recorded on eCRFs unless 
directly transmitted to the sponsor or designee electronically (eg, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRF.  


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• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
• The investigator must permit study-related monitoring, audits, EC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Predefined agreed risks, monitoring thresholds, 
quality tolerance thresholds, controls, and mitigation plans will be documented in a 
risk management register. Additional details of quality checking to be performed on 
the data may be included in a data management plan.  
• A study monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator in the study site archive for at least 5 years after 
the end of the study unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 Code of Federal 
Regulations Part 11-compliant electronic data capture (EDC) system on an eCRF in a timely 
fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and 
transmitted to the sponsor or designee electronically, will be integrated with the subject’s 
eCRF data in accordance with the data management plan.  
An eCRF must be completed for each enrolled subject who undergoes any screening 
procedures, according to the eCRF completion instructions. The sponsor, or CRO, will 
review the supporting source documentation against the data entered into the eCRFs to verify 
the accuracy of the electronic data. The investigator will ensure that corrections are made to 
the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The investigator will sign and date the eCRF via the EDC system’s electronic signature 
procedure. These signatures will indicate that the investigator reviewed and approved the data 
on the eCRF, data queries, and site notifications. 
Publications 
Publications will be addressed as follows:The results of this study may be published or 
presented at scientific meetings. If this is foreseen, the investigator agrees to submit all 


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Protocol Version 2.0, 10 May 2021  
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manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect 
proprietary information and provide comments. 
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support the publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 


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Appendix 6: Schedule of Assessments 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to clinical 
research unit1 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from clinical 
research unit2  
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height/weight/BMI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematology 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Clinical chemistry  
(including cholesterol panel 
tests) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, 
HBsAb, HBcAb, HBsAg, or 
HCVAb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead safety 
electrocardiogram4,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Cardiac Telemetry 
Monitoring9 
 
 
 
X 
X 
X 
(Day 3) 
 
X 
 (Day 7) 
 
 
 
 
 
 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-
up Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 
3 to 5 
6 
7 to 14 
15 
16 
17 
18 
19 
29±2 
Breath alcohol, urine drug 
toxicology and cotinine  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiodynamic monitoring 
(Holter)/replicate ECG 
extraction5 
 
 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
Pregnancy test6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Follicle -stimulating 
hormone test 
(postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CBP-307/placebo 
administration 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Moxifloxacin/placebo 
administration 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
 
X 
 
X 
X 
 
X 
X 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).  
2. Discharge from unit will occur after the 96-hour PK samples and after completion of safety assessments on Day 19. 
3. Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Days 17, 18, and 19): 
Prior to and 2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Days 17 and 18: Tympanic temperature, 
respiratory rate, and supine pulse rate and blood pressure at approximately the same time each day. Discharge (Day 19): Prior to discharge, supine vital signs (tympanic 
temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 29±2 days): Tympanic temperature, respiratory rate, and supine pulse 
rate and blood pressure. 


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4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days (except for Days 17 and 18) and before discharge on 
Day 19. Postdose safety will be interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 6, 15, and 16. The recording will be started at least 1 hour before 
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1, 
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. When timepoints 
for ECG extraction, safety ECGs, vital signs assessment, and blood draws coincide, procedures will be performed in this order. The ECG effects of CBP-307 will be 
tested on data from Day -1 (baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 15, and 16. 
6. Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 29±2 days). A positive urine 
pregnancy test will be confirmed with a serum pregnancy test. 
7. Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 15, and 16). 
Additional PK samples will be collected at 72 and 96 hours following dosing on Day 15. 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours 
postdose, and ±30 minutes for 12 to 24, 72, and 96 hours postdose. 
9. Subjects will be monitored via cardiac telemetry during the treatment period from approximately 1 hour prior to dose administration and until approximately 12 hours 
postdose on Days 1, 2, 3, and 7 (up-titration days). Based on the emerging safety data from the study, the duration of the telemetry may be extended if necessary. The 
start and stop date and time of the telemetry monitoring will be recorded in the eCRF. 


TITLE PAGE 
Protocol 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, 
Placebo- and Positive-Controlled Study to Investigate the Effects of 
CBP-307 on the QTC Interval in Healthy Subjects 
Protocol Status: Final 
Protocol Date: 18 March 2021 
Protocol Version: 1.0 
Investigational Medicinal Product: CBP-307 
 
Protocol Reference Number: CBP-307AU002 
Covance Study Number: 8463245 
IND Number: 134585 
 
 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu, 215400 
China 
Study Site: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
 
 
Sponsor Signatory: 
Ping Li, MD 
 
Principal Investigator: 
Nicholas Farinola, MBBS 
 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


Protocol 
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Protocol Version 1.0, 18 March 2021  
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SPONSOR APPROVAL 
I have read the protocol and approve it: 
 
 
 
 
 
 
 
Ping Li, MD 
 
Date 
VP, Clinical Development Asia 
DocuSign Envelope ID: 2A773C6E-6A95-48D1-BB16-B61193B173B4
3/19/2021


Protocol 
Covance Study: 8463245 
CONFIDENTIAL 
Protocol Reference: CBP-307AU002 
INVESTIGATOR AGREEMENT 
I have read the protocol and agree to conduct the study as described herein. 
s Farinola, MBBS 
Principal Investigator 
Protocol Version 1.0, 18 March 2021 
Date 
Page 3 of64 


Protocol 
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STUDY IDENTIFICATION 
Sponsor 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Suzhou Connect Biopharmaceuticals, Ltd. 
Science and Technology Park 
East R&D Building, 3rd Floor 
6 Beijing West Road 
Taicang, Jiangsu 215400 
China 
Sponsor’s Study Contact 
Max Meng, BS 
Project Manager 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Tel: +86 0512 5357 7866 
Email: yhmeng@connectpharm.com 
Sponsor’s Medical Contact 
Jane Royalty, MD 
Covance Clinical Research Unit, Inc. 
3402 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 
Tel: 812-474-5015 
Email: jane.royalty@covance.com 
Study Site  
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Principal Investigator 
Nicholas Farinola, MBBS 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Tel: (08) 7088 7900 
Email: nicholas.farinola@sa.gov.au 
Clinical Laboratory  
Australian Clinical Laboratories 
1 Butler Boulevard 
Adelaide Airport  
Adelaide, South Australia 5950 
Australia 


Protocol 
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Protocol Version 1.0, 18 March 2021  
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Bioanalytical Laboratory 
Peter Tapley 
Director, TetraQ 
The University of Queensland 
Level 7, Block 6, RBWH 
Herston, Queensland 4029  
Australia 
Statistician 
Wei Xiao, MS 
Covance Inc. 
3301 Kinsman Boulevard 
Madison, Wisconsin 53704 
USA 


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SYNOPSIS 
Study Title 
A Phase I, Single-center, Randomized, Double-blind, Double-dummy, Placebo- and 
Positive-Controlled Study to Investigate the Effects of CBP-307 on the QTC Interval in 
Healthy Subjects 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the pharmacokinetics (PK) of CBP-307 following administration of 
therapeutic and supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on heart rate (HR), PR and QRS intervals, and T-wave morphology. 
Study Design 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only serious 
adverse events (SAEs) will be reported. After placebo administration to all subjects on 
Day -1, all adverse events (AEs), whether volunteered, elicited, or noted upon physical 
examination, will be recorded throughout the study (ie, from Day -1 until the end of the 
study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 


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Days 1, 2 to 5, 6 to 14, and on Day 15 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• A starting dose of CBP-307 for titration (0.1 mg, Day 1) 
• A therapeutic dose of CBP-307 (0.2 mg, Day 2 to 5) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Day 6 to 14) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 16. Treatment administration will 
occur on Days 1, 2 to 5, 6 to 14, and 15 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic electrocardiogram (ECG) monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 5, 14, 
and 15 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
timepoint. Subjects will return to the study site for a follow-up visit on Day 28±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 5, 14, and 
15. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 5, 
14, and 15; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Subjects will be inactive and in a supine position for at least 
10 minutes prior to and 5 minutes after each cardiodynamic ECG extraction timepoint, which 
will end immediately prior to the PK sampling. When timepoints for ECG extraction, safety 
ECGs, vital sign measurements, and blood draws coincide, procedures will be performed in 
said order. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 5 (therapeutic concentrations versus placebo), and Day 14 


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(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 14, and 15. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit.  
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 58 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
Number of Subjects 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Diagnosis and Main Criteria for Inclusion 
Healthy male and female subjects aged between 18 and 60 years (inclusive) with a body mass 
index between 18.0 and 30.0 kg/m2 (inclusive). 
Investigational Medicinal Products, Dose, and Mode of Administration 
The following treatments will be administered: 
• A starting dose of CBP-307 for titration (0.1 mg, Day 1; oral capsule) 
• A therapeutic dose of CBP-307 (0.2 mg, Day 2 to 5; oral capsule) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Day 6 to 14; oral capsule) 
• Placebo (matched to moxifloxacin, oral tablet and CBP-307; oral capsule) 
• Moxifloxacin (400 mg; oral tablet). 
Duration of Subject Participation in the Study 
Duration of subject participation from the screening visit through follow-up visit will be up to 
approximately 26 days for screening period (Days -28 to -3), 18 days for the in-house 


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treatment period (Days -2 to 16), and 12 ±2 days for follow-up (Day 28±2 days), in total 
approximately 58 days. 
Endpoints 
Electrocardiogram (Cardiodynamic): 
The primary cardiodynamic endpoint is the change-from-baseline QTcF (ΔQTcF). 
The secondary cardiodynamic endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
Pharmacokinetics: 
Blood samples will be collected for the analysis of plasma concentrations of CBP-307. The 
PK parameters of CBP-307 will be calculated using a model independent approach. The 
following PK parameter endpoints will be calculated: maximum observed concentration 
(Cmax), area under the concentration-time curve from time zero extrapolated to infinity 
(AUCinf), area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24), and time of the maximum observed concentration (tmax). Other noncompartmental 
parameters may be reported. 
Safety: 
Adverse events, clinical laboratory evaluations (hematology, clinical chemistry, urinalysis), 
12-lead ECGs, and vital signs measurements. 
Statistical Methods 
Cardiodynamic evaluation: 
The primary analysis will be based on concentration-QTc modeling of the relationship 
between plasma concentrations of CBP-307 and change-from-baseline QTcF (∆QTcF) with 
the intent to exclude an effect of placebo-corrected ΔQTcF (ΔΔQTcF) > 10 msec at clinically 
relevant plasma levels. Placebo-corrected ΔHR, ΔPR, ΔQRS, and ∆QTcF (ΔΔHR, ΔΔPR, 
ΔΔQRS, and ∆∆QTcF) will also be evaluated at each postdosing timepoint ('by-timepoint' 
analysis). An analysis of categorical outliers will be performed for changes in HR, PR, QRS, 
QTcF, T-wave morphology, and U-wave presence. Assay sensitivity will be evaluated by 
concentration-QTc analysis of the effect on ∆ΔQTcF of moxifloxacin using a similar model 
as for the primary analysis. 


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Pharmacokinetics: 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, standard deviation, median, 
minimum, maximum geometric mean, and geometric coefficient of variation) separately by 
cohort. Individual and mean plasma CBP-307 and moxifloxacin concentration versus time 
data will be tabulated and plotted by dose level. Graphical displays of PK data may be 
provided as well.  
Pharmacokinetic/electrocardiography analyses: 
The relationship between CBP-307 plasma concentrations and the change from ∆QTcF will 
be evaluated using a linear mixed-effects modeling approach. 
Safety: 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed. 


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TABLE OF CONTENTS 
TITLE PAGE .............................................................................................................................1 
SPONSOR APPROVAL ...........................................................................................................2 
INVESTIGATOR AGREEMENT.............................................................................................3 
STUDY IDENTIFICATION .....................................................................................................4 
SYNOPSIS .................................................................................................................................6 
TABLE OF CONTENTS .........................................................................................................11 
LIST OF TABLES AND FIGURES........................................................................................14 
LIST OF ABBREVIATIONS ..................................................................................................15 
1. 
INTRODUCTION ...........................................................................................................17 
1.1. 
Disease Background...............................................................................................17 
1.2. 
Overview of CBP-307............................................................................................17 
1.2.1. 
Summary of Clinical Experience .................................................................17 
1.2.1.1. 
Safety .................................................................................................18 
1.2.1.2. 
Pharmacokinetics ...............................................................................20 
1.3. 
Overview of Moxifloxacin .....................................................................................21 
1.4. 
Study Rationale ......................................................................................................21 
1.5. 
Benefit-risk Assessment .........................................................................................22 
2. 
OBJECTIVES AND ENDPOINTS .................................................................................22 
2.1. 
Objectives ..............................................................................................................22 
2.2. 
Endpoints ...............................................................................................................22 
2.2.1. 
Electrocardiogram Endpoints .......................................................................22 
2.2.1.1. 
Primary ...............................................................................................22 
2.2.1.2. 
Secondary ...........................................................................................22 
2.2.2. 
Pharmacokinetic Endpoints .........................................................................23 
2.2.3. 
Safety Endpoints ..........................................................................................23 
3. 
INVESTIGATIONAL PLAN ..........................................................................................23 
3.1. 
Overall Study Design and Plan ..............................................................................23 
3.2. 
Discussion of Study Design ...................................................................................26 
3.3. 
Selection of Doses in the Study .............................................................................26 
4. 
SELECTION OF STUDY POPULATION .....................................................................27 
4.1. 
Inclusion Criteria ...................................................................................................27 
4.2. 
Exclusion Criteria ..................................................................................................27 
4.3. 
Subject Number and Identification ........................................................................30 
4.4. 
Subject Withdrawal and Replacement ...................................................................30 
4.5. 
Study Termination .................................................................................................31 
5. 
STUDY TREATMENTS .................................................................................................31 
5.1. 
Investigational Products .........................................................................................31 
5.2. 
Study Treatment Administration ............................................................................33 


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5.3. 
Randomization .......................................................................................................33 
5.4. 
Blinding..................................................................................................................33 
5.5. 
Treatment Compliance ...........................................................................................34 
5.6. 
Drug Accountability...............................................................................................34 
6. 
CONCOMITANT THERAPIES AND OTHER RESTRICTIONS ................................35 
6.1. 
Concomitant Therapies ..........................................................................................35 
6.2. 
Diet .........................................................................................................................35 
6.3. 
Smoking .................................................................................................................35 
6.4. 
Exercise ..................................................................................................................36 
6.5. 
Blood Donation ......................................................................................................36 
7. 
STUDY ASSESSMENTS AND PROCEDURES ...........................................................36 
7.1. 
General Assessments .............................................................................................36 
7.1.1. 
Demographics ..............................................................................................36 
7.1.2. 
Medical History ...........................................................................................37 
7.2. 
Electrocardiography Assessments .........................................................................37 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording ......................................37 
7.2.1.1. 
TQT Plus Extraction Technique ........................................................37 
7.2.1.2. 
Expert Precision QT Analysis ............................................................37 
7.2.2. 
Safety 12-lead Electrocardiogram ................................................................38 
7.3. 
Pharmacokinetic Assessments ...............................................................................38 
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing ........................38 
7.3.2. 
Analytical Methodology ..............................................................................39 
7.4. 
Safety and Tolerability Assessments .....................................................................39 
7.4.1. 
Adverse Events ............................................................................................39 
7.4.2. 
Clinical Laboratory Evaluations ..................................................................39 
7.4.3. 
Vital Signs ....................................................................................................40 
7.4.4. 
Physical Examination...................................................................................40 
8. 
SAMPLE SIZE AND DATA ANALYSIS ......................................................................40 
8.1. 
Determination of Sample Size ...............................................................................40 
8.2. 
Analysis Populations ..............................................................................................41 
8.2.1. 
Cardiodynamic Population...........................................................................41 
8.2.2. 
Pharmacokinetic Population ........................................................................41 
8.2.3. 
Safety Population .........................................................................................42 
8.3. 
Cardiodynamic ECG Analyses ..............................................................................42 
8.4. 
Pharmacokinetic Analyses .....................................................................................45 
8.5. 
Safety Analysis ......................................................................................................46 
8.6. 
Interim Analysis .....................................................................................................46 
9. 
REFERENCES ................................................................................................................46 
10. APPENDICES .................................................................................................................47 


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Appendix 1: Adverse Event Reporting ..............................................................................48 
Appendix 2: Clinical Laboratory Evaluations ...................................................................53 
Appendix 3: Total Blood Volume ......................................................................................54 
Appendix 4: Contraception Guidance ................................................................................55 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations ............................58 
Appendix 6: Schedule of Assessments ..............................................................................62 
 


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LIST OF TABLES AND FIGURES 
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................20 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) ..............................................................................................21 
Table 3: Study Treatments .................................................................................................32 
Figure 1: Study Schematic .................................................................................................24 
 


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LIST OF ABBREVIATIONS 
Abbreviation Definition 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUCinf 
area under the concentration-time curve from time zero extrapolated to 
infinity 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours 
postdose 
CI 
confidence interval 
CL/F 
apparent total clearance 
Cmax 
maximum observed concentration 
CRO 
contract research organization 
CYP 
cytochrome P450 
Δ 
change-from-baseline 
ΔΔ 
placebo-corrected or placebo-adjusted change-from-baseline 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
HR 
heart rate 
HREC 
human resource ethics committee 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonisation 
IMP 
investigational medicinal product 
IP 
investigational product 
LOESS 
locally estimated scatterplot smoothing 
LS 
least squares 
PK 
pharmacokinetic(s) 
PD 
pharmacodynamic(s) 
QD 
once daily 
QTc 
heart-corrected QT interval 
QTcF 
QT interval corrected for heart rate using Fridericia’s method 
SAE 
serious adverse event 
SD 
standard deviation 


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SE 
standard error 
S1P1 
sphingosine-1-phosphate receptor 1 
TEAE 
treatment-emergent adverse event(s) 
t1/2 
apparent terminal elimination half-life 
tmax 
time of the maximum observed concentration 
TQT 
thorough QT 
Vz/F 
apparent volume of distribution 
WBC 
white blood cell 
λZ 
apparent terminal elimination rate constant 
 
 


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1. INTRODUCTION 
Refer to the investigator’s brochure (IB)1 for detailed information concerning the available 
pharmacology, toxicology, drug metabolism, clinical studies, and adverse event (AE) profile 
of the investigational medicinal product (IMP). 
1.1. 
Disease Background 
Autoimmune diseases are serious disorders that afflict a large portion of the world 
population; most have no cures. Significant advances have been made in the development of 
novel and disease-modifying therapies, but many of these new treatments have significant 
side effects. Treatments are needed that provide better risk-to-benefit profiles than the 
existing therapeutic choices. 
T cells are important immune cells that mediate the development of autoimmune disorders. 
Migration of T cells from lymphoid tissues to the sites of inflammation is central to the 
functions of T cells, and this process is dependent on sphingosine-1-phosphate (S1P) receptor 
1 (S1P1) which is known to ameliorate a variety of autoimmune diseases in animals and 
humans. Down modulation of this receptor, using S1P1 agonists, prevents T cell egress and 
results in a reduced number of circulating lymphocytes, particularly the CD4+- and CD8+-
naïve and central-memory T cell subsets.  
1.2. 
Overview of CBP-307 
CBP-307 is an S1P1 agonist that is being developed as a treatment for autoimmune diseases 
by Suzhou Connect Biopharmaceuticals, Ltd. CBP-307 (1-(2-fluoro-4-(5-(4-isobutylphenyl)-
1,2,4-oxadiazol-3-yl) benzyl) azetidine-3-carboxylic acid hemihydrate) is a potent, selective, 
small-molecule agonist of S1P1 and S1P receptor 5. Cell-based assays have confirmed 
CBP-307 induces internalization of S1P1 from the cell surface. This is consistent with the 
known mechanism of action of other S1P1 agonists, in that they down-modulate S1P1 and 
inhibit lymphocyte egress from lymphoid tissues.  
1.2.1. 
Summary of Clinical Experience 
The Phase 1 development of CBP-307 comprised 2 completed studies in healthy subjects: 
• A single and multiple ascending dose study to evaluate the safety and tolerability of 
CBP-307 including pharmacokinetic (PK), pharmacodynamic (PD), and food-effect 
assessments (Study CBP-307AU001) 
• A single-dose and multiple-dose, and fixed-dose titration study to evaluate the safety 
and tolerability of CBP-307 including PK and PD (Study CBP-307CN001) 
Currently, CBP-307 is being evaluated in 2 Phase 2 studies:  
• Ongoing multicenter study in subjects with moderate to severe ulcerative colitis  
(Study CBP-307CN002) to compare the clinical efficacy by evaluating the clinical 
response to CBP-307 versus placebo and the clinical remission and mucosal healing 


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achieved by CBP-307 versus placebo and to compare the clinical safety and 
tolerability of CBP-307 with those of placebo. 
• Ongoing study in subjects with moderate to severe Crohn’s disease compares clinical 
efficacy by evaluating the clinical response to CBP-307 versus placebo and the 
clinical remission and mucosal healing achieved by CBP-307 versus placebo and to 
compare the clinical safety and tolerability of CBP-307 with those of placebo. 
1.2.1.1. 
Safety 
Study CBP-307AU001 
A total of 44 healthy subjects were enrolled in the study. There were 28 subjects evaluated 
using the single-dose regimen (0.1, 0.25, 0.5, and 2.5 mg CBP-307) of which 21 subjects 
received CBP-307 and 7 subjects received placebo. Another 16 healthy subjects were 
evaluated using the multiple-dose regimen (0.15 and 0.25 mg CBP-307 given once daily 
[QD] for 28 consecutive days) of which 12 subjects received CBP-307 and 4 subjects 
received placebo. 
Overall, no unexpected safety signals were identified and no deaths occurred in this study. 
For the single-dose regiment, no subjects were discontinued due to a treatment-emergent AE 
(TEAE). In the multiple-dose regimen, there were 2 subjects who were discontinued from the 
study (due to increased alanine transaminase and second degree AV block [not considered to 
be clinically significant, as judged by the investigator]). All TEAEs resolved by the end of 
the study. 
In the single-dose regimen groups, TEAEs were reported in 12 of 21 subjects (57.1%) treated 
with CBP-307 and in 3 of 7 subjects (42.8%) treated with placebo. Most (91.7%) of the 
TEAEs in these subjects were mild in severity. The most common TEAEs in the 
CBP-307-treated groups were headache (28.6%); dizziness (19.0%); and bradycardia (9.5%). 
Bradycardia was reported only in 2 subjects receiving the highest (2.5 mg) CBP-307 dose. 
One subject had a serious adverse event (SAE) of bradycardia (associated with transient 
asystole) following a single dose of 2.5 mg CBP-307. 
In the multiple-dose regimen groups, CBP-307 at doses of 0.15 and 0.25 mg QD was 
generally well tolerated over the 28 days of dosing. Treatment-emergent AEs were reported 
in 11 of 12 subjects (91.7%) in the CBP-307 groups and 2 of 4 subjects (50.0%) in the 
placebo groups. Most (83.3%) TEAEs were mild in severity. The most common TEAEs in 
the 2 CBP-307 groups were headache (50.0%), and fatigue, nausea, and musculoskeletal pain 
(16.7% each). The incidences of these TEAEs were similar in both CBP-307-treated groups. 
No SAEs were reported for subjects in the multiple-dose regimen. 
Study CBP-307CN001 
A total of 30 eligible subjects completed 3 CBP-307 dose groups in ascending order of dose 
after randomization (in a ratio of 1:1:1): Group A (0.1 mg), Group B (0.2 mg), and Group C 
(0.3 mg). Each dose group consisted of 10 subjects, including 8 subjects receiving the 
investigational drug and 2 subjects receiving placebo by random assignment. The 
administration started from the dose of 0.1 mg. The subjects in this group received a single 


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dose of CBP-307 or placebo and were followed up for safety and tolerance within the next 
7 days. Then the subjects received 0.1 mg CBP-307 or placebo QD for 14 consecutive days 
and were followed up for safety and tolerance within the next 7 days. Dose escalation did not 
occur until the review of the single-dose regimen safety data from the 6 subjects in the 
previous dose cohort, and the safety data did not meet the termination criteria. The subjects in 
the dose of 0.3 mg received fixed-dose titration regimen, ie, 0.05 mg CBP-307 or placebo QD 
for 3 consecutive days; 0.1 mg CBP-307 or placebo QD for 2 consecutive days; 0.2 mg 
CBP-307 or placebo QD for 2 consecutive days; finally, 0.3 mg CBP-307 or placebo QD for 
14 consecutive days, and the subjects were followed up for safety and tolerance within the 
next 7 days. 
Overall, no unexpected safety signals were identified, and there were no deaths, SAEs, or 
AEs leading to the subject’s early withdrawal from the study after administration of 
CBP-307. In the safety set, a total of 29 subjects (8 in Group A, 100%; 8 in Group B, 100%; 
8 in Group C, 100% and 5 in placebo group, 83.3%) experienced TEAEs. 
During the single-dose period, a total of 14 subjects (5 of 8 in Group A, 62.5%; 6 of 8 in 
Group B, 75%, and 3 of 4 in placebo group, 75%) developed AEs. The incidence of TEAEs 
in Group A was generally similar to the placebo group. Among TEAEs in Group B, the 
incidence of AEs related to abnormalities in investigations was higher than that in placebo 
group, including lymphocyte count decreased (12.5%), white blood cell (WBC) count 
decreased (12.5%), neutrophil count decreased (12.5%), alanine aminotransferase increased 
(25%), and gamma-glutamyltransferase increased (12.5%), and aspartate aminotransferase 
increased (12.5%). Additionally, 1 subject experienced heart rate (HR) decreased (12.5%). 
During dose-titration period, 2 subjects (2 of 8 in Group C, 25%) experienced TEAEs. The 
TEAEs reported in Group C during the titration period included cough (12.5%) and increased 
upper airway secretion (12.5%). There were no TEAEs in the placebo group during this 
period. 
During repeated-dose period, a total of 28 subjects (8 of 8 in Group A, 100%; 8 of 8 in Group 
B, 100%; 8 of 8 in Group C, 100%; and 4 of 6 in placebo group, 66.7%) experienced AEs. 
The most frequent TEAE in Group A was upper respiratory tract infection (37.5%) compared 
with placebo group; the most frequent TEAEs in Group B and Group C included decreased 
lymphocyte count (Group B, 87.5%; Group C, 100.0%), WBC count (Group B, 87.5%; 
Group C, 62.5%), and neutrophil count (Group B, 50%; Group C, 12.5%). The TEAEs noted 
in Group B during the repeated-dose period also included increased alanine aminotransferase 
(25%), gamma-glutamyltransferase (37.5%), and aspartate aminotransferase (12.5%), upper 
respiratory tract infection (12.5%), influenza (12.5%), chest pain (12.5%), lethargy (25%), 
and neck pain (12.5%); TEAEs in Group C during the repeated-dose period also included 
increased alanine aminotransferase (25%), decreased HR (12.5%), and mouth ulcer (12.5%); 
the TEAEs in placebo group included increased transaminase (16.7%), prolonged activated 
partial thromboplastin time (1/6, 16.7%), decreased hemoglobin (16.7%), upper respiratory 
tract infection (16.7%), diarrhea (16.7%), dizziness (16.7%), and palpitations (16.7%). 
Study CBP-307CN002 
This study is ongoing and there are no safety data available.  


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Study CBP-307CN003 
This study is ongoing and there are no safety data available.  
1.2.1.2. 
Pharmacokinetics 
CBP-307 given orally as a single dose was readily absorbed; drug concentrations peaked at 
approximately 6 hours after administration, with an elimination apparent terminal elimination 
half-life (t1/2) of approximately 25 hours (range of 23 to 29 hours). The time to maximum 
observed concentration (Cmax) in the blood was delayed from 6 hours to approximately 
10 hours when CBP-307 was given with a high-fat diet. Food consumption also increased 
exposure (Table 1). 
For the single-dose administration, CBP-307 exposure (based on Cmax and area under the 
concentration-time curve [AUCs]) increased with increasing dose following a single-dose 
administration (Table 1).  
Table 1: Pharmacokinetics Parameters in the Single-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Single-Dose 
Regimen PK 
Parameters 
Mean CBP-307 Single Dose ± SEM (n) 
0.1 mg 
0.25 mg 
0.5 mg 
(fasted) 
0.5 mg (fed)a 
2.5 mg 
AUClast 
(ng*h/mL) 
13.4 ± 3.54 
(n = 6) 
45.1 ± 5.25 
(n = 6) 
160 ± 22.8 
(n = 6) 
290 ± 28.1 
(n = 6) 
550 ± 96.3 
(n = 3) 
AUCinf 
(ng*h/mL) 
ND 
63.7 ± 2.14 
(n = 3) 
214 ± 58.3 
(n = 3) 
355 ± 44.3 
(n = 5) 
710 ± 164 
(n = 2) 
Cmax 
(ng/mL) 
0.537 ± 0.0931 
(n = 6) 
1.53 ± 
0.0935 
(n = 6) 
4.84 ± 0.706 
(n = 6) 
8.58 ± 1.11 
(n = 6) 
19.0 ± 3.55 
(n = 3) 
tmax 
(hours) 
7.33 ± 1.33 
(n = 6) 
5.33 ± 0.99 
(n = 6) 
5.00 ± 0.86 
(n = 6) 
10.67 ± 2.72 
(n = 6) 
6.00 ± 2.00 
(n = 3) 
t1/2 
(hours) 
ND 
23.3 ± 1.70 
(n = 3) 
28.8 ± 1.28 
(n = 3) 
26.0 ± 1.17 
(n = 5) 
22.8 ± 3.96 
(n = 2) 
Abbreviations: AUCinf = area under the curve at infinity; AUClast = area under the curve at the last time point; 
Cmax = maximum concentration; h = hour(s); mg = milligram(s); ND = not determinable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SEM = standard error of the mean; T1/2 = elimination half-life; Tmax = time to maximum 
concentration.  
a Study Part 1b: Cohort 3 from Part 1a returned to receive a single oral dose of CBP-307 at 0.5 mg under fed conditions. 
Source: Final report for Study CBP-307AU001. 
For the repeated-dose administration of CBP-307, the Cmax and AUCs increased with the 
higher administered dose (Table 2). At the steady-state timepoint on Day 28, the median 
CBP-307 tmax was 4 to 6 hours. The average t1/2 was similar, ranging 44 to 49 hours, and there 
were no dose-dependent changes in t1/2 within the dose range. The t1/2 was slightly prolonged 
after repeated-dose administration when compared with that after a single-dose 
administration. Moderate accumulation of CBP-307 (approximately 3 times the levels 


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following a single dose) was noted in plasma after QD administration for 14 consecutive 
days. 
Table 2: Pharmacokinetics Parameters in the Multiple-Dose CBP-307 Regimen 
(Study CBP-307AU001) 
Multiple-Dose 
Regimen PK 
Parameters 
Multiple-Dose Cohort 1  
CBP-307 Dosing, mg (± SD) (n) 
Multiple-Dose Cohort 2  
CBP-307 Dosing, mg (± SD) (n) 
Day 1 
0.1  
Day 28 
0.25  
Day 1 
0.15  
Day 28 
0.15  
AUC0-24 
(ng*h/mL) 
24.5 ± 3.26 
(n = 5) 
125 ± 12.4 
(n = 4) 
26.3 ± 7.45 
(n = 5) 
79.7 ± 27.3 
(n = 6) 
AUClast 
(ng*h/mL) 
NA 
203 ± 21.9 
(n = 4) 
NA 
131 ± 44.7 
(n = 6) 
Cmax 
(ng/mL) 
1.45 ± 0.214 
(n = 5) 
6.30 ± 0.588 
(n = 4) 
1.32 ± 0.422 
(n = 6) 
4.23 ± 1.45 
(n = 6) 
tmax 
(hours) 
6.80 ± 1.50 
(n = 5) 
6.50 ± 1.50 
(n = 4) 
5.00 ± 0.68 
(n = 6) 
4.33 ± 0.33 
(n = 6) 
Abbreviations:  AUC0-24 = area under the curve from time 0 to 24 hours; AUClast = area under the curve at the last time 
point; Cmax = maximum concentration; mg = milligram(s); NA = not applicable; ng/mL = nanogram(s) per milliliter; 
PK = pharmacokinetic; SD = standard deviation; Tmax = time to maximum concentration. 
Source: Final report for Study CBP-307AU001. 
1.3. 
Overview of Moxifloxacin 
Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic that binds to and inhibits the 
hERG IKr α subunit and causes a mean increase of the QTc interval of 6 ms after a single 
400-mg oral dose. Moxifloxacin is commonly used as a positive control in thorough QT 
(TQT) studies to satisfy the requirements of International Council for/Conference on 
Harmonisation (ICH) E14. 
Refer to the regional manufacturer package insert of AVELOX (moxifloxacin hydrochloride) 
tablets for additional information.2 
1.4. 
Study Rationale 
Regulatory guidance (ICH E14) has emphasized the need to obtain clear robust data on the 
effect of new chemical entities on electrocardiogram (ECG) parameters with focus on cardiac 
repolarization as measured by the QTc duration. Though many Phase 1, 2, and 3 trials may be 
conducted they usually have an insufficient sample size, infrequent sampling of ECG data, or 
the use of inadequate controls to overcome the high rate of spontaneous change in QTc 
duration. This has resulted in regulatory guidance recommending a dedicated or thorough 
trial to define the ECG effects of new drugs. 
This study will be done in healthy subjects to eliminate variables known to have an effect on 
ECG parameters (concomitant drugs, diseases, etc.). A supratherapeutic dose of CBP-307 is 
required to mimic the exposure in healthy subjects that may occur in the target population 
under the worst of circumstances (eg, concomitant use of cytochrome P450 [CYP]3A4 


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inhibitor, concomitant liver disease, presence of heart disease, taking more than the clinical 
dose prescribed) and to allow for PK to QTc modeling to assess the effect of drug 
concentration on cardiac repolarization. 
1.5. 
Benefit-risk Assessment 
Healthy subjects in the current study will not receive any health benefit (beyond that of an 
assessment of their medical status) from participating in the study. The risks of participation 
are primarily those associated with adverse reactions to the study treatments, although there 
may also be some discomfort from the collection of blood samples and other study 
procedures. More information about the known and expected benefits, risks, and reasonably 
anticipated AEs associated with CBP-307 may be found in the IB.1  
2. OBJECTIVES AND ENDPOINTS 
2.1. 
Objectives 
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma 
concentrations on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple 
oral doses of CBP-307 in healthy subjects. 
• To assess the PK of CBP-307 following administration of therapeutic and 
supratherapeutic multiple oral doses in healthy subjects. 
• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of 
CBP-307 on HR, PR and QRS intervals, and T-wave morphology. 
2.2. 
Endpoints 
2.2.1. 
Electrocardiogram Endpoints 
2.2.1.1. 
Primary 
The primary endpoint is the change-from-baseline QTcF (ΔQTcF). 
2.2.1.2. 
Secondary  
The secondary endpoints are: 
• Change-from-baseline HR, PR, QRS (∆HR, ∆PR, and ∆QRS); 


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• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (∆∆HR, ∆∆QTcF, 
∆∆PR, and ∆∆QRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
2.2.2. 
Pharmacokinetic Endpoints 
Pharmacokinetic parameters of CBP-307 will be determined if data allows: 
• area under the concentration‑time curve from time zero extrapolated to infinity 
(AUCinf) 
• area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24) 
• maximum observed concentration (Cmax) 
• time of the maximum observed concentration (tmax) 
Other PK parameters may also be reported. 
2.2.3. 
Safety Endpoints 
The safety outcome measures for this study are as follows: 
• incidence and severity of AEs 
• incidence of laboratory abnormalities, based on hematology, clinical chemistry, and 
urinalysis test results 
• 12-lead ECG parameters 
• vital signs measurements. 
3. INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, single-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only SAEs will be 
reported. After placebo administration to all subjects on Day -1, all AEs, whether 


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volunteered, elicited, or noted upon physical examination, will be recorded throughout the 
study (ie, from Day -1 until the end of the study).  
In this study, approximately 64 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 
Days 1, 2 to 5, 6 to 14, and on Day 15 (placebo will be administered to all subjects on 
Day -1).  
The following treatments will be administered: 
• A starting dose of CBP-307 for titration (0.1 mg, Day 1) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 2 to 5) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 6 to 14) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg)  
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) 
of 10 to 15 msec.  
An overview of the study design is shown in Figure 1. 
Figure 1: Study Schematic 
 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 and 2) with 
32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 
16 subjects. Subjects will be randomized to receive a treatment sequence that includes 4 treatments (CBP-307 therapeutic 
dose, CBP-307 supratherapeutic dose, moxifloxacin, or placebo [matched to CBP-307 or moxifloxacin]); assigned study 
treatments will be administered on Day 1, Days 2 to 5, Days 6 to 14, and Day 15. Dosing details are provided in Table 3. 
Blood samples for pharmacokinetic analysis will be collected predose and at each postdose cardiodynamic 
electrocardiogram timepoint.  
An end-of-study visit will occur on Day 28±2 days. 
Day 16
(Clinic 
Discharge)
Final 
Visit
(Day 28±2 
days)
Days 2 
to 5
Day 1
Day -2
(Check-in)
Inpatient Treatment Period
Day -28 
to -3
(Screening)
Days 6 
to 14
Day 15
Treatment Dosing Days
Cardiodynamic Recordings
Pharmacokinetic Samplings
Day -1


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Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
and will remain at the study site until discharge on Day 16. Treatment administration will 
occur on Days 1, 2 to 5, 6 to 14, and 15 under fasting conditions (all subjects will receive 
placebo on Day -1). Continuous cardiodynamic ECG monitoring and recording will begin at 
least 25 hours prior to the administration of study treatments on Day 1 and continue through 
24 hours after the administration of study treatments on Days 1, 5, 14, and 15 and at 
corresponding timepoints on the day before dosing, ie, Day -1. Blood samples for PK 
analysis will be collected predose and at each postdose cardiodynamic ECG timepoint. 
Subjects will return to the study site for a follow-up visit on Day 28±2 days. 
Baseline for the primary analysis will be determined from predose timepoints collected for 
25 hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 5, 14, and 
15. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 5, 
14, and 15; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, 
±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes 
for 12 to 24 hours postdose). Subjects will be inactive and in a supine position for at least 
10 minutes prior to and 5 minutes after each cardiodynamic ECG extraction timepoint, which 
will end immediately prior to the PK sampling. When timepoints for ECG extraction, safety 
ECGs, vital sign measurements, and blood draws coincide, procedures will be performed in 
said order. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 5 (therapeutic concentrations versus placebo), and Day 14 
(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 14, and 15. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 58 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 


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A Schedule of Assessments is presented in Appendix 6. 
3.2. 
Discussion of Study Design 
The purpose of this study is to evaluate the potential for CBP-307 to cause QT prolongation. 
As CBP-307 exposure affects heart rate, the primary endpoint for this study will be the QTcF. 
The study will be randomized and double-blind because randomization eliminates 
confounding by baseline variables and blinding eliminates confounding by co-interventions, 
thus eliminating the possibility that the observed effects of the intervention are because of 
differential use of other treatments.  
The sample size for this study is based on a formal statistical power calculation. 
Conducting the study in healthy subjects mitigates the potential confounding effects of the 
disease state and concomitant medications. Both male and female subjects will be included to 
eliminate similar known ECG variability effects. 
Additionally, because food has been shown to alter the PK of CBP-307, subjects will be 
fasted at least 10 hours prior to dose administration and remain fasted for 4 hours postdose on 
the days when PK samples are collected. 
Pharmacokinetic assessments of CBP-307 concentrations in plasma will be evaluated during 
the study. The timepoints for the PK sample collections are based on previous studies and are 
considered adequate to allow for the characterization of the drug’s PK after oral dosing. 
Furthermore, the chosen PK sample collection for CBP-307 is anticipated to be sufficient to 
allow reasonable estimation of t1/2 during the terminal elimination phase.  
3.3. 
Selection of Doses in the Study 
According to ICH E14, the highest therapeutic dose and a supratherapeutic dose are 
recommended for the QT/QTc study. The CBP-307 doses of 0.2 and 0.5 mg were chosen for 
evaluation in this study based on observed PK results in completed Phase 1 studies. To 
carefully monitor safety following the administration of CBP-307 doses in Group 1, CBP-307 
doses will be up-titrated as follows: subjects will receive a starting dose of 0.1 mg CBP-307 
on Day 1 followed by an up-titrated dose of 0.2 mg on Days 2 to 5. Prior clinical experience 
with CBP-307 has not demonstrated clinically significant abnormalities in laboratory test 
results in the majority of subjects or a dose-response relationship for safety based on AEs. 
A single dose of 0.5 mg is the planned supratherapeutic dose, which balances the 
characteristics of the study design with the safety of healthy subjects. Testing of CBP-307 at 
substantial multiples of the anticipated maximum therapeutic exposure is not clinically 
warranted due to the known safety and tolerability profile of CBP-307.  
Further details are provided in the IB.1 


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4. SELECTION OF STUDY POPULATION 
4.1. 
Inclusion Criteria 
Subjects must satisfy all of the following criteria at the screening visit unless otherwise 
stated: 
1. Males or females, of any race, between 18 and 60 years of age, inclusive. 
2. Body mass index between 18.0 and 30.0 kg/m2, inclusive. 
3. In good health, determined by no clinically significant findings from medical history, 
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory 
evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert’s 
syndrome based on total and direct bilirubin] is not acceptable) at screening and 
confirmed at check-in as assessed by the investigator (or designee). 
4. Females will not be pregnant or lactating, and females of childbearing potential and 
males will agree to use contraception as detailed in Appendix 4. Negative pregnancy 
test for females of childbearing potential at screening (blood test) and check-in (urine 
test); 
5. Supine diastolic blood pressure between 60 and 90 mmHg and systolic blood pressure 
between 90 and 140 mmHg (inclusive) at screening on a single measurement 
(confirmed by a single repeat, if necessary) following at least 5 minutes of rest; 
6. No clinically significant history or presence of ECG findings as judged by the 
investigator at screening and check-in, including each criterion as listed below: 
a. Normal sinus rhythm (HR between 60 bpm and 100 bpm inclusive); 
b. QTcF interval ≤450 msec for males and ≤470 msec for females; 
c. QRS interval ≤110 msec; and confirmed by manual over-read if >110 msec. 
d. PR interval ≤200 msec. 
7. Has serum potassium, calcium, and magnesium levels within the normal reference 
range at screening, as judged by the investigator. 
8. Able to swallow multiple tablets (based on subject’s verbal confirmation). 
9. Able to comprehend and willing to sign an ICF and to abide by the study restrictions. 
4.2. 
Exclusion Criteria 
Subjects will be excluded from the study if they satisfy any of the following criteria at the 
screening visit unless otherwise stated: 
1. Subject is mentally or legally incapacitated or has had significant history of recent 
mental health issues requiring medication and/or hospitalization at the time of the 
screening visit or expected during the conduct of the study. 
2. Significant history or clinical manifestation of any metabolic, allergic, dermatological, 
hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, 
neurological, respiratory, endocrine, or psychiatric disorder, as determined by the 


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investigator (or designee). Note: Childhood asthma that is considered recovered or 
seasonal allergies that are not currently active or requiring treatment are allowed. 
3. History of significant hypersensitivity, intolerance, or allergy to any drug compound, 
food, or other substance, unless approved by the investigator (or designee). 
4. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs, 
related compounds, or inactive ingredients. 
5. History of significant multiple and/or severe allergies (eg, latex allergy, band-aids, 
adhesive dressing, or medical tape), or has had an anaphylactic reaction or significant 
intolerability to prescription or nonprescription drugs. 
6. History of stomach or intestinal surgery or resection that would potentially alter 
absorption and/or excretion of orally administered drugs within 6 months prior to the 
first dose of study drug (uncomplicated appendectomy and hernia repair will be 
allowed). 
7. History or presence of: 
a. Hypokalemia, in the opinion of the investigator (or designee); 
b. Risk factors for Torsades de Pointes (eg, heart failure, cardiomyopathy, or 
family history of Long QT Syndrome); 
c. Sick sinus syndrome, second, or third degree atrioventricular block, 
myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged 
QT interval, or conduction abnormalities; 
d. Repeated or frequent syncope or vasovagal episodes; 
e. Hypertension, angina, bradycardia, or severe peripheral arterial circulatory 
disorders. 
8. Clinically significant abnormalities (as judged by the investigator in laboratory tests 
results [out-of-range results confirmed on repeat]), including but not limited to the 
following parameters: 
a. alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, or 
total bilirubin greater than 1.5 × upper limit of normal; 
b. hemoglobin <10 g/dL, WBC <3.0 ×109/L, neutrophils <1.5 ×109/L, 
lymphocytes <0.8 ×109/L and platelets <100 ×109/L or >1200 × 109/L; 
9. History or evidence of alcoholism or drug/chemical abuse within 2 years prior to 
check-in. 
10. Alcohol consumption of >10 units per week for males and females. One unit of 
alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill 
(25 mL) of spirits. 
11. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) 
at screening or check-in.  
12. Positive hepatitis panel, positive syphilis test, and/or positive human 
immunodeficiency virus test (Appendix 2).  


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13. Participation in a clinical study involving administration of an investigational drug 
(new chemical entity) in the past 28 days prior to the first dose of study treatment on 
Day 1. The 28-day window will be derived from the date of the last blood collection 
or dosing, whichever is later, in the previous study to Day 1 of the current study. 
14. Participation in a previous clinical study where subjects received CBP-307. 
15. Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 
28 days prior to first dose of study treatment on Day 1. 
16. Use or intend to use any prescription medications/products within 14 days prior to 
first dose of study drug (Day 1) and throughout the study, unless deemed acceptable 
by the investigator (or designee). Note: For females only, the use hormonal 
contraception, hormone replacement therapy or oral, implantable, transdermal, 
injectable, or intrauterine hormonal contraceptives within 14 days prior to Day 1 is 
not acceptable, except for Mirena®. 
17. Use or intend to use any drugs known to be significant inhibitors or inducers of CYP 
enzymes and/or P-gp, including St. John’s Wort, for days prior to the first dose of 
study drug and throughout the study. Appropriate sources will be consulted by the 
investigator or designee to confirm the lack of PK/PD interaction with the study drug. 
18. Use or intend to use slow-release medications/products considered to still be active 
within 14 days prior to check-in, unless deemed acceptable by the investigator (or 
designee). 
19. Use or intend to use any nonprescription medications/products including antacids, 
vitamins (especially those containing magnesium, aluminum, iron, or zinc), minerals, 
and phytotherapeutic/herbal/plant-derived preparations within 14 days prior to 
check-in, unless deemed acceptable by the investigator (or designee). 
20. Use of tobacco- or nicotine-containing products within 3 months prior to check-in, or 
positive cotinine at screening or check-in.  
21. Has been on a diet incompatible with the on-study diet (including an extreme diet 
which resulted in a significant weight change for whatever reason), in the opinion of 
the investigator, within the 28 days prior to the first dose of study treatment, and 
throughout the study. 
22. Consumption of caffeine/xanthine-containing foods or beverages within 48 hours 
prior to check-in until discharge. 
23. Ingestion of poppy seed-, Seville orange-, or grapefruit-containing foods or beverages 
within 7 days prior to check-in. 
24. Receipt of blood products within 2 months prior to check-in. 
25. Donation of blood from 3 months prior to screening, plasma from 2 weeks prior to 
screening, or platelets from 6 weeks prior to screening. 
26. Poor peripheral venous access. 
27. Subjects who, in the opinion of the investigator (or designee), should not participate 
in this study. 


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4.3. 
Subject Number and Identification 
Subjects will have a unique identification number used at screening. Eligible subjects will be 
assigned a subject number prior to the first dosing occasion. Assignment of subject numbers 
will be in ascending order and no numbers will be omitted (eg, Subjects 0101, 0102, 0103). 
The screening number will be used on all safety samples throughout the study. Replacement 
subjects (Section 4.4) will be assigned a subject number corresponding to the number of the 
subject he/she is replacing plus 1000 (eg, Subject 1101 replaces Subject 0101). 
Subjects will be identified by screening identification number or subject number only on all 
study documentation. A list identifying the subjects by subject number will be kept in the site 
master file. 
4.4. 
Subject Withdrawal and Replacement 
A subject is free to withdraw their informed consent from the study at any time or they may 
be withdrawn at any time at the discretion of the investigator or the sponsor for safety, 
behavioral, or the inability of the subject to comply with the protocol-required visits or 
procedures. In addition, a subject will be withdrawn from dosing if any of the following 
criteria are met: 
• change in compliance with any inclusion/exclusion criterion that is clinically relevant 
and affects subject safety as determined by the investigator (or designee) 
• noncompliance with the study restrictions that might affect subject safety or study 
assessments/objectives, as considered applicable by the investigator (or designee) 
• any clinically relevant sign or symptom that, in the opinion of the investigator (or 
designee), warrants subject withdrawal. 
If a subject is withdrawn from dosing, the sponsor will be notified and the date and reason(s) 
for the withdrawal will be documented in the subject’s electronic case report form (eCRF). If 
a subject is withdrawn from the study, efforts will be made to perform all follow-up 
assessments, if possible (Appendix 6). Other procedures may be performed at the 
investigator’s (or designee’s) and/or sponsor’s discretion. If the subject is in-house, these 
procedures should be performed before the subject is discharged from the clinic. The 
investigator (or designee) may also request that the subject return for an additional follow-up 
visit. All withdrawn subjects will be followed until resolution of all their AEs or until the 
unresolved AEs are judged by the investigator (or designee) to have stabilized. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, effort should be made to document subject outcome, if possible. 
The investigator should inquire about the reason for withdrawal, request the subject to return 
for a final visit, if applicable, and follow-up with the subject regarding any unresolved AEs.  
Subjects who are withdrawn for reasons not related to study treatment may be replaced 
following discussion between the investigator and the sponsor. Subjects withdrawn as a result 
of AEs thought to be related to the study treatment will generally not be replaced. 


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4.5. 
Study Termination 
The study may be discontinued at the discretion of the investigator (or designee), sponsor, or 
sponsor’s medical monitor if any of the following criteria are met: 
• investigator decides to terminate the study due to safety concerns such as AEs 
unknown to date (ie, not previously reported in any similar investigational study drug 
trial with respect to their nature, severity, and/or duration) 
• increased frequency, severity, and/or duration of known, anticipated, or previously 
reported AEs (this may also apply to AEs defined at check-in as baseline signs and 
symptoms) 
• medical or ethical reasons affecting the continued performance of the study 
• difficulties in the recruitment of subjects 
• cancelation of drug development 
• sponsor requests for termination (eg, due to financial or management reasons, etc.) 
under the premise to fully protect the safety and rights of subjects  
• health authority or ethics committee (EC) orders the termination of the trial for any 
reason. 
Definition of end-of-treatment and end-of-study  
• end-of-treatment is completion of safety follow-up or withdrawal from the study. 
End-of-study is the last visit by the last subject. 
5. STUDY TREATMENTS 
Study treatments are defined as any investigational product (IP), non-investigational product 
(non-IP), placebo, or medical device intended to be administered to a study subject according 
to the study protocol. 
Note that in several countries, IP and non-IP are referred to as IMP and non-IMP, 
respectively. 
5.1. 
Investigational Products 
The details regarding the storage, preparation, destruction, and administration of each 
treatment shown in Table 3 will be provided in a separate document. Approximately 
64 healthy subjects (at least 30% for each sex) will be randomized into 2 groups (Group 1 
and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A and 2B) and 
each sub-group will be randomized with 16 subjects.  
 


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Table 3: Study Treatments 
Study Treatment 
Name 
Treatmen
t Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
Dosage 
Formulation 
 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(
s) 
 
0.1 mg 
Not 
applicable 
400 mg 
Not 
applicable 
Dosage Frequency   
 
 
 
 
Day -1 Group 1 
 
1 capsule 
 
 
 Group 2A 
 
1 capsule 
 
 
 Group 2B 
 
1 capsule 
 
 
Day 1 Group 1 
1 × 0.1 mg 
 
 
1 tablet 
Group 2A 
 
1 capsule 
1 × 400 mg 
 
Group 2B 
 
1 capsule 
 
1 tablet 
Days 2 to 5 Group 1 
2 × 0.1 mg 
 
 
 
Group 2A 
 
2 capsules 
 
 
Group 2B 
 
2 capsules 
 
 
Days 6 to 14 Group 1 
5 × 0.1 mg 
 
 
 
Group 2A 
 
5 capsules 
 
 
Group 2B 
 
5 capsules 
 
 
Day 15 Group 1 
 
 
 
1 tablet 
Group 2A 
 
 
 
1 tablet 
Group 2B 
 
 
1 × 400 mg 
 
Route of 
Administration 
 
Oral 
Oral 
Oral 
Oral 
Accountability 
 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
electronic 
case report 
form (eCRF). 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
eCRF. 
The quantity 
administered, 
date 
administered, 
and lot 
number of 
investigationa
l product is to 
be recorded 
on each 
subject's 
eCRF. 
Dosing 
Instructions 
 
Treatments 
will be 
administered 
after the 
Treatments 
will be 
administered 
after the 
Treatments 
will be 
administered 
after the 
Treatments 
will be 
administered 
after the 


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Study Treatment 
Name 
Treatmen
t Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox2) 
Moxifloxacin 
Matched 
Placebo 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximatel
y 240 mL of 
room 
temperature 
water. 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximatel
y 240 mL of 
room 
temperature 
water. 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximatel
y 240 mL of 
room 
temperature 
water. 
completion of 
all predose 
procedures 
and after a 
fast of at least 
10 hours with 
approximatel
y 240 mL of 
room 
temperature 
water. 
 
All supplies of the IMP, both bulk and subject-specific, will be stored in accordance with the 
manufacturer’s or pharmacy’s instructions. Until dispensed to the subjects, the study 
treatments will be stored at the study site in a location that is locked with restricted access. 
5.2. 
Study Treatment Administration 
Each dose of study treatment (CBP-307, placebo, or moxifloxacin) will be administered 
orally following an overnight fast of at least 10 hours, with approximately 240 mL of room 
temperature water. Additionally, because food has been shown to alter the PK of CBP-307, 
subjects will be fasted at least 10 hours prior to dose administration and remain fasted for 
4 hours postdose on the days when PK samples are collected. 
Subjects will be dosed in numerical order while sitting or standing but not be permitted to lie 
supine for 2 hours after treatment administration, except as necessitated by the occurrence of 
an AE(s) and/or study procedures. 
5.3. 
Randomization 
This is a double-blind randomized study. Subjects will be randomized to one of the treatment 
sequences before administration of the first dose of study treatment. A randomization list will 
be generated by a statistician using a computer-generated pseudo-random permutation 
procedure. The randomization date is to be documented in the subject’s medical record and 
on the enrollment eCRF. A computer-generated randomization schedule and emergency 
code-break envelopes will be provided to the study site. Randomization details will be 
included in the randomization specification. 
5.4. 
Blinding 
This is a double-blinded study. The following controls will be employed to maintain the 
double-blind status of the study: 
• The placebo will be identical in appearance to CBP-307 or moxifloxacin. 


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• The investigator and other members of staff involved with the study will remain 
blinded to the treatment randomization code during the assembly procedure. 
• Interim bioanalytical data will be provided to Covance Early Clinical Biometrics in a 
blinded manner. 
To maintain the blind, the investigator will be provided with a sealed randomization code for 
each subject, containing coded details of the treatment. These individually sealed envelopes 
will be kept in a limited access area that is accessible 24 hours a day. If, in order to manage 
subject safety or to support dose escalation decisions (in the event of possibly 
treatment-related SAEs or severe AEs), the decision to unblind resides solely with the 
investigator. Whenever possible, and providing it does not interfere with or delay any 
decision in the best interest of the subject, the investigator will discuss the intended 
code-break with the sponsor. If it becomes necessary to break the code during the study, the 
date, time, and reason will be recorded in the subject's source data and on the individual 
envelope and will be witnessed by a second person. 
5.5. 
Treatment Compliance 
The following measures will be employed to ensure treatment compliance: 
• All doses will be administered under the supervision of suitably qualified study site 
staff. 
• Immediately after dose administration, visual inspection of the mouth and hands will 
be performed for each subject. 
• At each dosing occasion, a predose and postdose inventory of IMP will be performed.   
5.6. 
Drug Accountability 
The investigator (or designee) will maintain an accurate record of the receipt of study 
treatments (CBP-307, moxifloxacin, placebo-matched CBP-307, and placebo-matched 
moxifloxacin) received. In addition, an accurate drug disposition record will be kept, 
specifying the amount dispensed to each subject and the date of dispensing. This drug 
accountability record will be available for inspection at any time. At the completion of the 
study, the original drug accountability record will be available for review by the sponsor 
upon request. 
For each batch of unit doses, the empty used unit dose containers will be discarded upon 
satisfactory completion of the compliance and accountability procedures. Any unused 
assembled unit doses will be retained until the completion of the study. 
At the completion of the study, all unused study treatments (CBP-307, moxifloxacin, 
placebo-matched CBP-307, and placebo-matched moxifloxacin) will be disposed of by the 
study site’s pharmacy (RAH Pharmacy), per the sponsor’s written instructions. If destruction 
is authorized to take place at the study site’s pharmacy, the investigator must ensure that the 
materials are destroyed in compliance with applicable environmental regulations and 
institutional policy. All study drug destructions must be adequately documented. 


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6. CONCOMITANT THERAPIES AND OTHER RESTRICTIONS 
6.1. 
Concomitant Therapies 
Subjects will refrain from the use of any prescription or nonprescription medications/products 
during the study until the follow-up visit, unless the investigator (or designee) and/or sponsor 
have given their prior consent. Medications taken within 28 days before study treatment 
administration will be documented as a prior treatment. Treatments taken after study 
treatment administration will be documented as concomitant treatments. 
Paracetamol/acetaminophen (2 g/day for up to 3 consecutive days) is an acceptable 
concomitant medication. The administration of any other concomitant medications during the 
study is prohibited without prior approval of the investigator (or designee), unless its use is 
deemed necessary for the treatment of an AE. Any medication taken by a subject during the 
course of the study and the reason for its use will be documented in the source data.  
Females will refrain from the use of hormone replacement therapy and oral, implantable, 
transdermal, injectable, or intrauterine hormonal contraceptives (with the exception of 
Mirena®) during the study until the follow-up visit (See Appendix 4). 
6.2. 
Diet 
While confined at the study site, subjects will receive a standardized diet at scheduled times 
that do not conflict with other study-related activities. Subjects will be fasted overnight (at 
least 10 hours) before the collection of blood samples for clinical laboratory evaluations. 
On the days with PK assessments (Appendix 6), the subjects will be fasted overnight (at least 
10 hours) prior to dosing and refrain from consuming water from 1 hour predose until 1 hour 
postdose, excluding the amount of water consumed at dosing. Food is allowed from 4 hours 
postdose. At all other times during the study, subjects may consume water ad libitum. 
Foods and beverages containing poppy seeds, grapefruit, or Seville oranges will not be 
allowed from 7 days prior to check-in until follow-up visit on Day 28±2 days. 
Consumption of caffeine/xanthine-containing foods and beverages will not be allowed from 
48 hours before check-in until discharge on Day 16. 
Consumption of alcohol will not be permitted from 72 hours prior to check-in until discharge 
on Day 16 and alcohol intake will be limited to a maximum of 2 units/day on all other days, 
whilst not at the study site, from screening to 72 hours prior to the follow-up visit on 
Day 28±2 days.  
6.3. 
Smoking 
Subjects will not be permitted to use tobacco- or nicotine-containing products within 
3 months prior to check-in until the follow-up visit. 


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6.4. 
Exercise 
Subjects are required to refrain from strenuous exercise from 7 days before check-in until the 
follow-up visit (Day 28±2 days) and will otherwise maintain their normal level of physical 
activity during this time (ie, will not begin a new exercise program nor participate in any 
unusually strenuous physical exertion). 
6.5. 
Blood Donation 
Subjects are required to refrain from donation of blood from 3 months prior to screening, 
plasma from 2 weeks prior to screening, and platelets from 6 weeks prior to screening until 
3 months after the follow-up visit. 
7. STUDY ASSESSMENTS AND PROCEDURES 
Every effort will be made to schedule and perform the procedures as closely as possible to the 
nominal time, giving considerations to appropriate posture conditions, practical restrictions, 
and the other procedures to be performed at the same timepoint. 
The highest priority procedures will be performed closest to the nominal time. The order of 
priority for scheduling procedures around a timepoint is (in descending order of priority): 
• dosing 
• continuous ECG extraction window 
• pharmacokinetic blood samples 
• safety assessments  
• any other procedures. 
This study includes a screening period (Day -28 to Day -2), a treatment period (Days -1 to 
16), and a follow-up period (Day 28 ±2 days).  
The defined abnormal vital sign measurements (Exclusion Criteria #4) at check-in (Day -2) 
or baseline (Day -1 predose) will only be considered exclusionary if judged applicable by the 
investigator. For confirmation of enrollment eligibility based on pulse rate, the pulse rate 
assessed by vital signs, rather than the 12-lead ECG, will be used. For all subjects, the 
screening, check-in, or baseline blood pressure, pulse rate, and respiratory rate may be 
repeated after 5 to 10 minutes if the initial reading is believed to be atypical for the subject. 
7.1. 
General Assessments 
7.1.1. 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in order 
to study their possible association with subject safety and treatment effectiveness. 


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7.1.2. 
Medical History 
At the timepoint specified in Appendix 6, the investigator or designee will collect a complete 
medical and surgical history. Medical history will include information on the subject’s 
concurrent medical conditions and any events occurring prior to the first dose of study 
treatment. All findings will be recorded on the medical history eCRF. 
7.2. 
Electrocardiography Assessments 
7.2.1. 
Continuous 12-lead Electrocardiogram Recording 
Continuous 12-lead digital ECG recording will be performed as specified in Appendix 6. All 
ECG data will be collected using a Holter (or Mortara Surveyor) ECG continuous 12-lead 
digital recorder. The 12-lead Holter (or Mortara Surveyor) ECG equipment will be supplied 
and supported by ERT (eResearch Technology Inc., Philadelphia, PA). The continuous 
12-lead digital ECG data will be stored onto SD memory cards.  
The ECGs to be used in the analyses will be selected by predetermined timepoints as defined 
in Appendix 6 and will be read centrally by ERT (eResearch Technology Inc., Philadelphia, 
PA). The following principles will be followed in ERT’s core laboratory: 
• ECG analysts are blinded to the subject, visit, and treatment allocation. 
• Baseline and on-treatment ECGs for a particular subject will be over-read on the same 
lead and will be analyzed by the same reader. 
The primary analysis lead is lead II. If lead II is not analyzable, then the primary lead of 
analysis will be changed to another lead for the entire subject data set. 
The 12-lead ECGs will be extracted in up to 10 replicates at the predefined timepoints and 
subjects will be inactive and in a supine position for at least 10 minutes prior to and 5 minutes 
after each nominal time. 
7.2.1.1. 
TQT Plus Extraction Technique 
Ten 14-second digital 12-lead ECG tracings will be extracted from the continuous Holter (or 
Mortara Surveyor) recordings using the ‘TQT Plus method’, a computer-assisted and 
statistical process utilized by ERT. The method enables extraction of ECGs with the lowest 
HR variability and noise within the protocol-specified extraction time window (eg, the HR 
and QT changes from beat-to-beat in the range of <10%). At each protocol-specified 
timepoint, 10 ECG replicates will be extracted from a 5-minute “ECG window” (typically, 
the last 5 minutes of the 15-minute period when the subject is maintained in a supine, quiet 
position). 
7.2.1.2. 
Expert Precision QT Analysis 
Expert precision QT analysis will be performed on all analyzable (non-artifact) beats in the 
10 ECG replicates. Statistical quality control procedures are used to review and assess all 
beats and identify “high” and “low” confidence beats using several criteria, including: 


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• QT or QTc values exceeding or below certain thresholds (biologically unlikely). 
• RR values exceeding or below certain thresholds (biologically unlikely). 
• Rapid changes in QT, QTc, or RR from beat-to-beat. 
Measurements of all primary ECG parameters (QT, QTc, RR) in all recorded beats of all 
replicates that are deemed “high confidence” will be performed using COMPAS software. 
All low-confidence beats will be reviewed manually and adjudicated using pass-fail criteria. 
The final QC assessment will be performed by a cardiologist. The beats found acceptable by 
manual review will be included in the analysis. The median QT, QTc, and RR values from 
each extracted replicate will be calculated, and then the mean of all available medians from a 
nominal timepoint will be used as the subject’s reportable value at that timepoint. 
Categorical T-wave morphology analysis and the measurement of PR and QRS interval of the 
ECG (QRS) intervals will be performed manually in 3 of the 10 ECG replicates at each 
timepoint. Each fiducial point (onset of P-wave, onset of Q-wave, offset of S-wave, and 
offset of T-wave) will be electronically marked. 
For T-wave morphology and U-wave presence, treatment-emergent changes will be assessed 
(ie, changes not present at baseline). For each category of T-wave morphology and U-waves, 
the category will be deemed as present if observed in any replicate at the timepoint. For 
baseline, the category will be deemed as present if observed in any replicate from all 
timepoints that constitute baseline. 
7.2.2. 
Safety 12-lead Electrocardiogram 
Resting 12-lead ECGs will be recorded after the subject has been supine and at rest for at 
least 5 minutes at the times indicated in the Schedule of Assessments in Appendix 6. Single 
12-lead ECGs will be repeated twice, and an average taken of the 3 readings, if either of the 
following criteria applies: 
• QT interval corrected for HR using Fridericia’s method (QTcF) is >500 ms 
• QTcF change from the baseline (predose) is >60 ms. 
Additional 12-lead ECGs may be performed at other times if judged to be clinically 
appropriate or if the ongoing review of the data suggests a more detailed assessment of ECGs 
is required. The investigator (or designee) will perform a clinical assessment of each 12-lead 
ECG. 
7.3. 
Pharmacokinetic Assessments  
7.3.1. 
Pharmacokinetic Blood Sample Collection and Processing 
Blood samples (approximately 1 × 3 mL for CBP-307 and moxifloxacin assays) will be 
collected by venipuncture or cannulation at the times indicated in the Schedule of 
Assessments in Appendix 6. Procedures for collection, processing, and shipping of PK blood 
samples will be detailed in a separate document.  


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7.3.2. 
Analytical Methodology 
Plasma concentrations of CBP-307 and moxifloxacin will be determined using a validated 
analytical procedure. Specifics of the analytical method will be provided in a separate 
document.  
7.4. 
Safety and Tolerability Assessments 
7.4.1. 
Adverse Events 
Adverse event definitions, assignment of severity and causality, and procedures for reporting 
SAEs are detailed in Appendix 1. 
The condition of each subject will be monitored from the time of signing the ICF until the 
follow-up visit. Subjects will be observed for any signs or symptoms and asked about their 
condition by open questioning, such as “How have you been feeling since you were last 
asked?”, at least once each day while resident at the study site and each study visit. Subjects 
will also be encouraged to spontaneously report AEs occurring at any other time during the 
study. 
All nonserious AEs, whether reported by the subject voluntarily or upon questioning, or 
noted on physical examination, will be recorded from initiation of placebo administration to 
all subjects (Day -1) until study completion. If AEs that occur in the screening prior to 
placebo administration to all subjects (Day -1) are considered to be related to the study 
procedure, they should be also collected. Serious AEs will be recorded from the time the 
subject signs the ICF until study completion. The nature, time of onset, duration, and severity 
will be documented, together with an investigator’s (or designee’s) opinion of the 
relationship to study treatment. 
Adverse events recorded during the course of the study will be followed up, where possible, 
to resolution or until the unresolved AEs are judged by the investigator (or designee) to have 
stabilized. This will be completed at the investigator’s (or designee’s) discretion. 
7.4.2. 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected for clinical laboratory evaluations at the times 
indicated in the Schedule of Assessments in Appendix 6. Clinical laboratory evaluations are 
listed in Appendix 2. 
A serum qualitative pregnancy or urine test (females only) and follicle-stimulating hormone 
test (postmenopausal females only) will be performed at the timepoints specified in 
Appendix 6. A positive urine pregnancy test will be confirmed with a serum pregnancy test. 
All pregnancies should be reported as specified in Appendix 1. 
Additional clinical laboratory evaluations will be performed at other times if judged to be 
clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of clinical laboratory safety evaluations is required. At the discretion of the 
investigator, clinically significant clinical laboratory assessments may be confirmed by repeat 
sampling. If the clinical significance is confirmed, subjects will be excluded from 


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participation or, if already included, will be followed until normalization of the test result or 
for as long as the investigator considers necessary. 
Subjects will be asked to provide urine samples for drugs of abuse screen and cotinine test, 
and will undergo an alcohol breath test at the times indicated in the Schedule of Assessments 
in Appendix 6. For all female subjects, a pregnancy test will be performed at the times 
indicated in the Schedule of Assessments in Appendix 6.   
An investigator (or designee) will perform a clinical assessment of all clinical laboratory data. 
7.4.3. 
Vital Signs 
Supine blood pressure, supine pulse rate, respiratory rate, and tympanic temperature will be 
assessed at the times indicated in the Schedule of Assessments in Appendix 6. Vital signs 
may also be performed at other times if judged to be clinically appropriate or if the ongoing 
review of the data suggests a more detailed assessment of vital signs is required. 
All measurements will be performed singly. For all subjects, the screening, check-in, or 
baseline blood pressure, pulse rate, and respiratory rate may be repeated after 5 to 10 minutes 
if the initial reading is believed to be atypical for the subject. 
Subjects must be supine for at least 5 minutes before blood pressure and pulse rate 
measurements. 
7.4.4. 
Physical Examination 
A full physical examination will be performed at the timepoints specified in the Schedule of 
Assessments in Appendix 6. Physical examinations include general appearance, head, eyes, 
ears, nose, and throat, neck (including thyroid and nodes), cardiovascular, respiratory, 
gastrointestinal, renal, neurological, musculoskeletal, skin, and others. 
Height, weight, and body mass index will be assessed at screening. 
8. SAMPLE SIZE AND DATA ANALYSIS 
8.1. 
Determination of Sample Size 
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 
2 groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups 
(Group 2A and 2B) and each sub-group will be randomized with 16 subjects. 
Sample Size for Primary Analysis: 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-msec QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-307 
in the study. This power is estimated approximately using a 2-sample t-test. The calculation 
assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 3 msec and a 


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standard deviation (SD) of the ΔQTcF of 8 msec for both CBP-307 and placebo treatment 
groups. Note that this calculation is conservative, since it does not take into account any gain 
in precision due to the use of all data of each subject with the help of a linear mixed-effects 
model. The concentration-QTc analysis method is supported by Darpo et al 20153 and 
Ferber et al, 2015,4 and consistent with the experiences from 25 recent TQT studies. 
Sample Size Considerations for Assay Sensitivity: 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that the 
ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 msec (ie, the lower bound of the 
2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 msec). In a similarly 
designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the standard 
error (SE) for the prediction of the QT effect of moxifloxacin based on the exposure-response 
analysis was 1.24 msec. The within-subject SD of ΔQTcF in the referred study was 5.4 msec 
based on the by-timepoint analysis. If the effect of moxifloxacin is assumed to be 10 msec, 
the SE of 1.24 msec corresponds to an effect size of (10-5)/(1.24×sqrt[24])=0.82, where the 
effect size is the effect assumed under the alternative hypothesis divided by the SD of the test 
variable. This value should be compared to the effect size of 0.64 required to guarantee a 
power of at least 95% in a paired t-test situation with a sample size of 28 evaluable subjects. 
In other words, based on this calculation, a power of at least 95% will be obtained as long as 
the variability of the ΔQTcF, as measured by its within-subject SD from the by-timepoint 
analysis, does not exceed 6.9 msec (ie, 128% [= 0.82/0.64] of the 5.4 msec observed in the 
referred study assuming the ratio of effective sizes is consistent with inverse ratio of 
within-subject SD). The number also agrees with recent recommendations of the FDA, which 
propose at least 20 subjects.5 
8.2. 
Analysis Populations 
8.2.1. 
Cardiodynamic Population 
The QT/QTc population will include all subjects in the safety population with measurements 
at baseline as well as on-treatment with at least 1 postdose timepoint with a valid ΔQTcF 
value. The QT/QTc population will be used for the by-timepoint and categorical analyses of 
the cardiodynamic ECG parameters. 
The PK/QTc population will include all subjects who are in both the QT/QTc and PK 
populations with at least 1 pair of postdose PK and ∆QTcF data from the same timepoint as 
well as subjects in the QT/QTc population who received placebo. The PK/QTc population 
will be used for the concentration-QTc analysis and assay sensitivity. PK/QTc population 
will be defined for CBP-307, and for moxifloxacin.  
The as-treated principle will be applied to all analysis populations mentioned below. 
8.2.2. 
Pharmacokinetic Population 
The PK population will include all subjects who received at least 1 dose of investigational 
product and have evaluable PK data of any of the analytes (CBP-307 and moxifloxacin). A 
subject will be excluded from the PK summary statistics and statistical analysis if the subject 
has an AE of vomiting that occurs at or before 2 times median time to maximum 
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8.2.3. 
Safety Population 
The safety population will include all subjects who received at least 1 dose of investigational 
product drug (therapeutic and supratherapeutic doses of CBP-307, moxifloxacin, or placebo). 
8.3. 
Cardiodynamic ECG Analyses 
Baseline for Cardiodynamic ECG Assessments 
Baseline for the assessment of the ECG effect of CBP-307 (CBP 307 in Group 1 versus 
placebo in Groups 2A and 2B) will be time-matched values on Day -1.  
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
• Group 2A: For moxifloxacin administered on Day 1, baseline will be Day 15, on 
which subjects are administered placebo. For placebo-correction in this group, 
placebo values will be derived from Day 14 on which subjects are administered 
placebo, and baseline will be obtained on Day -1. 
• Group 2B: For moxifloxacin administered on Day 15, baseline will be Day 1, on 
which subjects are administered placebo. For the placebo-correction in this group, 
Day -1 values will be used as placebo (no treatment) and baseline will be obtained on 
Day 14. 
Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as 
the dependent variable, time-matched concentrations of CBP-307 as the exploratory variate 
(0 for placebo), treatment (active=1 or placebo=0), and time (ie, postbaseline timepoints on 
Days 1, 5, and 14 categorical) as fixed effects, and a random intercept and slope per subject.6  
The degrees of freedom estimates will be determined by the Kenward-Roger method. From 
the model, the slope (ie, the regression parameter for the CBP-307 concentration) and the 
treatment effect-specific intercept will be estimated together with 2-sided 90% CI. The 
estimates for the time effect will be reported with degrees of freedom and SE.  
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-time point analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single predose timepoint and all postdose timepoints on Days 1, 5, 
and 14, and Days 1 and 15 for active versus placebo and moxifloxacin versus placebo, 
respectively. All times are relative to the time of dosing on that day which is considered the 
first dose for the assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the 
first dose of study treatment is on Day 1. 
The geometric mean of the individual Cmax values for CBP-307 concentrations for subjects in 
the active drug groups on each of Days 5 and 14 will be determined, respectively. The 
predicted effect and its 2-sided 90% CI for placebo-corrected change-from-baseline QTcF 


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(ΔΔQTcF) (ie, slope estimate × concentration + treatment effect-specific intercept) at this 
geometric mean Cmax will be obtained.  
To evaluate the adequacy of model fit with respect to the assumption of linearity, the 
observed ΔQTcF values adjusted by population time effect estimated from the model will be 
used. These individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values equal the observed 
individual ΔQTcFi,k for subject i administered with active drug or placebo at timepoint k 
minus the estimated population mean placebo effect at timepoint k (ie, time effect). A decile 
plot, ie, plot of the deciles of observed concentrations and the mean placebo-adjusted ΔQTcF 
(ΔΔQTcF) and 90% CI at the median concentration within each decile will be given. The 
regression line presenting the model-predicted ΔΔQTcF7 will be added to evaluate the fit of a 
linear model and visualize the concentration-response relationship. The placebo-adjusted 
ΔQTcFi,j equals the individual ΔQTcFi,j for subject i administered with CBP-307 at timepoint 
j minus the estimation of time at timepoint j (ie, time effect). Additional exploratory analyses 
(via graphical displays and/or model fitting) will include accounting for a delayed effect 
(hysteresis) and the justification for the choice of PD model (linear versus nonlinear) as 
follows. 
Criteria for Negative QT Assessment 
If the upper bound of the 2-sided 90% CI of the predicted QTc effect of ΔΔQTcF at the 
observed geometric mean Cmax on Days 5 and 14 as well as clinically relevant plasma levels 
is below 10 msec (ie, the upper bound of the 2-sided 90% CI at the geometric mean Cmax 
<10 msec), it can be concluded that CBP-307 does not cause clinically concerning QT 
prolongation within the observed plasma concentration ranges.  
Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF for each postbaseline timepoint and the mean concentration of CBP-307 at the same 
timepoints. In addition, hysteresis plots will be given for LS mean ΔΔQTcF and the mean 
concentrations. If a QT effect (ΔΔQTcF) >10 msec cannot be excluded from the by-timepoint 
analysis in the active dose groups on Days 5 and 14; and the mean peak ΔΔQTcF effect is 
observed at the same timepoint in the by-timepoint analysis in the active dose groups on 
Days 5 and 14; and if the difference (delay) between the time to reach the peak QTc effect 
(ΔΔQTcF) and peak plasma concentration (tmax) in the plot (ΔΔQTcF versus CBP-307) of 
more than 1 hour is observed in a consistent way for the active dose groups on Days 5 and 14, 
other concentration-QTc models, such as a model with an effect compartment, may be 
explored. With the provision stated above, hysteresis will be assumed if this curve shows a 
counterclockwise loop. A significant treatment effect-specific intercept may also be 
indicative of hysteresis or model misspecification, if it cannot be explained by a nonlinear 
relationship. 
Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile plots for the 
standardized residuals and the random effects, scatter plots of standardized residuals versus 
concentration and versus fitted values, and box plots of standardized residuals versus nominal 


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time and versus active treatment will be produced. The scatter plot of standardized residuals 
versus concentration by locally estimated scatterplot smoothing (LOESS) fitting (ie, locally 
weighted scatterplot smoothing8 lines) also will be produced with an optimal smoothing 
parameter selected by the Akaike information criterion with a correction.9 In addition, a 
scatter plot of observed concentration and ΔQTcF with a LOESS smooth line with 90% CI 
and a linear regression line will also be provided to check the assumption of a linear 
concentration-QTc relationship. If there is an indication that a linear model is inappropriate, 
additional models may be fitted, such as an E-max model. The concentration-QTc analysis 
will then be repeated for the model found to best accommodate the nonlinearity detected. 
Assay Sensitivity 
Assay sensitivity will be demonstrated by similar concentration-QTc analysis of 
moxifloxacin data. If the slope of the concentration-QTc (change-from-baseline QTcF) for 
moxifloxacin is statistically significant at 10% level for 2-sided test and the lower bound of 
the 2-sided 90% CI of the predicted effect is above 5 msec at the observed geometric mean 
Cmax of the 400-mg dose, assay sensitivity will be deemed to have been demonstrated. 
By-Timepoint Analysis 
The analysis for QTcF for CBP-307 versus placebo will be based on a linear mixed-effects 
model with change-from-baseline QTcF (ΔQTcF) as the dependent variable, time (ie, 
postbaseline timepoints on Days 1, 5, and 14: categorical), treatment (therapeutic dose of 
CBP-307 and supratherapeutic dose of CBP-307 on Day 14, and corresponding placebo), and 
time-by-treatment interaction as fixed effects. An unstructured covariance matrix will be 
specified for the repeated measures at postdose timepoints within subjects. If the model with 
unstructured covariance matrix fails to converge, other covariance matrices such as 
compound symmetry and autoregressive will be considered. From this analysis, the LS mean, 
SE, and 2-sided 90% CIs will be calculated for the contrast “CBP-307 versus placebo” for 
each day of Days 1, 5, and 14 at each postbaseline timepoint on Days 1, 5, and Day 14, 
respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo 
at postbaseline timepoints on Day 1 and Day 15. A linear mixed-effects model will be used 
with ΔQTcF as the dependent variable and time (ie, postbaseline timepoints on Days 1 and 
15: categorical), treatment (moxifloxacin and placebo), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. An unstructured 
covariance matrix will be specified for the repeated measures at postbaseline timepoints for 
subject within visit. The model will also include a subject-specific random effect. If the 
model with an unstructured covariance matrix fails to converge, other covariance matrices, 
such as compound symmetry or autoregressive, will be considered. From this analysis, the LS 
mean, SE, and 2-sided 90% CIs will be calculated for the contrast “moxifloxacin versus 
placebo” at each postbaseline timepoint, respectively. 
For HR, PR, and QRS intervals, the analysis will be based on the change-from-baseline 
postdose (ΔHR, ΔPR, ΔQRS). The same (by-timepoint analysis) model will be used as 
described for QTcF. The LS mean, SE, and 90% CI from the statistical modeling for both 


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change-from-baseline and placebo-corrected change-from-baseline values will be listed in the 
tables and graphically displayed. 
Categorical Analyses 
The analysis results for categorical outliers, T-wave morphology, and U-wave presence will 
be summarized in frequency tables with counts (percentages) for both the number of subjects 
and the number of timepoints. For categorical outliers, the number (percentage) of subjects as 
well as timepoints who had increases in absolute QTcF values >450 and ≤480 msec, >480 
and ≤500 msec, or >500 msec, and changes from predose baseline of >30 and ≤60 msec, or 
>60 msec; increase in PR from predose baseline >25% to a PR > 200 msec; increase in QRS 
from predose baseline >25% to a QRS >120 msec; decrease in HR from predose baseline 
>25% to an HR <50 bpm; and increase in HR from predose baseline >25% to an HR 
>100 bpm will be determined. For T-wave morphology and U-wave presence, the analyses 
will be focused on change from baseline (ie, treatment-emergent changes). 
8.4. 
Pharmacokinetic Analyses 
The analyses will be carried out on the PK analysis population. All PK parameters will be 
presented by listings and descriptive summary statistics (mean, SD, median, minimum, 
maximum geometric mean, and geometric coefficient of variation) separately by group. 
Individual and mean plasma CBP-307 and moxifloxacin concentration versus time data will 
be tabulated and plotted by dose level. Graphical displays of PK data may be provided as 
well.  
For each subject, the following PK parameters will be calculated, whenever possible, based 
on the plasma concentration for CBP-307 and moxifloxacin, according to the model 
independent approach: 
• Cmax 
• tmax 
• AUC0-24  
• AUCinf 
• apparent terminal elimination rate constant (λZ) 
• t1/2  
• apparent total clearance (CL/F) 
• apparent volume of distribution during the terminal phase (Vz/F)  
Pharmacokinetic calculations will be performed, if appropriate, using commercial software 
such as Phoenix® WinNonlin® (Version 8.1 or higher). 
Other parameters may be added as appropriate. 


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Pharmacokinetic analysis will use actual times as recorded on the eCRF. Other data handling 
procedures will be detailed in the Statistical Analysis Plan. 
8.5. 
Safety Analysis 
All AEs will be listed and treatment-emergent AEs will be summarized using the descriptive 
methodology. Each AE will be coded using the Medical Dictionary for Regulatory Activities. 
Observed values for clinical laboratory test data, 12-lead ECGs, vital signs, and physical 
examination findings will be listed.   
8.6. 
Interim Analysis 
No interim analyses are planned for this study.  
9. REFERENCES 
1. Suzhou Connect. CBP-307 – Investigator’s Brochure. (Version 6.0). December 2020. 
2. Avelox [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016. 
3. Darpo B, Benson C, Dota C, et al. Results from the IQ-CSRC prospective study support 
replacement of the thorough QT study by QT assessment in the early clinical phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
4. Ferber G, M Zhou, B Darpo. Detection of QTc effects in small studies--implications for 
replacing the thorough QT study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
5. Huang DP, Chen J, Dang Q, et al. Assay sensitivity in “Hybrid thorough QT/QTc (TQT)” 
study. Journal of Biopharmaceutical Statistics. 2019;29(2):378-384. 
6. Garnett C, Bonate PL, Dang Q , et al. Scientific white paper on concentration-QTc 
modeling. [Published correction appears in J Pharmacokinet Pharmacodyn. 
2018;45(3):399]. J Pharmacokinet Pharmacodyn. 2018;45(3):383-397. 
7. Tornøe CW, Garnett CE, Wang Y, et al. Creation of a knowledge management system for 
QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042. 
8. Cleveland WS. Robust Locally Weighted Regression and Smoothing Scatter Plots. 
J Amer Statist Assoc. 1979;74(368):829-836. 
9. Hurvich CM, Simonoff JS, Tsai CL. Smoothing parameter selection in nonparametric 
regression using an improved Akaike information criterion. J Roy Statist Soc Ser B Stat 
Methodol. 1998;60(2):27-193. 
 
 


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10. APPENDICES 


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Appendix 1: Adverse Event Reporting 
Definitions 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a study treatment, whether or not related to the study 
treatment. This includes any newly occurring event or previous condition that had increased 
in severity or frequency since the administration of study medication.  
Examples of AEs include: 
• Symptoms described by the subject, or signs observed by the investigator, and 
• Abnormal findings (involving clinically significant abnormal laboratory tests, ECG, 
etc.)  
• Exacerbation of previous condition, including increased incidence and/or severity. 
Note: Regarding decreased lymphocyte count in peripheral blood in this study, please report 
them as follows: 
• Since a decreased lymphocyte count in peripheral blood is due to the mechanism of 
action of the drug, it is not to be reported as an AE. However, clinical diagnosis 
related to a decreased lymphocyte count in peripheral blood indicates AE reporting (if 
no diagnosis is available, it is required to report related clinical symptoms or signs). 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs. All AEs will 
be recorded in the medical records and eCRFs. The investigator (or designee) is to record in 
detail any AE that occurred to the subject, including: AE diagnosis whenever possible, or 
signs, symptoms, the start date and time of occurrence, the stop date and time of occurrence, 
seriousness (ie, whether it is an SAE), severity of AEs, causality assessment, actions taken on 
the investigational product, other actions (eg, medications/treatments given), and outcomes of 
AEs.  
Assessment of Severity 
The investigator will be asked to provide an assessment of the severity of the AE using the 
following categories:  
• Mild: Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily 
living. 
• Moderate: Usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject. 


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• Severe: Interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
Relationship to Study Treatment 
The investigator (or designee) will make a determination of the relationship of the AE to the 
study treatment using a 4-category system according to the following guidelines: 
• Not Related: The AE is definitely caused by the subject’s clinical state or the study 
procedure/conditions. 
• Unlikely Related: The temporal association between the AE and the drug is such that 
the drug is not likely to have any reasonable association with the AE. 
• Possibly Related: The AE follows a reasonable temporal sequence from the time of 
drug administration but could have been produced by the subject’s clinical state or the 
study procedures/conditions. 
• Related: The AE follows a reasonable temporal sequence from the administration of 
the drug, abates upon discontinuation of the drug, follows a known or hypothesized 
cause-effect relationship, and (if appropriate) reappears when the drug is reintroduced.  
Follow-up of Adverse Events 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject 
who has an ongoing AE that is possibly related or related to the IMP or study procedures at 
the follow-up visit will be followed up, where possible, until resolution or until the 
unresolved AE is judged by the investigator (or designee) to have stabilized. This will be 
completed at the investigator’s (or designee’s) discretion. Any subject who has an ongoing 
AE that is not related or unlikely related to the IMP or study procedures at the follow-up visit 
can be closed out as ongoing at the investigator’s discretion.  
Adverse Drug Reactions 
All noxious and unintended responses to an IMP (ie, where a causal relationship between an 
IMP and an AE is at least a reasonable possibility) related to any dose should be considered 
adverse drug reactions. 
For marketed medicinal products, a response to a drug that is noxious and unintended and 
which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases 
or modification of physiological function is to be considered an adverse drug reaction. 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information (eg, IB for an unapproved 
IMP). 
Serious Adverse Events 
All SAEs will be collected after subjects sign the informed consent form and throughout the 
entire study, ie, until the end-of-study as specified in the protocol (or at early termination). 


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An SAE is defined as any untoward medical occurrence that at any dose either: 
• results in death 
• is life-threatening 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity (disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions) 
• results in a congenital anomaly/birth defect 
• results in an important medical event (see below). 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. 
Instances of death or congenital abnormality, if brought to the attention of the investigator at 
any time after cessation of the study treatment and considered by the investigator to be 
possibly related to the study treatment, will be reported to the sponsor (or designee). 
Definition of Life-threatening 
An AE is life-threatening if the subject was at immediate risk of death from the event as it 
occurred (ie, does not include a reaction that might have caused death if it had occurred in a 
more serious form). For instance, drug-induced hepatitis that resolved without evidence of 
hepatic failure would not be considered life-threatening even though drug-induced hepatitis 
can be fatal. 
Definition of Hospitalization 
Adverse events requiring hospitalization should be considered serious. In general, 
hospitalization signifies that the subject has been detained (usually involving an overnight 
stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate at the study site. When in doubt as to whether hospitalization occurred or 
was necessary, the AE should be considered as serious. 
Hospitalization for elective surgery or routine clinical procedures, which are not the result of 
an AE, need not be considered AEs and should be recorded on a clinical assessment form and 
added to the eCRF. If anything untoward is reported during the procedure, this must be 
reported as an AE and either ‘serious’ or ‘nonserious’ attributed according to the usual 
criteria. 
Serious Adverse Event Reporting 
The investigator will complete an SAE report form and forward it by facsimile or email to 
Covance APAC Drug Safety and the sponsor immediately (within 24 hours) upon becoming 
aware of an SAE. 


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All SAEs must be reported immediately (within 24 hours of discovery) to: +61-2-8879-2000 
SAE Reporting email: aeintake@covance.com (preferred method) 
Covance Safety SAE Reporting Fax Number: 61-2-6100-9788 or 1800-882-203 (toll free) 
 
The responsibilities of Covance APAC Drug Safety include the following: 
• Prepare an AE reporting plan prior to the start of the study. Where this plan differs 
from the applicable study site standard operating procedure on SAE reporting, the 
safety management plan will always take precedence. 
• Receive and review SAE report forms from the study site and inform the sponsor of 
the SAE within 1 working day of the initial notification to Covance APAC Drug 
Safety who will delete any information from the SAE report forms that may identify 
the subject. 
• Write case narratives and enter the case into Covance’s safety database as defined in 
the AE reporting plan. 
• Produce appropriate reports of all suspected unexpected serious adverse reactions and 
forward them to the EC, Medicines and Healthcare Products Regulatory Agency, 
principal investigator, and the sponsor within the timeframes stipulated in the Clinical 
Trials Directive Guideline (ENTR/CT 3).  
The responsibility for reporting SAEs will be transferred to the sponsor 28 days after the end 
of the study. 
For SAEs, the active reporting period to sponsor or its designated representative begins from 
the time that the subject provides informed consent through to the last subject visit.  
Nonserious AEs should be collected from the time the subject has taken the placebo dose on 
Day -1 through the last subject visit. If AEs that occur in the screening prior to the placebo 
administration to all subjects on Day -1 are considered to be related to the study procedure, 
they should be also collected.  
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subject will be questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, the 
sponsor should be notified within 24 hours of investigator awareness of the event. This time 
frame also applies to additional new information (follow-up) on previously forwarded SAE 
reports as well as to the initial and follow-up reporting of exposure during pregnancy.  
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his or her first awareness of the AE.  


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For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the time frames for reporting as specified above. In addition, an investigator 
may be requested by the sponsor to obtain specific additional follow-up information in an 
expedited fashion. This information collected for SAEs is more detailed than that captured on 
the AE eCRF. In general, this will include a description of the AE in sufficient detail to allow 
for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to the sponsor 
or its designated representative. 
Pregnancy 
Pregnancy (maternal or paternal exposure to study treatment) does not meet the definition of 
an AE. However, to fulfill regulatory requirements any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus. 
If the female subject becomes pregnant during the clinical trial and has not yet been dosed 
with study treatment, she must be withdrawn from the study. If the female subject becomes 
pregnant during the clinical trial and has been dosed, she must discontinue treatment 
immediately but may remain on study for safety evaluations. If the partner of a male subject 
becomes pregnant during the clinical trial, the subject can continue the clinical trial.  
For pregnancy of female subjects or partners of the male subjects during this study, 
investigators should report to the sponsor or designee in a pregnancy report form within 
24 hours after investigator awareness and report to the EC in time as per local requirement.  
The investigator will follow up on pregnancy outcomes, until not less than 12 months after 
birth, unless otherwise justified, and will report the outcome to the sponsor and ethics 
committee.  
If any adverse pregnancy outcome (eg, the outcome of the pregnancy is stillbirth, 
spontaneous abortion, or fetal malformations), it should be considered as an SAE and be 
reported in accordance with SAE reporting requirements. 
 
 


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Appendix 2: Clinical Laboratory Evaluations 
Clinical chemistry: 
Hematology: 
Urinalysis: 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Calcium 
Chloride 
Cholesterol 
Creatinine 
Direct bilirubina 
Gamma-glutamyl transferase 
Glucose 
Indirect bilirubina 
Inorganic phosphate  
Magnesium 
Potassium  
Sodium  
Total bilirubin 
Total protein 
Urea 
Uric acid 
Hematocrit  
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin 
concentration 
Mean cell volume 
Platelet count 
Red blood cell count 
White blood cell (WBC) count 
WBC differential: 
   Basophils 
   Eosinophils 
   Lymphocytes 
   Monocytes 
   Neutrophils 
 
Blood 
Glucose 
Ketones 
Leukocyte esterase  
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic examination  (if 
indicated by dipstick) 
Serology: 
Drug screen: 
Hormone panel - females 
only: 
Anti-hepatitis B surface antibody 
Anti-hepatitis B core antibody  
Hepatitis B surface antigen 
Hepatitis C antibody 
Human immunodeficiency (HIV-1 
and HIV-2) antibodies and p24 
antigen 
Syphilis 
Including but not limited to:  
Amphetamines/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine (metabolite) 
Methadone 
Phencyclidine 
Opiates 
Tetrahydrocannabinol 
Tricyclic antidepressants 
Cotinine test 
Follicle-stimulating hormone 
(postmenopausal females only) 
Serum pregnancy test (human 
chorionic gonadotropin)b 
Urine pregnancy testb  
Other Tests 
Low density lipoprotein cholesterol 
High-density lipoprotein 
cholesterol 
Triglycerides 
a Direct and indirect bilirubin will be analyzed if total bilirubin is elevated.  
b Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the 
follow-up visit (on Day 28±2 days). A positive urine pregnancy test will be confirmed with a serum pregnancy test.  


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Appendix 3: Total Blood Volume 
The following blood volumes will be withdrawn for each subject. 
Test 
Volume per blood 
sample (mL) 
Maximum number of 
blood samples 
Total amount of 
blood (mL) 
Clinical laboratory 
evaluations 
(including serology, 
syphilis, follicle-
stimulating hormone, and 
serum pregnancy tests) 
12.5 
5 
62.5 
CBP-307/Moxifloxacin 
Pharmacokinetics 
(includes discard volume 
per draw) 
8 
40 
320 
Total: 
382.5 
If extra blood samples are required, the maximum blood volume to be withdrawn per subject 
will not exceed 500 mL. 


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Appendix 4: Contraception Guidance 
Definitions 
Women of Childbearing Potential: premenopausal females who are anatomically and 
physiologically capable of becoming pregnant following menarche. 
Women of Nonchildbearing Potential:  
1. Surgically sterile: females who are permanently sterile via hysterectomy, 
bilateral salpingectomy, and/or bilateral oophorectomy by reported medical 
history and/or medical records. Surgical sterilization to have occurred a minimum 
of 6 weeks, or at the investigator’s discretion, prior to screening. 
2. Postmenopausal: females at least 45 years of age with amenorrhea for 12 months 
without an alternative medical reason with confirmatory follicle-stimulating 
hormone (FSH) levels of ≥40 mIU/mL. The amenorrhea should not be induced by 
a medical condition such as anorexia nervosa, hypothyroid disease or polycystic 
ovarian disease, or by extreme exercise. It should not be due to concomitant 
medications that may have induced the amenorrhea such as oral contraceptives, 
hormones, gonadotropin-releasing hormones, anti-estrogens, or selective estrogen 
receptor modulators. Females on hormone replacement therapy with FSH levels 
<40 mIU/mL may be included at the discretion of the investigator.   
Fertile male: a male that is considered fertile after puberty. 
Infertile male: permanently sterile male via bilateral orchiectomy. 
Contraception Guidance 
Female Subjects 
Female subjects who are of nonchildbearing potential will not be required to use 
contraception. Female subjects of childbearing potential must be willing to use 2 methods 
(1 primary and 1 secondary method) of birth control from the time of signing the ICF until 
90 days after the follow-up visit. Primary (non-barrier) methods of contraception include: 
• surgical method performed at least 3 months prior to the screening visit: 
o 
bilateral tubal ligation or bilateral salpingectomy 
o 
Essure® (hysteroscopic bilateral tubal occlusion) with confirmation of 
occlusion of the fallopian tubes 
• non-hormonal intrauterine device or Mirena® (other hormonal intrauterine devices 
will not be allowed) in place for at least 3 months prior to the first dose of the study 
drug 
• vasectomized male partner (sterilization performed at least 90 days prior to the 
screening visit, with verbal confirmation of surgical success, and the sole partner for 
the female subject)  


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Secondary (barrier) methods of contraception include: 
• male condom without spermicide 
• female condom without spermicide 
• cervical cap without spermicide (as prescribed) 
• diaphragm without spermicide (as prescribed). 
Female subjects of childbearing potential should refrain from donation of ova from check-in 
(Day -2) until 90 days after the follow-up visit. 
Male Subjects 
Male subjects (even with a history of vasectomy) with partners of childbearing potential must 
use a male barrier method of contraception (ie, male condom without spermicide) in addition 
to a second method of acceptable contraception from check-in until 90 days after the 
follow-up visit. Acceptable methods of contraception for female partners include: 
• hormonal injection 
• combined oral contraceptive pill or progestin/progestogen-only pill 
• combined hormonal patch 
• combined hormonal vaginal ring 
• surgical method (bilateral tubal ligation or Essure® [hysteroscopic bilateral tubal 
occlusion])  
• hormonal implant 
• hormonal or non-hormonal intrauterine device 
• cervical cap without spermicide 
• diaphragm without spermicide. 
An acceptable second method of contraception for male subjects is vasectomy that has been 
performed at least 90 days prior to the screening visit with verbal confirmation of surgical 
success. 
For male subjects (even with a history of vasectomy), sexual intercourse with female partners 
who are pregnant or breastfeeding should be avoided unless condoms are used from the time 
of the first dose until 90 days after the follow-up visit. Male subjects are required to refrain 
from donation of sperm from check-in until 90 days after the follow-up visit. 
Sexual Abstinence and Same-sex Relationships 
Subjects who practice true abstinence, because of the subject’s lifestyle choice (ie, the subject 
should not become abstinent just for the purpose of study participation), are exempt from 
contraceptive requirements. Periodic abstinence (eg, calendar, ovulation, symptothermal, 
postovulation methods) and withdrawal are not acceptable methods of contraception. If a 


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subject who is abstinent at the time of signing the ICF becomes sexually active they must 
agree to use contraception as described previously.  
For subjects who are exclusively in same-sex relationships, contraceptive requirements do not 
apply. If a subject who is in a same-sex relationship at the time of signing the ICF becomes 
engaged in a heterosexual relationship, they must agree to use contraception as described 
previously. 


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Appendix 5: Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol, local legal and regulatory 
requirements and with the following: 
• General principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), Guidelines for good clinical practice (GCP) (ICH 1996), and 
the Declaration of Helsinki (World Medical Association 2008).  
• Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents must be 
submitted to the human research ethics committee (HREC) by the investigator and reviewed 
and approved by the HREC before the study is initiated.  
Any protocol amendments will require EC approval before implementation of changes made 
to the study design, except for changes necessary to eliminate an immediate hazard to study 
subjects.  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents from the 
HREC. All correspondence with HREC should be retained in the investigator file. A copy of 
HREC approval should be forwarded to the sponsor. 
• The investigator will be responsible for the following:  
• Providing written summaries of the status of the study to the EC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the EC.  
• Notifying the EC of SAEs or other significant safety findings as required by EC 
procedures.  
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of ICH guidelines, the EC, and all other applicable local regulations.  
Regulatory Authority  
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency 
in accordance with any applicable country-specific regulatory requirements before the study 
is initiated at a study center in that country. 
Finances and Insurance 
Financing and insurance will be addressed in a separate agreement. 


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Informed Consent 
Prior to starting participation in the study, each subject will be provided with a study-specific 
ICF giving details of the study treatments, procedures, and potential risks of the study. 
Subjects will be instructed that they are free to obtain further information from the 
investigator (or designee) and that their participation is voluntary and they are free to 
withdraw from the study at any time. Subjects will be given an opportunity to ask questions 
about the study prior to providing consent for participation. 
Following the discussion of the study with study site personnel, subjects will sign the ICF in 
the presence of a suitably trained member of staff to indicate that they are freely giving their 
informed consent. A copy of the ICF will be given to the subject. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
Subject Data Protection 
Subjects will be assigned a unique identifier and will not be identified by name in eCRFs, 
study-related forms, study reports, or any related publications. Subject and investigator 
personal data will be treated in compliance with all applicable laws and regulations. In the 
event the study protocol, study report, or study data are included in a public registry, all 
identifiable information from individual subjects or investigators will be redacted according 
to applicable laws and regulations.  
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. The subject must also be informed that his/her study-related data 
may be examined by sponsor or contract research organization (CRO) auditors or other 
authorized personnel appointed by the sponsor, by appropriate EC members, and by 
inspectors from regulatory authorities. 
Disclosure 
All information provided regarding the study, as well as all information collected and/or 
documented during the course of the study, will be regarded as confidential. The investigator 
(or designee) agrees not to disclose such information in any way without prior written 
permission from the sponsor. 
Data Quality Assurance 
The following data quality steps will be implemented: 
• All relevant subject data relating to the study will be recorded on eCRFs unless 
directly transmitted to the sponsor or designee electronically (eg, laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the eCRF.  


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• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
• The investigator must permit study-related monitoring, audits, EC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Predefined agreed risks, monitoring thresholds, 
quality tolerance thresholds, controls, and mitigation plans will be documented in a 
risk management register. Additional details of quality checking to be performed on 
the data may be included in a data management plan.  
• A study monitor will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator in the study site archive for at least 5 years after 
the end of the study unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
Investigator Documentation Responsibilities 
All individual, subject-specific study data will also be entered into a 21 Code of Federal 
Regulations Part 11-compliant electronic data capture (EDC) system on an eCRF in a timely 
fashion. 
All data generated from external sources (eg, laboratory and bioanalytical data), and 
transmitted to the sponsor or designee electronically, will be integrated with the subject’s 
eCRF data in accordance with the data management plan.  
An eCRF must be completed for each enrolled subject who undergoes any screening 
procedures, according to the eCRF completion instructions. The sponsor, or CRO, will 
review the supporting source documentation against the data entered into the eCRFs to verify 
the accuracy of the electronic data. The investigator will ensure that corrections are made to 
the eCRFs and that data queries are resolved in a timely fashion by the study staff. 
The investigator will sign and date the eCRF via the EDC system’s electronic signature 
procedure. These signatures will indicate that the investigator reviewed and approved the data 
on the eCRF, data queries, and site notifications. 
Publications 
Publications will be addressed as follows:The results of this study may be published or 
presented at scientific meetings. If this is foreseen, the investigator agrees to submit all 


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manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect 
proprietary information and provide comments. 
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support the publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by 
mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 


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Appendix 6: Schedule of Assessments 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-up 
Visit 
Study Day(s) 
-28 to -3
-2
-1
1 
2 to 4 
5 
6 to 13 
14 
15 
16 
28±2 
Informed consent 
X 
Eligibility criteria review 
(Inclusion/Exclusion) 
X 
X 
Demographics 
X 
Medical history 
X 
Admission to clinical research unit1 
X 
Discharge from clinical research 
unit2  
X 
Randomization 
X 
Vital signs3,8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height/weight/BMI 
X 
Physical exam 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
Clinical chemistry  
(including cholesterol panel tests) 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Serology for HIV-1/HIV-2 
antibodies and p24 antigen, HBsAb, 
HBcAb, HBsAg, or HCVAb 
X 
12-lead safety electrocardiogram4,8
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breath alcohol, urine drug toxicology 
and cotinine  
X 
X 
Cardiodynamic monitoring 
(Holter)/replicate ECG extraction5 
X 
X 
X 
X 
X 
Pregnancy test6 
X 
X 
X 


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Schedule of Assessments 
Study Period 
Screening 
In-house Treatment Period 
End-of-
Study/Follow-up 
Visit 
Study Day(s) 
-28 to -3 
-2 
-1 
1 
2 to 4 
5 
6 to 13 
14 
15 
16 
28±2 
Follicle -stimulating hormone test 
(postmenopausal females only) 
X 
 
 
 
 
 
 
 
 
 
 
CBP-307/placebo administration 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
Moxifloxacin/placebo administration 
 
 
 
X 
 
 
 
 
X 
 
 
Blood sampling for PK7,8 
 
 
 
X 
 
X 
 
X 
X 
 
 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; ECG = electrocardiogram; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibodies; HIV = human 
immunodeficiency virus; PK = pharmacokinetic. 
1. Subjects will be asked to arrive at the clinical site in the afternoon 2 days before start of dosing on Day 1 (Day -2).  
2. Discharge from unit will occur after the 24-hour PK samples and after completion of safety assessments on Day 16. 
3. Screening and Check-in on Day -2:  Tympanic temperature, respiratory rate, and supine pulse rate and blood pressure. Other days (except for Day 16): Prior to and 
2 hours after dosing, supine vital signs (tympanic temperature, pulse rate, respiratory rate, and blood pressure). Discharge (Day 16): Prior to discharge, supine vital signs 
(tympanic temperature, pulse rate, respiratory rate, and blood pressure). End of Study/Follow-up Visit (Day 28±2 days): Tympanic temperature, respiratory rate, and 
supine pulse rate and blood pressure. 
4. 12-lead safety ECG will be recorded in triplicates before dosing and in singles 2 hours postdose on all study days and before discharge on Day 16. Postdose safety will be 
interpreted on-site by the investigator and may be repeated to confirm/refute clinically abnormal findings.  
5. Continuous cardiodynamic monitoring (Holter) will be performed for 25 hours on Day -1 (baseline), 1, 5, 14, and 15. The recording will be started at least 1 hour before 
dosing and at the corresponding clock time on Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 1, 
2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. At timepoints for ECG extractions, subjects will be supinely resting in an undisturbed environment. When timepoints 
for ECG extraction, safety ECGs, vital signs assessment, and blood draws coincide, procedures will be performed in this order. The ECG effects of CBP-307 will be 
tested on data from Day -1 (baseline for both groups), Day 5 (therapeutic concentrations versus placebo), and Day 14 (supratherapeutic concentrations versus placebo). 
Assay sensitivity with moxifloxacin will be tested on data from Days -1, 1, 14, and 15. 
6. Serum pregnancy test will be performed at screening and urine pregnancy tests will be performed on Day -2 and at the follow-up visit (Day 28±2 days). A positive urine 
pregnancy test will be confirmed with a serum pregnancy test. 
7. Pharmacokinetic samplings will be performed prior to dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 5, 14, and 15). 
8. Allowable assessment/sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours 
postdose, and ±30 minutes for 12 to 24 hours postdose. 

SAP_001.pdf: 
Clinical Study Report 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002  
 
16.1.9. 
Documentation of Statistical Methods 
16.1.9.1. 
Statistical Analysis Plan 


TITLE PAGE 
Statistical Analysis Plan 
A Phase I, Multicenter, Randomized, Double-blind, Double-dummy, 
Placebo- and Positive-Controlled Study to Investigate the Effects of CBP-
307 on the QTC Interval in Healthy Subjects 
SAP Status: Final 
SAP Version: 2.0 
SAP Date: 10May2022 
Investigational Medicinal Product: CBP-307 
Protocol Reference: CBP-307AU002 (Protocol Version 5.0) 
Labcorp Study: 8463245 
Sponsor: 
Connect Biopharma Australia Pty Ltd. 
737 Burwood Road 
Suite 312 
Hawthorn East, Victoria 3123 
Australia 
Study Sites: 
CMAX 
Level 5/18a North Terrace 
Adelaide, South Australia 5000 
Australia 
Clinical Pharmacology of Miami (CPMI), 
LLC 
550 West 84th Street 
Hialeah, Florida 33014 
United States 
Principal Investigator: 
Nicholas Farinola, MBBS 
Juan Carlos Rondon, MD, JD, CPI, FCLM 
Information described herein is confidential and may be disclosed only with the express 
written permission of the sponsor. 


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TABLE OF CONTENTS 
TITLE PAGE ..................................................................................................................... 1 
TABLE OF CONTENTS .................................................................................................... 2 
LIST OF IN-TEXT TABLES AND FIGURES .................................................................... 3 
LIST OF ABBREVIATIONS ............................................................................................. 4 
1. INTRODUCTION .......................................................................................................... 5 
2. STUDY OBJECTIVES ................................................................................................... 5 
3. STUDY ENDPOINTS .................................................................................................... 6 
4. STUDY DESIGN ........................................................................................................... 7 
5. SAMPLE SIZE JUSTIFICATION .................................................................................10 
6. STUDY TREATMENTS ...............................................................................................11 
7. DEFINITIONS OF POPULATIONS..............................................................................12 
7.1. All Subjects Population ...........................................................................................12 
7.2. Safety Population ....................................................................................................12 
7.3. Pharmacokinetic Population.....................................................................................13 
7.4. Cardiodynamic Population .......................................................................................13 
8. STATISTICAL METHODOLOGY................................................................................13 
8.1. General ...................................................................................................................13 
8.1.1. Handling of Data Quality Issues Due to Coronavirus Disease 2019 and Related 
Restrictions ................................................................................................................13 
8.1.2. Calculation of the Summary Statistics ................................................................14 
8.1.3. Triplicate Readings ...........................................................................................15 
8.1.4. Repeat and Unscheduled Readings.....................................................................15 
8.1.5. Definitions of Baseline and Change from Baseline .............................................15 
8.2. Subject Disposition and Population Assignment .......................................................16 
8.3. Screening Demographics and Baseline Characteristics ..............................................16 
8.4. Prior and Concomitant Medication ...........................................................................16 
8.5. Pharmacokinetic Assessments ..................................................................................16 
8.5.1. Pharmacokinetic Analysis .................................................................................16 
8.5.2. Presentation of Pharmacokinetic Data ................................................................19 
8.5.3. Pharmacokinetic Statistical Methodology...........................................................19 
8.6. Safety and Tolerability Assessments ........................................................................20 
8.6.1. Adverse Events .................................................................................................20 


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8.6.2. Clinical Laboratory Parameters..........................................................................22 
8.6.3. Vital Signs Parameters ......................................................................................22 
8.6.4. Safety 12-lead Electrocardiogram Parameters.....................................................22 
8.6.5. Cardiac Telemetry Monitoring...........................................................................23 
8.6.6. Other Assessments ............................................................................................23 
8.6.7. Safety and Tolerability Statistical Methodology .................................................23 
9. INTERIM ANALYSES .................................................................................................23 
10. SIGNIFICANT CHANGES FROM THE PROTOCOL-SPECIFIED ANALYSES ........23 
11. REFERENCES ............................................................................................................23 
12. APPENDICES .............................................................................................................25 
Appendix 1: 
Document History............................................................................25 
 
LIST OF IN-TEXT TABLES AND FIGURES 
Table 1: 
Presentation of Study Treatments in TFLs ........................................................11 
Table 2: 
Presentation of Study Treatment Sequences in TFLs .........................................12 
 
Figure 1: 
Study Design .................................................................................................... 8 
 


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LIST OF ABBREVIATIONS 
Abbreviations pertain to the statistical analysis plan (SAP) only (not the tables, figures, and 
listings [TFLs]).  
ADaM 
Analysis Data Model 
AE 
adverse event 
AUC0-24 
area under the concentration-time curve from time zero to 24 hours 
postdose 
AUCinf 
area under the concentration‑time curve from time zero extrapolated to 
infinity 
BLQ 
below the limit of quantification 
CDISC 
Clinical Data Interchange Standards Consortium 
Cmax 
maximum observed concentration 
COVID-19 
coronavirus disease 2019 
CSR 
clinical study report 
DMP 
data management plan 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOS 
end of study 
HR 
heart rate 
ICF 
informed consent form 
ICH 
International Council for/Conference on Harmonisation 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetic(s) 
PR 
pulse rate 
QTc 
heart-rate corrected QT interval 
QTcB 
QT interval corrected for heart rate using Bazett’s formula 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
SAP 
statistical analysis plan 
SD 
standard deviation 
SDV 
source document verification 
TEAE 
treatment-emergent adverse event 
TFL 
table, figure, and listing 
tmax 
time of the maximum observed concentration 
WHODrug 
World Health Organization Drug Dictionary  
Δ 
change-from-baseline 
ΔΔ 
placebo-corrected or placebo-adjusted change-from-baseline 


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1. INTRODUCTION 
This SAP has been developed after review of the clinical study protocol Amendment 4 
(Protocol Version 5.0 dated 12 January 2022) and electronic case report form (eCRF).  
This SAP describes the planned analysis of the pharmacokinetic (PK), safety, and tolerability 
data from this study. A detailed description of the planned TFLs to be presented in the 
clinical study report (CSR) is provided in the accompanying TFL shells document.  
In general, the analyses are based on information from the protocol, unless they have been 
modified by agreement with Connect Biopharma Australia Pty Ltd. A limited amount of 
information about this study (eg, objectives, study design) is given to help the reader’s 
interpretation.  
This SAP must be finalized prior to any unblinding of study data. Additionally, the SAP and 
TFL shells should be finalized prior to any programming activities commencing.  
This SAP supersedes any statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed 
and will be identified accordingly in the CSR. Any substantial deviations from this SAP will 
be agreed with Connect Biopharma Australia Pty Ltd. and identified in the CSR.  
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E3 guideline Structure and Content of Clinical Study 
Reports, ICH E8 guideline General Considerations for Clinical Trials, ICH E9 guideline 
Statistical Principles for Clinical Trials.1,2,3  
The document history is presented in Appendix 1.  
2. STUDY OBJECTIVES  
The primary objective of the study is: 
• To evaluate the effects of therapeutic and supratherapeutic CBP-307 plasma concentrations 
on the heart-rate corrected QT interval (QTc) in healthy subjects. 
The secondary objectives of the study are: 
• To demonstrate assay sensitivity of the study to detect a small QT effect using moxifloxacin 
as a positive control. 
• To evaluate the safety and tolerability of therapeutic and supratherapeutic multiple oral 
doses of CBP-307 in healthy subjects. 
• To assess the pharmacokinetics (PK) of CBP-307 following administration of therapeutic 
and supratherapeutic multiple oral doses in healthy subjects. 


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• To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of CBP-307 
on heart rate (HR), pulse rate (PR) and QRS intervals, and T-wave morphology.  
Note: This SAP only focuses on the PK, safety and tolerability objectives. All QTc related 
objectives will be covered in a separate report provided by ERT Inc. 
3. STUDY ENDPOINTS  
Electrocardiogram Endpoints: 
The primary endpoint is the change-from-baseline QTcF (ΔQTcF). 
The secondary endpoints are: 
• Change-from-baseline HR, PR, QRS (ΔHR, ΔPR, and ΔQRS); 
• Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (ΔΔHR, ΔΔQTcF, 
ΔΔPR, and ΔΔQRS); 
• Categorical outliers for QTcF, HR, PR, and QRS; 
• Frequency of treatment-emergent changes of T- wave morphology and U-wave 
presence. 
Pharmacokinetic Endpoints: 
• area under the concentration‑time curve from time zero extrapolated to infinity 
(AUCinf) 
• area under the concentration-time curve from time zero to 24 hours postdose 
(AUC0-24) 
• maximum observed concentration (Cmax) 
• time of the maximum observed concentration (tmax) 
Other PK parameters may also be reported. 
Safety Endpoints: 
The safety outcome measures for this study are as follows: 
• incidence and severity of AEs 
• incidence of laboratory abnormalities, based on hematology, clinical chemistry, and 


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urinalysis test results 
• 12-lead ECG parameters 
• vital signs measurements. 
Note: This SAP only focuses on the PK, safety and tolerability endpoints. All QTc related 
endpoints will be covered in a separate report provided by ERT Inc. 
4. STUDY DESIGN  
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, 
positive-controlled, multi-site, 3-arm study to investigate the effects of therapeutic and 
supratherapeutic oral doses of CBP-307 on the QTc interval in healthy male and female 
subjects. 
Potential subjects will be asked to read and sign an informed consent form (ICF). After 
informed consent is obtained, screening procedures and tests to establish subject eligibility to 
enter the study will be performed within 28 days before Day 1. After informed consent has 
been obtained but prior to the initiation of study treatment administration, only SAEs will be 
reported. After placebo administration to all subjects on Day -1, all AEs, whether 
volunteered, elicited, or noted upon physical examination, will be recorded throughout the 
study (ie, from Day -1 until the end of the study). 
In this study, approximately 68 healthy subjects (at least 30% for each sex) will be 
randomized into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 
2 sub-groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Randomized subjects will receive the assigned study drug as a single dose in the morning on 
Days 1, 2, 3 to 6, 7 to 15, and on Day 16 (placebo will be administered to all subjects on Day 
-1). 
The following treatments will be administered: 
• Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated dose 
of 0.1 mg on Day 2) 
• A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6) 
• A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15) 
• Placebo (matched to moxifloxacin and CBP-307) 
• Moxifloxacin (400 mg) 
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ΔΔQTcF) 
of 10 to 15 msec. 
A summary of dosing timelines per Group is shown below: 


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Study Treatment 
Name 
Treatment 
Group 
CBP-307 
CBP-307 
Matched 
Placebo 
Moxifloxacin 
(Avelox) 
Moxifloxacin 
Matched 
Placebo 
Dosage 
Formulation 
Capsule 
Capsule 
Tablet 
Tablet 
Unit Dose 
Strength(s)/Level(s) 
0.05 mg 
0.1 mg 
Not applicable 
400 mg 
Not applicable 
Dosage Frequency 
Day -1 Group 1 
1 capsule 
Group 2A 
1 capsule 
Group 2B 
1 capsule 
Day 1 Group 1 
1 × 0.05 mg 
1 tablet 
Group 2A 
1 capsule 
1 × 400 mg 
Group 2B 
1 capsule 
1 tablet 
Day 2 Group 1 
1 × 0.1 mg 
Group 2A 
1 capsule 
Group 2B 
1 capsule 
Days 3 to 6 Group 1 
2 × 0.1 mg 
Group 2A 
2 capsules 
Group 2B 
2 capsules 
Days 7 to 15 Group 1 
5 × 0.1 mg 
Group 2A 
5 capsules 
Group 2B 
5 capsules 
Day 16 Group 1 
1 capsule 
1 tablet 
Group 2A 
1 capsule 
1 tablet 
Group 2B 
1 capsule 
1 × 400 mg 
A schematic of the study design is presented in 
Figure 1.  
Figure 1: 
Study Design  


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Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 
(or on Day -4 depending on the clinical site’s requirement for Coronavirus Disease 2019 
[COVID-19] testing) and will remain at the study site until discharge on Day 19. Treatment 
administration will occur on Days 1, 2, 3 to 6, 7 to 15, and 16 under fasting conditions (all 
subjects will receive placebo on Day -1). Continuous cardiodynamic ECG monitoring and 
recording will begin at least 25 hours prior to the administration of study treatments on Day 1 
and continue through 24 hours after the administration of study treatments on Days 1, 6, 15, 
and 16 and at corresponding timepoints on the day before dosing, ie, Day -1. Blood samples 
for PK analysis will be collected predose and at each postdose cardiodynamic ECG 
timepoint. Additional PK samples will be collected at 72 and 96 hours following dosing on 
Day 15. Subjects will return to the study site for a follow-up visit on Day 29±2 days.  
Baseline for the primary analysis will be determined from predose timepoints collected for 25 
hours on Day -1 (prior to administration of study treatments on Day 1). Continuous 
cardiodynamic monitoring (Holter) will be performed for 25 hours on Days -1, 1, 6, 15, and 
16. The recording will be started 1 hour before dosing and at the corresponding clock time on 
Day -1. Replicate 12-lead ECGs will be extracted from the continuous recording prior to 
dosing (-30 minutes) and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose on each day. 
Pharmacokinetic blood samples will be collected at the following timepoints: prior to dosing 
and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day (Days 1, 6, 
15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours postdose, ±5 
minutes for 1 to 4 hours postdose, ±10 minutes for 6 to 8 hours postdose, and ±30 minutes for 
12 to 24 hours postdose). Additional PK samples will be collected at 72 and 96 hours 
following dosing on Day 15 (sample collection window: ±30 minutes). Subjects will be 
inactive and in a supine position for at least 10 minutes prior to and 5 minutes after each 
cardiodynamic ECG extraction timepoint, which will end immediately prior to the PK 
sampling. At each timepoint, up to 10 ECG replicates will be extracted from a 5-minute time 
window (the last 5 minutes of the 15-minute period when the subject is maintained in a 
supine, quiet position). The ECG effects of CBP-307 will be tested on data from Day -1 
(baseline for both groups), Day 6 (therapeutic concentrations versus placebo), and Day 15 


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(supratherapeutic concentrations versus placebo). Assay sensitivity with moxifloxacin will be 
evaluated using ECG data collected on Days -1, 1, 15, and 16. 
The central ECG laboratory (eResearch Technology Inc., Philadelphia, PA) will be blinded to 
treatment. The continuous 12-lead digital ECG data will be exported from the system and 
sent to the central ECG laboratory for review. Resting ECGs to be used in the analyses will 
be selected from predetermined timepoints specified above and will be read by the central 
ECG laboratory. 
Safety assessments including AEs, vital signs, clinical laboratory tests, safety 12-lead ECGs, 
and physical examination findings will be performed at screening and at specific timepoints 
during the study, and/or at the follow-up visit. In addition, subjects will be monitored via 
cardiac telemetry at specific timepoints during the treatment period. 
The total duration of study participation for each subject (from screening through follow-up 
visit) is anticipated to be approximately 59 days. 
The start of the study is defined as the date the first subject signs an ICF. The point of 
enrollment occurs at the time of subject number allocation. The end of the study is defined as 
the date of the last subject’s last assessment (scheduled or unscheduled). 
 
5. SAMPLE SIZE JUSTIFICATION  
Approximately 64 healthy subjects (at least 30% for each sex) will be randomized into 2 
groups (Group 1 and 2) with 32 subjects in each. Group 2 consists of 2 sub-groups (Group 2A 
and 2B) and each sub-group will be randomized with 16 subjects. 
Sample Size for Primary Analysis: 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-msec QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-307 
in the study. This power is estimated approximately using a 2-sample t-test. The calculation 
assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 3 msec and a 
standard deviation (SD) of the ΔQTcF of 8 msec for both CBP-307 and placebo treatment 
groups. Note that this calculation is conservative, since it does not take into account any gain 
in precision due to the use of all data of each subject with the help of a linear mixed-effects 
model. The concentration-QTc analysis method is supported by Darpo et al 20154 and Ferber 
et al, 2015,5 and consistent with the experiences from 25 recent TQT studies. 
Sample Size Considerations for Assay Sensitivity: 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that the 
ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 msec (ie, the lower bound of the 
2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 msec). In a similarly 
designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the standard 
error (SE) for the prediction of the QT effect of moxifloxacin based on the exposure-response 


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analysis was 1.24 msec. The within-subject SD of ΔQTcF in the referred study was 5.4 msec 
based on the by-timepoint analysis. If the effect of moxifloxacin is assumed to be 10 msec, 
the SE of 1.24 msec corresponds to an effect size of (10-5)/(1.24×sqrt[24])=0.82, where the 
effect size is the effect assumed under the alternative hypothesis divided by the SD of the test 
variable. This value should be compared to the effect size of 0.64 required to guarantee a 
power of at least 95% in a paired t-test situation with a sample size of 28 evaluable subjects. 
In other words, based on this calculation, a power of at least 95% will be obtained as long as 
the variability of the ΔQTcF, as measured by its within-subject SD from the by-timepoint 
analysis, does not exceed 6.9 msec (ie, 128% [= 0.82/0.64] of the 5.4 msec observed in the 
referred study assuming the ratio of effective sizes is consistent with inverse ratio of within-
subject SD). The number also agrees with recent recommendations of the FDA, which 
propose at least 20 subjects.6 
6. STUDY TREATMENTS
The study treatment names and ordering to be used in the TFLs are presented in Table 1. 
Table 1: 
Presentation of Study Treatments in TFLs  
Study Treatment 
Order in TFLs 
Placebo 
1 
400 mg Moxifloxacin 
2 
0.05 mg CBP-307 
3 
0.1 mg CBP-307 
4 
0.2 mg CBP-307 
5 
0.5 mg CBP-307 
6 
All TFLs will be based on actual treatments (eg, if subject was assigned to receive placebo 
but was wrongfully dosed with active treatment they would be summarized and listed under 
active treatment). 
The study treatment sequence names, abbreviations, and ordering to be used in the TFLs 
are presented in Table 2.  


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Table 2: 
Presentation of Study Treatment Sequences in TFLs 
Study Treatment Sequence 
Abbreviation 
Order in
TFLs 
1 capsule of CBP-307 matched placebo on Day -1 -> 1 × 
0.05 mg CBP-307 and 1 tablet of Moxifloxacin matched 
placebo on Day 1 -> 1 × 0.1 mg CBP-307 on Day 2 -> 2 × 
0.1 mg CBP-307 on Days 3 to 6 -> 5 × 0.1 mg CBP-307 on 
Days 7 to 15 -> 1 capsule of CBP-307 matched placebo 
and 1 tablet of Moxifloxacin matched placebo on Day 16 
Group 1 
1 
1 capsule of CBP-307 matched placebo on Day -1 -> 1 
capsule of CBP-307 matched Placebo and 1 × 400 mg 
Moxifloxacin tablet on Day 1 -> 1 capsule of CBP-307 
matched Placebo on Day 2 -> 2 capsules of CBP-307 
matched Placebo Days 3 to 6 -> 5 capsules of CBP-307 
matched Placebo on Days 7 to 15 -> 1 capsule of CBP-307 
matched placebo and 1 tablet of Moxifloxacin matched 
placebo on Day 16 
Group 2A 
2 
1 capsule of CBP-307 matched placebo on Day -1 -> 1 
capsule of CBP-307 matched Placebo and 1 tablet of 
Moxifloxacin matched placebo on Day 1 -> 1 capsule of 
CBP-307 matched Placebo on Day 2 -> 2 capsules of CBP-
307 matched Placebo Days 3 to 6 -> 5 capsules of CBP-
307 matched Placebo on Days 7 to 15 -> 1 capsule of CBP-
307 matched placebo and 1 × 400 mg Moxifloxacin tablet 
on Day 16 
Group 2B 
3 
The summaries will be based on planned treatment sequences and listings will be based on 
actual treatment and sequences. 
7. DEFINITIONS OF POPULATIONS
Any protocol deviations, including those due to coronavirus disease 2019 (COVID-19) 
and related restrictions (see Section 8.1.1), will be considered prior to database lock for 
their importance and taken into consideration when assigning subjects to populations. 
7.1. All Subjects Population 
The all subjects population will include all subjects who signed the informed consent form 
and had any study assessment recorded in the database per the protocol.  
7.2. Safety Population 
The safety population will include all subjects who received at least 1 dose of investigational 
product drug starting from Day -1 (therapeutic and supratherapeutic doses of CBP-307, 
moxifloxacin, or placebo).  


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7.3. Pharmacokinetic Population  
The PK population will include all subjects who received at least 1 dose of investigational 
product and have evaluable PK data of any of the analytes (CBP-307 and moxifloxacin). A 
subject may be excluded from the PK summary statistics and statistical analysis if the subject 
has an AE of vomiting that occurs at or before 2 times median time to maximum 
concentration.  
7.4. Cardiodynamic Population  
The cardiodynamic population will be specified in the report from ERT Inc. and not included 
in this SAP. 
8. STATISTICAL METHODOLOGY  
8.1. General  
Listings will be provided for all data captured in the database, including medical history. 
Listings will include all subjects assigned to the all subjects population and include data up to 
the point of study completion or discontinuation. Subjects are generally considered to have 
completed the study if they complete the scheduled follow-up visit (rather than early 
termination visit). Any subject who discontinues the study will be identified accordingly in 
the listings. Summaries and statistical analyses will include the subjects assigned to the 
relevant population based on data type.  
Data analysis will be performed using the SAS® statistical software package Version 9.4 (or 
higher if a new version is issued during the study).  
Analysis Data Model (ADaM) datasets will be prepared using Clinical Data Interchange 
Standards Consortium (CDISC) ADaM Version 2.1 (or higher if a new version is issued 
during the study) and CDISC ADaM Implementation Guide Version 1.1 (or higher if a new 
version is issued during the study). Pinnacle 21 Community Validator Version 3.1.0 (or 
higher if a new version is issued during the study) will be utilized to ensure compliance with 
CDISC standards.  
Where reference is made to ‘valid’ data, this refers to non-missing data which meet the 
predetermined criteria (eg, are not flagged for exclusion).  
Where reference is made to ‘all calculations’, this includes, but is not limited to, summary 
statistics, statistical analyses, baseline derivation and changes from baseline.  
All figures will be produced on linear-linear or discrete-linear scales, as applicable, unless 
specifically stated otherwise. 
8.1.1. Handling of Data Quality Issues Due to Coronavirus Disease 2019 and Related 
Restrictions 
Due to COVID-19 and related restrictions, there is a high risk for impact to data integrity, 
with the recognized potential for: 


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● Missed visits, caused by, for example,: 
o Subject unable to travel to site due to restrictions, the need to quarantine, or 
COVID-19 infection 
o Subject unwilling to go to site due to fear of COVID-19 infection 
o Site postponing subject’s visit due to investigator not being available (eg, if they 
have been dispatched to hospital handling COVID-19 infections) 
● Site unable to replenish supply of investigational product 
● Incomplete data entry by sites due to limited resources to support study or no access 
to source documents or to eCRF 
● Outstanding source document verification (SDV) due to sponsor or country 
restrictions on remote SDV, or no or limited access to site(s) for on-site visits 
● Unanswered queries 
At the time of the reporting of the study results, all protocol deviations due to COVID-19 or 
related restriction will be assessed for their severity and impact on the analyses. If needed, 
appropriate statistical methods will be applied as a mitigating action (eg, data might be 
categorized into 2 analysis groups, with and without COVID-19 and related restrictions 
impact); however, this will exclude any imputations of the missing values. Any mitigating 
actions will be agreed with Connect Biopharma Australia Pty Ltd in advance and identified in 
the CSR.  
8.1.2. Calculation of the Summary Statistics  
For continuous data the following rules will be applied:  
● Missing values will not be imputed, unless specifically stated otherwise.  
● Unrounded data will be used in the calculation of summary statistics.  
● If the number of subjects with valid observations (n) <3, summary statistics will not 
be calculated, with the exception of n, minimum, and maximum.  
● In general, as early termination data are not associated with any scheduled timepoint, 
they will be excluded from all calculations of summary statistics and statistical 
analyses. Exceptions may be made where justified.  
For categorical data the following rules will be applied:  
● For ordered categorical data (eg, adverse event [AE] severity), all categories between 
the possible minimum and maximum categories will be included, even if n = 0 for a 
given category.  


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● For non-ordered categorical data (eg, race), only those categories for which there is at 
least 1 subject represented will be included; unless specifically stated otherwise.  
● Missing values will not be imputed, unless specifically stated otherwise. A ‘missing’ 
category will be included for any parameter for which information is missing. This 
will ensure that the population size totals are consistent across different parameters.  
8.1.3. Triplicate Readings  
For 12-lead electrocardiogram (ECG) data only, where triplicate readings are taken, the mean 
of triplicate readings will replace the separate individual triplicate readings in all calculations.  
In case of incomplete triplicate readings (eg, only 2 out of 3 readings were recorded), the 
mean and/or medians will be calculated, as appropriate, based on the number of readings 
available.  
8.1.4. Repeat and Unscheduled Readings  
For vital signs and 12-lead ECG data only, any predose value recorded in addition to the 
original value or a postdose value recorded within 15 minutes of the original value will be 
defined as a repeat value; any postdose value recorded more than 15 minutes after the 
original value will be defined as an unscheduled value. For all other data types (eg, laboratory 
parameters), any value recorded in addition to the original value will be defined as an 
unscheduled value.  
  
As unscheduled values are not associated with any scheduled timepoint, they will be 
excluded from all calculations unless specifically stated otherwise.  
8.1.5. Definitions of Baseline and Change from Baseline  
The baseline will be defined as the last value recorded prior to dosing. If the date/time of the 
value is incomplete or missing, it will be excluded from the baseline calculation, unless the 
incomplete date/time indicates the value was recorded prior to dosing.  
Individual changes from baseline will be calculated by subtracting the individual subject’s 
baseline value from the value at the postdose timepoint.  
The summary statistics for change from baseline will be derived from individual subjects’ 
values (eg, mean change from baseline will be the mean of the individual changes from 
baseline for all subjects, rather than difference between the mean value at the postdose 
timepoint and mean value at baseline).  
See Section 8.1.4 for more detail on handling repeat and unscheduled readings in the 
calculations. See Section 8.1.3 for more detail on handling of triplicate readings in the 
calculations.  


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8.2. Subject Disposition and Population Assignment  
Subject disposition and population assignment will be listed.  
A summary table by group treatment sequence will be provided, based on the safety 
population.   
Screen failure data summary table will be provided separately, based on the all subjects 
population.  
8.3. Screening Demographics and Baseline Characteristics  
The screening demographics and baseline characteristics including age, sex, race, ethnicity, 
height, body weight, and body mass index will be listed.  
A summary table by group treatment sequence will be provided, based on the safety 
population.  
8.4. Prior and Concomitant Medication  
Prior medication will be defined as medication that ends prior to dosing. Concomitant 
medication will be defined as medication that starts during or after dosing or starts but does 
not end prior to dosing.  
Prior and concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHODrug) Global, Format B3, Version March 2021 (or later if a new version is 
issued during the study; see the data management plan [DMP] for more details). Prior and 
concomitant medications will be listed.  
8.5. Pharmacokinetic Assessments  
8.5.1. Pharmacokinetic Analysis  
The following PK parameters will be determined where possible from the plasma 
concentrations of CBP-307 and moxifloxacin using noncompartmental methods in validated 
software program Phoenix WinNonlin (Certara, Version 8.1 or higher): 
Moxifloxacin (Days 1 and 16) 
Parameter 
Unitsa 
Definition 
Cmax 
ng/mL 
maximum observed concentration 
tmax 
h 
time of the maximum observed concentration 
AUC0-tlast 
h*ng/mL 
area under the concentration-time curve from time 0 to the time 
of the last quantifiable concentration (tlast)b 
AUC0-24 
h 
area under the concentration-time curve over the time interval 
from 0 to 24 hours post dose 
CBP-307 (Days 1, 6 and 15) 


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AUCinf 
h*ng/mL 
area under the concentration-time curve from time 0 extrapolated 
to infinityc (Day 15 only) 
AUC0-tlast 
h*ng/mL 
area under the concentration-time curve from time 0 to the time 
of the last quantifiable concentration (tlast)b 
%AUCextrap 
% 
percentage of area under the concentration-time curve due to 
extrapolation from the last quantifiable concentration to infinity 
(Day 15 only) 
AUC0-24 
h 
area under the concentration-time curve over the time interval 
from 0 to 24 hours post dose 
Cmax 
ng/mL 
maximum observed concentration 
tmax 
h 
time of the maximum observed concentration 
tlast 
h 
time of the last quantifiable concentration 
t1/2 
h 
apparent terminal elimination half-life (Day 15 only) 
CL/F 
L/h 
apparent total clearance (Day 15 only) 
Vz/F 
L 
apparent volume of distribution during the terminal phase (Day 
15 only) 
a Units are based on concentration units (provided by the bioanalytical lab or preferred units for presentation of PK 
parameters) and dose units used in the study. 
b The AUC will be calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for 
decreasing concentrations (linear up/log down rule).  
c Based on the last observed quantifiable concentration 
Additional PK parameters may be determined where appropriate. 
Pharmacokinetic analysis will be carried out where possible using actual dose administered 
(mg) and actual postdose blood sampling times. If an actual time is missing, the sample 
concentration result will be treated as missing unless there is scientific justification to include 
the result using the nominal time. 
The parameters Cmax, tlast, and tmax will be obtained directly from the concentration-time 
profiles. If Cmax occurs at more than 1 timepoint, tmax will be assigned to the first occurrence 
of Cmax. 
8.5.1.1. Criteria for the Calculation of Apparent Terminal Elimination Rate Constant 
and Half-life 
The start of the terminal elimination phase for each subject will be defined by visual 
inspection and generally will be the first point at which there is no systematic deviation from 
the log-linear decline in concentrations. 
The apparent terminal elimination rate constant (λz) will only be calculated when a reliable 
estimate can be obtained using at least 3 data points, preferably not including Cmax, and the 
adjusted coefficient for determination of exponential fit (R2-adj) of the regression line is ≥0.7. 
Parameters requiring λz for their calculation (eg, AUCinf, t1/2, CL/F, and Vz/F for Profile Day 
15) will only be calculated if the R2-adj value of the regression line is ≥0.7. 
The following regression-related diagnostic PK parameters will be determined, when 
possible: 


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Parameter 
Units 
Definition 
λz 
1/h 
apparent terminal elimination rate constant 
λz Upper 
h 
end of exponential fit 
λz Lower 
h 
start of exponential fit 
λz N 
NA 
number of data points included in the log-linear regression 
λz Span Ratio 
NA 
time period over which λz was determined as a ratio of t1/2 
R2-adj 
NA 
adjusted coefficient for determination of exponential fit 
Where possible, the span of time used in the determination of λz (ie, the difference between λz 
Upper and λz Lower) should be ≥2 half-lives. If the λz Span Ratio is <2, the robustness of the 
t1/2 values will be discussed in the clinical study report (CSR). 
8.5.1.2. Criteria for Calculation and Reporting of Area Under the Concentration-time 
Curve 
The minimum requirement for the calculation of AUC will be the inclusion of at least 
3 consecutive concentrations above the lower limit of quantification. If there are only 
3 consecutive concentrations, at least 1 should follow Cmax.  
If the extrapolated area is >20%, AUCinf (and derived parameters) may be excluded from the 
summary statistics at the discretion of the sponsor or pharmacokineticist.  
8.5.1.3. Criteria for Handling Concentration Below the Limit of Quantification or 
Missing Concentrations for Pharmacokinetic Analysis 
Plasma concentrations below the limit of quantification (BLQ) will be assigned a value of 0 
before the first measurable concentration and thereafter BLQ concentrations will be treated as 
missing. The following rules apply to the specific situations defined below: 
● If an entire concentration-time profile is BLQ, it will be excluded from PK analysis. 
● Where 2 or more consecutive concentrations are BLQ at the end of a profile, the 
profile will be deemed to have terminated and any further quantifiable concentrations 
will be set to missing for the calculation of the PK parameters, unless they are 
considered to be a true characteristic of the profile of the drug. 
● If a predose plasma concentration is missing, it will be set to 0 by default within 
Phoenix WinNonlin for the first dosing day (Study Profile Day 1). 
● For multiple dose part of the study (Study Profile Day 15), if the CBP-307 
concentration at 24 hours postdose is missing, this may be substituted with the 
predose. 


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8.5.1.4. Treatment of Outliers in Pharmacokinetic Analysis 
If a value is considered to be anomalous due to being inconsistent with the expected PK 
profile, it may be appropriate to exclude the value from the PK analysis. However, the 
exclusion of any data must have strong justification and will be documented in the CSR. 
Any quantifiable predose concentration value on the first dosing day (Study Profile Day 1) 
will be considered anomalous and set to missing for the PK analysis. This will be set to 0 by 
default in Phoenix WinNonlin. 
8.5.2. Presentation of Pharmacokinetic Data 
All PK concentrations and parameters will be listed.  
Summary tables, arithmetic mean (+ standard deviation [SD]) figures, overlaying individual 
figures, and individual figures by appropriate treatment and time postdose will be provided 
for plasma PK concentrations. All figures will be produced on both linear-linear and linear-
logarithmic scales, with the exception of figures across all days, which will be produced on 
the linear-linear scale only. The +SD bars will only be displayed on the linear-linear scale.  
Summary tables by appropriate treatment will be provided for all PK parameters, with the 
exception of diagnostic regression-related PK parameters.  
A subject may be excluded from the PK summary statistics and statistical analysis if the 
subject has an AE of vomiting that occurs at or before 2 times the median tmax.  Where 
subjects tested positive for COVID-19, data will only be listed where available. 
If the actual time of sample collection deviates from the allowed PK sample collection 
window, the plasma concentration will be flagged and excluded from the summary statistics.  
Individual concentrations deemed to be anomalous will be flagged in the listings and 
excluded from the summary statistics. 
For plasma concentration data the following rules will apply: 
● Values that are BLQ will be set to 0 for the calculation of summary statistics. 
● Arithmetic mean or median values that are BLQ will be presented as 0. 
For PK parameters the following rule will apply: 
Geometric mean and coefficient of variation will not be calculated for tlast and tmax  
8.5.3. Pharmacokinetic Statistical Methodology  
No inferential statistical analyses are planned.   


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8.6. Safety and Tolerability Assessments  
8.6.1. Adverse Events  
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 24.0 (or higher if a new version is issued during the study; see the DMP for more 
details).  
A treatment-emergent adverse event (TEAE) will be defined as an AE that starts during or 
after dosing on Day 1, or starts prior to dosing on Day 1 and increases in severity after each 
dosing.  
A treatment related TEAE will be defined as a TEAE with a relationship of possibly related 
or related to the study treatment, as determined by the investigator.   
All AEs will be listed. In addition to the data recorded in the database, the listings will 
include derived onset time and duration. Onset time will be calculated from the time of 
dosing for TEAEs only. Where the last associated dose is referring to the last dose received 
prior to the start of a TEAE.   
The frequency of subjects with TEAEs and the number of TEAEs will be summarized for the 
following categories:  
● TEAEs (overall, serious, leading to discontinuation, and leading to death) by 
treatment  
● TEAEs by severity and treatment  
● Treatment-related TEAEs (overall, serious, leading to discontinuation, and leading to 
death) by treatment  
● Treatment-related TEAEs by severity and treatment  
The frequency of subjects will be summarized separately for TEAEs and treatment-related 
TEAEs by the following:  
● System organ class, preferred term, and treatment  
● Preferred term and treatment  
For the AE data the following rules will apply:  
● For the derivation of treatment-emergent status (applicable to all AEs): The collecting 
time window for AEs will be from after the time of signing the ICF until end of study 
(EOS) 
● For the derivation of treatment-emergent status (applicable to all AEs): If the start 
date/time of an AE is incomplete or missing, an AE will be assumed to be a TEAE, 
unless the incomplete start date/time or the end date/time indicates an AE started 


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before dosing. For the derivation of treatment-related status (applicable to TEAEs 
only): If the study treatment relationship for a TEAE is missing, a TEAE will be 
assumed to be a treatment-related TEAE.  
● For the derivation of onset time (applicable to TEAEs only): If the start date/time of a 
TEAE is missing, onset time will not be calculated. If the start date/time of a TEAE is 
incomplete, where possible, the minimum possible onset time will be calculated and 
presented in ‘≥DD:HH:MM’ format (eg, if the date/time of dosing is 
01MAY2019/08:00 and recorded start date/time of a TEAE is 03MAY2019, then the 
minimum possible onset time will be calculated by assuming a TEAE started at the 
first hour and minute of 03MAY2019 [03MAY2019/00:00], thus will be presented as 
onset time ≥01:16:00 in the listing). If the start date of a TEAE is the same as the date 
of dosing but the start time of a TEAE is missing, an onset time will be presented as 
‘≥00:00:01’. Any clock changes will be accounted for in the derivation.  
● For the derivation of duration (applicable to all AEs): If the end date/time of an AE is 
missing, duration will not be calculated. If the start or end date/time of an AE is 
incomplete, where possible, the maximum possible duration will be calculated and 
presented in ‘≤DD:HH:MM’ format (eg, if the start of an AE date/time is 
01MAY2019/08:00 and its recorded end date/time is 03MAY2019, then the 
maximum possible duration will be calculated by assuming an AE ended at the last 
hour and minute of 03MAY2019 [03MAY2019/23:59], thus will be presented as 
duration ≤02:15:59 in the listing). Any clock changes will be accounted for in the 
derivation.  
● For the calculation of TEAE summary statistics: If the severity of a TEAE is missing, 
that TEAE will be counted under the ‘missing’ category. 
● For the calculation of TEAE summary statistics: Counting rules for TEAEs: The 
collecting time window for TEAEs will be from the time of dosing on Day 1 until 
study completion (Day 1~EOS). 
o For CBP-307 0.05mg dose, only count/collect/record TEAEs that starts or 
increases in severity during the dosing level of CBP-307 0.05mg (from the 
time of dosing 0.05mg on Day 1 until the start of dosing 0.1mg on Day 2), 
irrespective of the TEAE’s ending time. 
o For CBP-307 0.1mg dose, only count/collect/record TEAEs that starts or 
increases in severity during the dosing level of CBP-307 0.1mg (from the time 
of dosing 0.1mg on Day 2 until the start of dosing 0.2mg on Day 3), 
irrespective of the TEAE’s ending time. 
o For CBP-307 0.2mg dose, only count/collect/record TEAEs that starts or 
increases in severity during the dosing level of CBP-307 0.2mg (from the time 
of dosing 0.2mg on Day 3 until the start of dosing 0.5mg on Day 7), 
irrespective of the TEAE’s ending time. 


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o For CBP-307 0.5mg dose, only count/collect/record TEAEs that starts or 
increases in severity from the time of dosing 0.5mg on Day 7 until study 
completion (Day 7~EOS), irrespective of the TEAE’s ending time. 
● For the calculation of TEAE summary statistics: If a subject experienced multiple 
TEAEs with the same preferred term for the same treatment, this will be counted as 1 
TEAE for that treatment under the maximum severity recorded.  
8.6.2. Clinical Laboratory Parameters  
All clinical laboratory parameters, their changes from baseline will be listed, as applicable; 
any value outside the clinical reference range will be flagged. Separate listings will be 
provided for any parameter for which there is any individual subject value outside the 
respective clinical reference range.  
Summary tables by group treatment sequence and timepoint will be provided for clinical 
chemistry, hematology parameters, their changes from baseline as applicable.  
Where data available, shifts from baseline tables will be provided for clinical chemistry and 
hematology parameters. 
Values recorded as <x, ≤x, >x, or ≥x will be displayed in the listings as recorded. For the 
derivation of listing flags, all calculations, and presentation in the figures, <x and ≤x values 
will be set to 0, whereas >x and ≥x values will be set to x.  
8.6.3. Vital Signs Parameters  
All vital signs parameters, their changes from baseline will be listed, as applicable; any value 
outside the clinical reference range will be flagged.  
Summary tables by group treatment sequence and timepoint will be provided for all vital 
signs parameters, their changes from baseline, as applicable.  
Where data available, shifts from baseline tables will be provided for vital sign parameters. 
8.6.4. Safety 12-lead Electrocardiogram Parameters  
All 12-lead ECG parameters, their changes from baseline, will be listed; any value outside the 
clinical reference range will be flagged.  
Summary tables by group treatment sequence and timepoint will be provided for all 12-lead 
ECG parameters, their changes from baseline.  
Where data available, shifts from baseline tables will be provided for 12-lead ECG 
parameters. 
An outlier analysis will be performed for QT interval corrected for heart rate using Bazett’s 
formula (QTcB) and QT interval corrected for heart rate using Fridericia’s formula (QTcF). 
The analysis will include all individual original, repeat, and unscheduled postdose values.  


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The maximum postdose values will be summarized by treatment according to the following 
categories:  
● ≤450 ms  
● >450 and ≤480 ms (all instances flagged in the listing)  
● >480 and ≤500 ms (all instances flagged in the listing)  
● >500 ms (all instances flagged in the listing)  
The maximum increases from baseline will be summarized by treatment according to the 
following categories:  
● ≤30 ms  
● >30 and ≤60 ms (all instances flagged in the listing)  
>60 ms (all instances flagged in the listing) 
8.6.5. Cardiac Telemetry Monitoring 
All cardiac telemetry data will be listed.  
Where data available, shifts from baseline tables will be provided for cardiac telemetry 
monitoring data. 
8.6.6. Other Assessments  
Medical history will be listed.  
All other safety and tolerability assessments not detailed in the above sections such as 
physical examination and cardiac telemetry monitoring will be listed only.  
8.6.7. Safety and Tolerability Statistical Methodology  
No inferential statistical analysis is planned.  
9. INTERIM ANALYSES  
No interim analysis is planned.  
10. SIGNIFICANT CHANGES FROM THE PROTOCOL-SPECIFIED ANALYSES  
There were no significant changes from the protocol -specified analyses.  
11. REFERENCES  
1. ICH. ICH Harmonised Tripartite Guideline: Structure and content of clinical study reports 
(E3). 30 November 1995.  


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2. ICH. ICH Harmonised Tripartite Guideline: General considerations for clinical trials (E8). 
17 July 1997.  
3. ICH. ICH Harmonised Tripartite Guideline: Statistical principles for clinical trials (E9). 
5 February 1998.  
4. Darpo B, Benson C, Dota C, et al. Results from the IQ-CSRC prospective study support 
replacement of the thorough QT study by QT assessment in the early clinical phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
5. Ferber G, M Zhou, B Darpo. Detection of QTc effects in small studies--implications for 
replacing the thorough QT study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
6. Huang DP, Chen J, Dang Q, et al. Assay sensitivity in “Hybrid thorough QT/QTc (TQT)” 
study. Journal of Biopharmaceutical Statistics. 2019;29(2):378-384. 


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ST-AD-031 Version 02 
12. APPENDICES 
Appendix 1: 
Document History 
Status and Version 
Date of Change Summary/Reason for Changes 
Final Version 1.0 
NA 
NA; the first version. 
NA = not applicable 
 


Statistical Analysis Plan (SAP)/Initiation of 
Programming Approval Form
COVANCE INC. CONFIDENTIAL
Page 1 of 1
ST-AD-030 version 01
Type of Approval (select one) :   
SAP    
Initiation of Programming
Sponsor
Name:
Suzhou Connect Biopharmaceuticals
Sponsor
Protocol/
CIP ID:
CBP-307AU002
Covance 
Study ID:
000000216292
SAP text 
filename:
CBP-
307AU002_SAP_V2_Final_10May2
022.pdf
TFL shells 
filename:
CBP-
307AU002_TFL_V2_Final_10May2
022.pdf
Version:
2.0
Date:
10May2022
Covance Approval(s):
Lead Statistician
Approval Signature
Print Name
Job Title
Date
Sponsor Approval(s):
By signing below when the statistical analysis plan (SAP) is considered final, the 
signatories agree to the analyses to be performed for this study and to the format of 
the associated tables, figures, and listings (TFLs). Once the SAP has been signed, 
programming of the Analysis Dataset Model (ADaM) datasets and TFLs based on these
documents can proceed. Any modifications to the SAP text and TFL shells made after 
signing may result in a work-scope change.
Approval Signature
Print Name
Job Title
Date
Please scan/email completed form(s) to the Lead Statistician listed below:
Printed Name/Title:
Wei Xiao, Biostatistician
Email:
Wei.xiao@covance.com
Clinical Project Manager
16 May 2022

□ 
W'eiXiao 
Wei Xiao 
Biostatistician 
I approved this document 
16 May 2022 8:19 AM -05:00 
(
DocuSigned by: 
I Jt,ssit,.CL.,u., 
l(J 
Signer Name: Jessie Chen 
L
Signing Reason: I have reviewed this document 
Signing Time: 2022/5/15 I 7:21 :46 PM PDT 
2F87 403915664 7FCBB57186A 19DC391 A 


Statistical Analysis Plan for Suzhou Connect Biopharmaceuticals, Ltd., Study CBP-307AU002 
Page 1 of 26 
Version 1.0 
 
CONFIDENTIAL 
 
 
 
 
Cardiac Statistical Analysis Plan 
 
 
A Phase I, Multicenter, Randomized, Double-blind, 
Double-dummy, Placebo- and Positive-Controlled 
Study to Investigate the Effects of CBP-307 on the QTC 
Interval in Healthy Subjects 
 
 
 
 
Protocol: CBP-307AU002 
 
 
Prepared For: 
Suzhou Connect Biopharmaceuticals, Ltd. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Version:  
1.0 
Authors:  
 Xingchi Wang, MS, Biostatistician I 
 
 
Hongqi Xue, PhD, Sr. Principal Biostatistician 
Date:   
11 March 2022 


 
 
Statistical Analysis Plan for Suzhou Connect Biopharmaceuticals, Ltd., Study CBP-307AU002 
Page 2 of 26 
Version 1.0 
 
CONFIDENTIAL 
Revision History 
Version 
Issue Date 
Author(s) 
Description 
Draft 0.1 
14 Dec 2021 
Xingchi Wang and 
Hongqi Xue 
Initial version for review.  
Draft 0.2 
10 January 2022 
Hongqi Xue 
Revised version per comments.  
Draft 0.3 
24 January 2022 
Hongqi Xue 
Updated per protocol.  
1.0 
1 March 2022 
Hongqi Xue 
Final version. 
 
 
 
 
 


 
 
Statistical Analysis Plan for Suzhou Connect Biopharmaceuticals, Ltd., Study CBP-307AU002 
Page 3 of 26 
Version 1.0 
 
CONFIDENTIAL 
Table of Contents 
1 Abbreviations .............................................................................................................................4 
2 Introduction ................................................................................................................................5 
3 Study Design ..............................................................................................................................5 
4 Cardiodynamic ECG Assessment ..............................................................................................6 
4.1 
ECG and Pharmacokinetic Sample Collection ...................................................................6 
4.2 
Cardiodynamic ECG Objectives .........................................................................................6 
4.3 
Cardiodynamic ECG Endpoints .........................................................................................7 
5 Statistical Methods .....................................................................................................................7 
5.1 
General Methodology .........................................................................................................7 
5.2 
Analysis Populations (Subject-Level) and Record-Level Analysis Sets ............................7 
5.3 
Baseline ...............................................................................................................................9 
5.4 
QT Correction Methods ....................................................................................................10 
5.5   Terminology and Definitions: Placebo-corrected ΔQTcF and Placebo-adjusted ΔQTcF 
(ΔΔQTcF) ..................................................................................................................................10 
6 Analysis....................................................................................................................................11 
6.1 
Concentration-QTc Analysis (Primary Analysis) .............................................................11 
6.1.1 Investigation of Hysteresis .........................................................................................13 
6.1.2 Appropriateness of a Linear Model ............................................................................13 
6.2 
Assay Sensitivity ..............................................................................................................13 
6.3 
By-Time Point Analysis ...................................................................................................14 
6.4 
Categorical Analysis .........................................................................................................15 
6.5 
Morphological analysis for T-wave and U-wave .............................................................16 
6.6 
Determination of Sample Size ..........................................................................................17 
7 References ................................................................................................................................18 
8 Tables, Figures, and Listings ...................................................................................................18 
8.1 
Tables ................................................................................................................................18 
8.2 
Figures ..............................................................................................................................20 
8.3 
Listings .............................................................................................................................24 
9 Approvals .................................................................................................................................25 
Appendix A: Early Precision QT Analysis ....................................................................................26 
 
 
 


 
 
Statistical Analysis Plan for Suzhou Connect Biopharmaceuticals, Ltd., Study CBP-307AU002 
Page 4 of 26 
Version 1.0 
 
CONFIDENTIAL 
1 Abbreviations 
Abbreviation 
Term/Description 
bpm 
Beats per minute 
CI 
Confidence interval 
C-QTc 
Concentration-QTc 
Cmax 
Maximum plasma concentration 
 
Change-from-baseline 
ΔΔ 
Placebo-corrected or placebo-adjusted change-from-baseline 
ECG 
Electrocardiogram 
HR 
Heart rate 
LOESS 
Locally weighted scatter plot smoothing 
LS 
Least squares 
ms 
Millisecond 
PK 
Pharmacokinetic(s) 
PR 
PR interval of the ECG 
Q-Q 
Quantile-quantile 
QRS 
QRS interval of the ECG 
QT 
QT interval of the ECG 
QTc 
Corrected QT interval 
QTcF 
Corrected QT interval using Fridericia’s formula 
RR 
RR interval of the ECG 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
Tmax 
Time of peak plasma concentration 
TQT 
Thorough QT 
 
 


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2 Introduction 
This statistical analysis plan (SAP) was developed after review of protocol CBP-307AU002 
(Version 5.0 dated 12 January 2022) for the study “A Phase I, Multicenter, Randomized, Double-
blind, Double-dummy, Placebo- and Positive-Controlled Study to Investigate the Effects of 
CBP-307 on the QTC Interval in Healthy Subjects” and the ERT contract/proposal. This 
document defines the populations to be analyzed and provides full details of the statistical 
analyses, data displays, and algorithms to be used for data derivations to aid in the production of 
the statistical output and the statistical section of the cardiac safety report in regard to 
electrocardiogram (ECG) and concentration-QTc analyses. Relevant subject characteristics as 
well as the electrocardiographic parameters that will be evaluated are described along with the 
specific statistical methods.  
3 Study Design 
This will be a Phase I, randomized, double-blind, double-dummy, placebo-controlled, positive-
controlled, multi-site, 3-arm study to investigate the effects of therapeutic and supratherapeutic 
oral doses of CBP-307 on the QTc interval in healthy male and female  subjects.  
In this study, approximately 68 healthy subjects (at least 30% for each sex) will be randomized 
into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-groups (Group 
2A and 2B) and each sub-group will be randomized with 17 subjects. Randomized subjects will 
receive the assigned study drug as a single dose in the morning under fasting conditions on Days 
1, 2, 3 to 6, 7, to 15, and on Day 16 (placebo will be administered to all subjects on Day -1). 
The following treatments will be administered: 

Starting doses of CBP-307 for titration (0.05 mg on Day 1 followed by an up-titrated
dose of 0.1 mg on Day 2)

A therapeutic dose of CBP-307 (0.2 mg, Days 3 to 6)

A supratherapeutic dose of CBP-307 (0.5 mg, Days 7 to 15)

Placebo (matched to moxifloxacin and CBP-307)

Moxifloxacin (400 mg)
Moxifloxacin will be used as a positive control to determine the assay sensitivity of this study 
with an expected peak QT effect (placebo-corrected change-from-baseline QTcF; ∆∆QTcF) of
10 to 15 ms. 
Potential subjects will be screened to assess their eligibility to enter the study within 27 days 
prior to the first dose administration. Subjects will be admitted into the study site on Day -2 (or 
on Day -4 depending on the clinical site’s requirement for Coronavirus Disease 2019 [COVID-
19] testing) and will remain at the study site until discharge on Day 19.


 
 
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4 Cardiodynamic ECG Assessment 
4.1 ECG and Pharmacokinetic Sample Collection 
Continuous Holter ECG recordings will be performed before dosing for 25 hours on 
Days -1, 1, 6, 15, and 16 and continue through 12 or 24 hours post-dose. Replicate 12-lead 
ECGs will be extracted from the continuous recording prior to dosing (-30 minutes) and 0.5, 
1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on each day. At each time point, up to 10 ECG 
replicates will be extracted from a 5-minute time window (the last 5 minutes of the 15-
minute period when the subject is maintained in a supine, quiet position). The ECG effects 
of CBP-307 will be tested on data from Day -1 (baseline for both groups), Day 6 
(therapeutic concentrations versus placebo), and Day 15 (supratherapeutic concentrations 
versus placebo). Assay sensitivity with moxifloxacin will be evaluated using ECG data 
collected on Days -1, 1, 15, and 16. 
Pharmacokinetic blood samples will be collected at the following time points: prior to 
dosing and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after dosing on each PK sampling day 
(Days 1, 6, 15, and 16; sample collection windows are as follows: ±2 minutes for 0.5 hours 
post-dose, ±5 minutes for 1 to 4 hours post-dose, ±10 minutes for 6 to 8 hours post-dose, 
and ±30 minutes for 12 to 24 hours post-dose). Additional PK samples will be collected at 
72 and 96 hours following dosing on Day 15 (sample collection window: ±30 minutes). 
All Holter/ECG data will be collected using M12R continuous 12-lead digital recorders and 
the M12A Enterprise Holter System Client (Global Instrumentation, LLC, Manlius, NY, 
USA). The equipment will be supplied and supported by ERT. 
ECG intervals will be measured by the core laboratory in a blinded manner using the Early 
Precision QT technique (EPQT) (see Appendix A for more details). The ECG database will be 
locked before any statistical analysis is undertaken. 
4.2 Cardiodynamic ECG Objectives 
For the purpose of this analysis plan, objectives related to ECG assessment are described. 
The primary ECG objective of the study is to evaluate the effect of therapeutic and 
supratherapeutic CBP-307 plasma concentrations on the heart-rate corrected QT interval (QTc) 
in healthy subjects. 
The secondary ECG objectives of the study are:  
 To demonstrate assay sensitivity of the study to detect a small QT effect using 
moxifloxacin as a positive control. 
 To evaluate the effects of therapeutic and supratherapeutic multiple oral doses of CBP-
307 on HR, PR and QRS intervals, and T-wave morphology. 


 
 
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4.3 Cardiodynamic ECG Endpoints 
The primary ECG endpoint of this study is the change-from-baseline QTcF (ΔQTcF).  
The secondary endpoints are:  
 Change-from-baseline HR and PR and QRS intervals (∆HR, ∆PR, and ∆QRS); 
 Placebo-corrected change-from-baseline HR, QTcF, PR, and QRS (HR, QTcF, 
PR, and QRS); 
 Categorical outliers for QTcF, HR, PR, and QRS; 
 Frequency of treatment-emergent changes for T-wave morphology and U-wave presence  
5 Statistical Methods 
5.1 General Methodology 
All statistical analyses will be performed using the statistical software SAS for Windows 
Version 9.4 or higher (SAS Institute, Inc., Cary, NC). Data collected from all subjects enrolled in 
the study who receive at least 1 dose of study treatment (CBP-307, moxifloxacin, or placebo) 
will be presented in data listings. Both observed values and change-from-baseline values for each 
subject will be given where applicable. All continuous data will be listed with the same precision 
as will be presented in the database. Data listings will be sorted by subject ID, treatment, visit (or 
day), and time point. Missing values will be represented by an empty cell and no imputation will 
be made. 
For all descriptive statistics of continuous ECG parameters (i.e., HR, PR, QRS, and QTc), data 
will be summarized including number of subjects (n), mean, median, standard deviation (SD), 
90% confidence interval (CI), minimum, and maximum by treatment and time point. For all 
modeling results of the by-time-point analysis of change-from-baseline values of continuous 
ECG parameters, n, least squares (LS) mean, standard error (SE), and 90% CI will be included. 
Modeling results of the by-time point analysis of placebo-corrected change-from-baseline will 
also include LS mean, SE, and 90% CI. Mean and median values will be rounded to the nearest 
tenth. SD, SE, and CI will be rounded to the nearest hundredth. For the concentration-QTc 
analysis, 2 decimal places will be shown for all effect estimates for all results which have an 
absolute value greater than 0.05. Each effect estimate with an absolute value ≤ 0.05 will be 
displayed with 2 significant figures. The CI of the effect estimate will display 1 more decimal 
place than the effect estimate. SE and P values will be reported with 4 digits and 
P values < 0.0001 will be reported as < 0.0001. Degrees of freedom (df) and t-value will be 
reported to the nearest tenth and nearest hundredth, respectively. Percentages will be rounded to 
the nearest tenths decimal place. 
5.2 Analysis Populations (Subject-Level) and Record-Level Analysis Sets 
The analysis populations (subject-level) for cardiodynamic ECG assessment are defined as 
follows (Table 1).  


 
 
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Table 1 
Analysis populations (subject-level) for cardiodynamic ECG assessment 
Analysis 
Population 
Definition 
PK population 
All subjects who received at least 1 dose of study treatment 
(therapeutic and supratherapeutic doses of CBP-307, moxifloxacin) 
and have evaluable PK data of any of the analytes  (CBP-307 and 
moxifloxacin). A subject will be excluded from the PK summary 
statistics and statistical analysis if the subject has an adverse event of 
vomiting that occurs at or before 2 times median time to maximum 
concentration. 
QT/QTc population 
All subjects who received at least 1 dose of study treatment 
(therapeutic and supratherapeutic doses of CBP-307, moxifloxacin, or 
placebo) with measurements at baseline as well as on-treatment with at 
least 1 post-dose time point with a valid ΔQTcF value. The QT/QTc set 
will be used for the by-time point, categorical, and morphological 
analyses of cardiodynamic ECG parameters. 
PK/QTc population 
All subjects who are in both the PK and QT/QTc populations with at 
least 1 pair of post-dose PK and ΔQTcF data from the same time point 
as well as subjects in the QT/QTc population who received placebo. 
The PK/QTc Set will be used for the concentration-QTc (C-QTc) 
analysis and assay sensitivity. PK/QTc Set will be defined for CBP-307 
and for moxifloxacin. 
Table 2 defines the observations that will be included at a record/time point level in the statistical 
analyses described in this SAP. 
Table 2 
Record-level analysis sets for cardiodynamic ECG assessment 
Analysis set 
Definition 
By-time point 
analysis set 
Each post-baseline time point that has a nonmissing change-from-
baseline observation. Defined for all continuous ECG parameters for 
subjects in the QT/QTc population. 
Categorical 
analysis set 
For continouous ECG parameters, each post-baseline time point that has 
a nonmissing change-from-baseline observation. For all categorical 
ECG parameters, each evaluable post-baseline time point that has an 
evaluable record at baseline, i.e., treatment-emergent changes can be 
assessed. Defined for all subjects in the QT/QTc population. 
Concentration-QTc 
analysis set 
All time points in the by-time point population that have a 
corresponding planned PK collection at the same time point as well as 
time points in the by-time point analysis with subjects receiving 
placebo. Time points at which no PK data are available for nonplacebo 
subjects will not be retained. Defined for QTc for subjects in the 
PK/QTc population. 


 
 
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5.3 Baseline 
Baseline for the assessment of the ECG effect of CBP-307 (CBP-307 in Group 1 versus placebo 
in Groups 2A and 2B) will be time-matched values on Day -1 (Table 3). 
For assay sensitivity in Groups 2A and 2B, the following baselines will be used: 
 Group 2A: For moxifloxacin administered on Day 1 (defined as Period 1 Day 1), baseline 
will be Day 16 (defined as Period 1 Day -1), on which subjects are administered placebo. 
For placebo-correction in this group, placebo values will be derived from Day 15 
(defined as Period 2 Day 1) on which subjects are administered placebo, and baseline will 
be obtained on Day -1 (defined as Period 2 Day -1). 
 Group 2B: For moxifloxacin administered on Day 16 (defined as Period 2 Day 1), 
baseline will be Day 1 (defined as Period 2 Day -1), on which subjects are administered 
placebo. For the placebo-correction in this group, Day -1 (defined as Period 1 Day 1) 
values will be used as placebo (no treatment) and baseline will be obtained on Day 15 
(defined as Period 1 Day -1). 
For T-wave morphology and U-wave presence, baseline includes findings observed in any 
replicates from all time points that constitute baseline. 
Table 3 
Treatment administration and baseline definition 
Day 
Treatment Arm 
Control Arm 
Group 1 
Group 2A 
Group 2B 
-1 
CBP-307 placebo 
Baseline for T1, T2, T3   
CBP-307 placebo 
Baseline for T5 and T6; 
Baseline for T8 moxifloxacin-
placebo on Day 15 
CBP-307 placebo 
Baseline for T4, T5 and T6; 
T8: moxifloxacin-placebo on 
Day -1; 
1  
CBP-307 0.05 mg 
Moxifloxacin-placebo 
T1: CBP-307 0.05 mg 
on Day 1  
400 mg Moxifloxacin 
CBP-placebo   
T7: moxifloxacin on Day 1 
Moxifloxacin-placebo 
CBP-placebo 
T4: corresponding placebo on 
Day 1;  
Baseline for T7 on Day 16 
6 
CBP-307 0.2 mg 
T2: CBP-307 0.2 mg 
on Day 6 
CBP-307-placebo 
T5: corresponding placebo on 
Day 6 
CBP-307-placebo 
T5: corresponding placebo on 
Day 6 
15 
CBP-307 0.5 mg 
T3: CBP-307 0.5 mg 
on Day 15 
CBP-307-placebo 
T6: corresponding placebo on 
Day 15 
T8: moxifloxacin-placebo on 
Day 15 
CBP-307-placebo 
T6: corresponding placebo on 
Day 15; 
Baseline for T8 moxifloxacin-
placebo on Day -1 
16  
CBP-307 placebo 
Moxifloxacin-placebo 
(not analyzed) 
 
CBP-307 placebo 
Moxifloxacin-placebo 
Baseline for T7 on Day 1 
CBP-307 placebo 
400 mg Moxifloxacin 
T7: moxifloxacin on Day 16 
 
Note: To facilitate analysis, the nested crossover design for the moxifloxacin/placebo 
comparison for assay sensitivity needs to be coded following a 2-period crossover study design 


 
 
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with time-matched baseline on Day -1 in each period. The observations from Groups 2A and 2B 
will be relabeled (see Table 4). For example, for Group 2A, the moxifloxacin-placebo arm, 
baseline is Day 16 for the moxifloxacin day (Day 1) and baseline is Day -1 for the placebo day 
(Day 15). Therefore, Day 1 and Day 15 will be coded as Day 1, and Day -1 and Day 16 will be 
coded as Day -1.  
Table 4 
Period definition for Group 2A and 2B 
Treatment Days (per Table 3) 
Sub-group Treatment 
Period 
-1 
1 
15 
16 
2A 
Moxi/Placebo Period 1 (Moxi) 
Day 1 
Day -1 
Period 2 (Placebo) 
Day -1 
Day 1 
2B 
Placebo/Moxi Period 1 (Placebo) 
Day 1 
Day -1 
Period 2 (Moxi) 
Day -1 
Day 1 
5.4 QT Correction Methods 
The QT and RR value for each beat will be used for HR correction.  
The Fridericia's correction (QTcF) is defined as QTcF (ms) = QT (ms)/[RR(ms)/1000]1/3. 
For evaluation of the HR-corrected QT interval, a scatter plot and decile plot of QTc and RR 
intervals by treatment with a regression line and a linear mixed-effects line (90% CI), 
respectively, will also be given. 
5.5   Terminology and Definitions: Placebo-corrected ΔQTcF and Placebo-
adjusted ΔQTcF (ΔΔQTcF) 
Change-from-baseline QTcF (QTcF) will be used as the dependent variable in the 
concentration-QTc analysis and in the by-time point analysis.  
By-time point analysis 
Placebo-corrected ΔQTcF (ΔΔQTcF) 
 In the by-time point analysis on the QTcF interval, LS mean, SE, and 2-sided 90% CI of 
QTcF will be calculated for CBP-307 on Day 1, 6, and 15, for moxifloxacin and for 
placebo for CBP-307, and placebo for moxifloxacin at each post-dose time point. LS 
mean, SE, and 2-sided 90% CI of QTcF will be calculated for each CBP-307 dose 
group and for moxifloxacin group at each post-dose time point. 
Concentration-QTc analysis 
Placebo-corrected ΔQTcF (ΔΔQTcF) 
 In the concentration-QTc analysis, the term placebo-corrected ΔQTcF (ΔΔQTcF) will be 
used for the model-predicted effect across concentrations on a population level. 


 
 
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 Definition: Model-predicted mean ΔQTcF in each CBP-307 dose group (or moxifloxacin 
group) minus model-predicted mean ΔQTcF in the respective placebo group, which 
equals slope estimate × concentration + treatment effect-specific intercept.  
o The term placebo-corrected ΔQTcF (QTcF) will be used for the model-
predicted effect on the QTcF interval in the concentration-QTc prediction table 
and the scatter plots for concentration-QTc model(s), decile plots, and prediction 
plots, as described in Section 8. 
Placebo-adjusted ΔQTcF (ΔΔQTcF) 
 In the concentration-QTc analysis, the term placebo-adjusted ΔQTcF (ΔΔQTcF) will be 
used to illustrate the underlying data on both subject and population levels. 
 Definition for the estimated placebo-adjusted ΔQTcF on a subject level: observed ΔQTcF 
for each subject (on each CBP-307 dose group or moxifloxacin group or placebo group) 
minus the estimated time effect (i.e., the model-predicted mean ΔQTcF in the placebo 
group).  
o This term will be used to illustrate the underlying data on a subject level in the 
scatter plot(s) for concentration-QTc model(s), as described in Section 8.  
 Definition for the estimated placebo-adjusted ΔQTcF term on a population level: the 
average of individually estimated placebo-adjusted ΔQTcF values at the associated 
median plasma concentration within each concentration decile.  
o This term will be used to illustrate the underlying data on a population level in the 
decile plot(s), as described in Section 8.  
6 Analysis 
6.1 Concentration-QTc Analysis (Primary Analysis) 
The relationship between CBP-307 plasma concentrations and change-from-baseline QTcF 
(∆QTcF) will be quantified using a linear mixed-effects modeling approach with ΔQTcF as 
the dependent variable, time-matched concentrations of CBP-307 as the exploratory variate 
(0 for placebo), treatment (active=1 or placebo=0), and time (i.e., post-baseline time points 
on Days 1, 6, and 15: categorical) as fixed effects, and a random intercept and slope for 
concentrations per subject (Garnett et al1). Centered baseline QTcF (i.e., baseline QTcF for 
individual subject minus the population mean baseline QTcF for all subjects) will be 
included in this model as an additional covariate. If necessary, a sensitivity analysis will be 
performed using the model without this term. CBP-307 plasma concentrations below the 
quantifiable limit at pre-dose will be set to zero and after dosing will be set to 1/2 the lower 
limit of quantitation in the concentration-QTc analysis.   
An unstructured covariance matrix will be specified for the random effects. If convergence 
cannot be achieved even after appropriate rescaling of the concentrations, the random effect on 
the slope and intercept will be dropped, in this order, until convergence is achieved. The degrees 
of freedom of estimates will be determined by the Kenward-Roger method. From the model, the 
slope (i.e., the regression parameter for concentration) and the treatment effect-specific intercept 


 
 
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(defined as the difference between CBP-307 and placebo) will be estimated together with the 2-
sided 90% CI. The estimates for the time effect will be reported with degrees of freedom and SE. 
For the assessment of the ECG effect of CBP-307 versus placebo, the time term incorporated 
into the models (both by-time point analysis and concentration-QTc analysis [or assay 
sensitivity]) includes the single pre-dose time point and all post-dose time points on Days 1, 6, 
and 15, and Days 1 and 16 for active versus placebo and moxifloxacin versus placebo, 
respectively. All times are relative to the time of dosing on that day which is considered the first 
dose for the assay sensitivity analysis. For the analysis of CBP-307 versus placebo, the first dose 
of study treatment is on Day 1. 
The geometric mean of the individual Cmax values for subjects in CBP-307 group on each day of 
Days 1, 6, and 15 will be determined, respectively. The population point estimate and its 2-sided 
90% CI for the ΔΔQTcF (i.e., slope estimate × concentration + treatment effect-specific 
intercept) interval at these geometric mean Cmax will be obtained. If the upper bound of the 2-
sided 90% CI of the predicted ΔΔQTcF effect at the observed geometric mean Cmax of CBP-307 
on Days 6 and 15 is below 10 ms, it will be concluded that CBP-307 does not cause clinically 
relevant QTc prolongation within the observed plasma concentration ranges. 
To evaluate the adequacy of model fit with respect to the assumption of linearity, the observed 
ΔQTcF values adjusted by population time effect estimated from the model will be used. These 
individual placebo-adjusted ΔQTcFi,k (ΔΔQTcFi,k) values are derived as the observed individual 
ΔQTcFi,k for subject i administered with CBP-307 or placebo at time point k minus the estimated 
population mean placebo effect at time point k (i.e., time effect). A decile plot of observed drug 
concentrations and the mean placebo-adjusted ΔQTcF (ΔΔQTcF) and 90% CI at the median 
concentration within each decile will be given. The regression line presenting the model-
predicted ΔΔQTcF (as described by Tornøe et al2) will be added to evaluate the fit of a linear 
model and visualize the concentration-response relationship. Additional exploratory analyses 
(via graphical displays and/or model fitting) will include assessing for a delayed effect 
(hysteresis, Section 6.1.1) and the justification for the choice of the pharmacodynamic model 
(linear versus nonlinear, Section 6.1.2) as follows. 
The SAS code for the concentration-QTc analysis is as follows. 
PROC MIXED DATA=PKPD method=reml; 
CLASS SUBJID TIME; 
MODEL DQTc=TRT CONC TIME CBASE / solution cl noint alpha=0.1 alphap=0.1 COVB DDFM=KR;  
RANDOM INT CONC /TYPE=UN SUBJECT=SUBJID s; 
ESTIMATE 'Pred Mean Diff for T1' TRT 1 CONC &GeoMeanCmax_1 / CL ALPHA=0.1; 
RUN; 
 
Where PKPD = PK/QTc population, SUBJID = subject ID, TRT = treatment (1 for CBP-307, and 0 for placebo = 0), 
TIME = nominal post-baseline time point, CONC= plasma concentration of CBP-307, CBASE = centered baseline 
QTcF, T1= active dose on Day 1, GeoMeanCmax_1=geometric mean Cmax for T1, DQTc = ΔQTcF.  
Note: ESTIMATE statements will be repeated for active dose groups on Days 6, and 15. 


 
 
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6.1.1 Investigation of Hysteresis 
Hysteresis will be assessed based on joint graphical displays of the least squares (LS) mean 
ΔΔQTcF at each post-baseline time point from the by-time point analysis and the mean 
concentrations of CBP-307 at the same time points. In addition, hysteresis loops will be given for 
LS mean ΔΔQTcF from the by-time point analysis and the mean concentrations. Other 
concentration-QTc models such as a model with an effect compartment may be explored if all of 
the following 3 conditions are met. 
 A QT effect ≥ 10 ms (i.e., LS mean ΔΔQTcF  ≥ 10 ms) cannot be excluded in the by-time 
point analysis in the CBP-307 dose groups on Days 6 and 15 
 The mean peak ΔΔQTcF effect is observed at the same post-dose time point in the by-
time point analysis in the CBP-307 dose groups on Days 6 and 15 
 The difference (delay) between the time to reach the peak QTc effect (ΔΔQTcF) and Tmax 
is larger than 1 hour in a consistent way in the CBP-307 dose groups on Days 6 and 15 
With the provision stated above, hysteresis will be demonstrated if the curve of the hysteresis 
plot shows a counterclockwise loop. A significant treatment effect-specific intercept may also be 
indicative of hysteresis or model misspecification, if it cannot be explained by a nonlinear 
relationship. 
6.1.2 Appropriateness of a Linear Model 
To assess the appropriateness of a linear model, normal quantile-quantile (Q-Q) plots for the 
standardized residuals and the random effects will be produced. Scatter plots of standardized 
residuals versus concentration, versus model fitted values of ΔQTcF, and versus centered 
baseline QTcF (if available) will also be produced, as well as box plots of standardized residuals 
versus nominal time, and versus CBP-307 treatment. Among these plots, the scatter plots of 
standardized residuals versus concentration, and versus centered baseline QTcF (if available) 
will include the locally weighted scatter plot smoothing (LOESS, Cleveland3) line with an 
optimal smoothing parameter selected by the Akaike information criterion with a correction 
(AICC).(Hurvich et al4). A scatter plot of observed concentration and ΔQTcF with a LOESS 
smooth line with 90% CI and a linear regression line will also be provided to check the 
assumption of a linear concentration-QTc relationship. If there is an indication that a linear 
model is inappropriate, additional models may be fitted, specifically an Emax model. The 
concentration-QTc analysis will then be repeated for the model found to best accommodate the 
nonlinearity detected. 
6.2 Assay Sensitivity 
The analysis to show assay sensitivity will be based on the concentration-QTc analysis of the 
effect on Δ∆QTcF of 400 mg oral moxifloxacin using a similar model as for the primary 
analysis. That is, the relationship between moxifloxacin plasma concentration and ∆QTcF will be 
investigated by linear mixed-effects modeling. The model will include ΔQTcF as the dependent 
variable, moxifloxacin plasma concentration as the explanatory variable (0 for placebo), study 
treatment (1 for moxifloxacin and 0 for placebo) and time (i.e., post-baseline time point on Day 1 


 
 
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as defined in Table 4 for each period) as fixed effects, and random effects on intercept and slope 
per subject (Garnett et al1). Centered baseline QTcF will be included in this model as an 
additional covariate. If necessary, a sensitivity analysis will be performed using the model 
without this term. The geometric mean of the individual Cmax values for subjects receiving the 
single dose of 400 mg moxifloxacin will be determined. The predicted effect and its 2-sided 90% 
CI for ΔΔQTcF (i.e., slope estimate × concentration + treatment effect-specific intercept) at this 
geometric mean Cmax will be obtained.  
If the slope of the moxifloxacin plasma concentration/∆QTcF relationship is statistically 
significant at the 10% level in a 2-sided test and the lower bound of the 2-sided 90% CI of the 
predicted QT effect at the observed geometric Cmax of the 400 mg dose is above 5 ms, assay 
sensitivity will be deemed to have been demonstrated. 
The SAS code for the concentration-QTc analysis is as follows. 
PROC MIXED DATA=PKPD method=reml; 
CLASS SUBJID TIME; 
MODEL DQTc=TRT CONC TIME CBASE / solution cl noint alpha=0.1 alphap=0.1 COVB DDFM=KR;  
RANDOM INT CONC /TYPE=UN SUBJECT=SUBJID s; 
ESTIMATE 'Pred Mean Diff for T7' TRT 1 CONC &GeoMeanCmax_1 / CL ALPHA=0.1; 
RUN; 
 
Where PKPD = PK/QTc population, SUBJID = subject number, TRT = treatment (1 for moxifloxacin = 1 and 0 for 
placebo), TIME = nominal post-baseline time point on Day 1, CONC= plasma concentration of moxifloxacin, 
CBASE = centered baseline QTcF, T7= moxifloxacin group, GeoMeanCmax_1=geometric mean Cmax for T7, 
DQTc = ΔQTcF.  
6.3 By-Time Point Analysis  
The by-time point analysis for QTcF will be performed for CBP-307 versus placebo. A linear 
mixed-effects model will be used with ΔQTcF as the dependent variable and time (i.e., post-
baseline time point on Days 1, 6, and 15: categorical), treatment (therapeutic dose of CBP-307 
on Day 1, therapeutic dose of CBP-307 on Day 6, supratherapeutic dose of CBP-307 on Day 15, 
and corresponding placebo), and time-by-treatment interaction as fixed effects. Baseline QTcF 
will be included in this model as an additional covariate. If necessary, a sensitivity analysis will 
be performed using the model without this term. An unstructured covariance matrix will be 
specified for the repeated measures at post-baseline time points within subjects. If the model 
with an unstructured covariance matrix fails to converge, this by-time point analysis will be 
performed by day separately, and other covariance matrices such as compound symmetry and 
autoregressive will be considered, in this order, until convergence is achieved. From this 
analysis, the LS mean, SE, and 2-sided 90% CIs will be calculated for the contrast “CBP-307 
versus placebo” at each post-baseline time point on Days 1, 6, and Day 15, respectively. 
The by-time point analysis for QTcF will be also performed for moxifloxacin versus placebo at 
post-baseline time points on Day 1 (as defined in Table 4 for each period). A linear mixed-
effects model will be used with ΔQTcF as the dependent variable and time (i.e., post-baseline 
time points on Day 1: categorical), treatment (moxifloxacin and placebo), period (as defined in 
Section 5.3 and illustrated in Table 4), sequence (placebo/moxifloxacin or 
moxifloxacin/placebo), and time-by-treatment interaction as fixed effects. Baseline QTcF will be 


 
 
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included in this model as an additional covariate. If necessary, a sensitivity analysis will be 
performed using the model without this term. An unstructured covariance matrix will be 
specified for the repeated measures at post-baseline time points for subject within period. The 
model will also include a subject-specific random effect. If the model with an unstructured 
covariance matrix fails to converge, other covariance matrices, such as compound symmetry or 
autoregressive, will be considered. From this analysis, the LS mean, SE, and 2-sided 90% CIs 
will be calculated for the contrast “moxifloxacin versus placebo” at each post-baseline time point 
on Day 1, respectively. 
For HR, PR, QRS intervals, the analysis will be based on the change-from-baseline post-dosing 
values (ΔHR, ΔPR, and ΔQRS). The same (by-time point analysis) model will be used as 
described for QTcF. The LS mean, SE, and 2-sided 90% CI from the statistical modeling for 
both change-from- baseline and placebo-corrected change-from-baseline values will be listed in 
the tables and graphically displayed. 
The SAS code for the by-time point analysis for QTcF for CBP-307 versus placebo is as follows. 
PROC MIXED DATA=ECG; 
CLASS SUBJID TREAT TIME; 
MODEL DQTc=TREAT TIME TREAT*TIME BASE/DDFM=KR;  
REPEATED TIME / SUBJECT = SUBJID type = UN; 
LSMEANS TREAT*TIME/CL DIFF ALPHA=0.1;  
RUN; 
 
Where ECG = QT/QTc population, SUBJID = subject number, TREAT = treatment (dose of CBP-307 on Day 1, on 
Day 6, and on Day 15, and corresponding placebo), TIME = nominal post-baseline time point, BASE = baseline 
QTcF, and DQTc = ΔQTcF. 
 
The SAS code for the by-time point analysis for QTcF for moxifloxacin versus placebo is as 
follows. 
PROC MIXED DATA=ECG; 
CLASS SUBJID TREAT TIME PERIOD SEQUENCE; 
MODEL DQTc=TREAT TIME TREAT*TIME PERIOD SEQUENCE BASE/DDFM=KR;  
RANDOM INTERCEPT / SUBJECT =SUBJID TYPE=UN; 
REPEATED TIME / SUBJECT = PERIOD*SUBJID TYPE = UN; 
LSMEANS TREAT*TIME/CL DIFF ALPHA=0.1;  
RUN; 
 
Where ECG = QT/QTc population, SUBJID = subject number, TREAT = treatment (moxifloxacin and placebo), 
TIME = nominal post-baseline time point, PERIOD= period, SEQUENCE = sequence, BASE = baseline QTcF, and 
DQTc = ΔQTcF. 
6.4 Categorical Analysis 
Results for categorical outliers will be summarized in frequency tables with counts and 
percentages for both number of subjects and number of time points. Subject data will be 
summarized using the count of distinct subjects that fall into the category and the percentage of 
the total number of subjects. Time point data will be summarized using the count of time points 
at which the assessments fall into the category and the percentage of the total number of time 


 
 
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points at which assessments are performed. Counts (either number of subjects or number of time 
points) for each treatment group will be used as the denominator in the calculation of 
percentages unless otherwise specified. 
A subject or time point will be determined as an outlier if the following criteria (which are 
assessed separately) are met for the ECG intervals (Table 5). 
Table 5 
Criteria for determining a subject or time point outlier 
ECG 
interval 
Categorical outlier criteria 
QTcF 
Treatment-emergent value of > 450 and ≤ 480 ms when not present at baseline 
(new onset) 
Treatment-emergent value of > 480 and ≤ 500 ms when not present at baseline 
(new onset) 
Treatment-emergent value of > 500 ms when not present at baseline (new onset) 
Increase of QTc from baseline of > 30 and ≤ 60 ms 
Increase of QTc from baseline > 60 ms 
PR 
Increase of PR from baseline > 25% resulting in PR > 200 ms 
QRS 
Increase of QRS from baseline > 25% resulting in QRS > 120 ms 
HR 
Decrease of HR from baseline >25% resulting in HR < 50 bpm 
Increase of HR from baseline >25% resulting in HR > 100 bpm 
All outliers will be summarized for each treatment on the basis of incidence rates. A subject will 
be counted only once for a particular outlier event if the subject experiences more than 1 episode 
of that event. The total number of time points will be based on the number of observed time 
points across all subjects within a treatment group. 
6.5 Morphological analysis for T-wave and U-wave 
Morphological analyses will be performed with a focus on detecting changes in T-wave 
morphology and appearance of abnormal U-waves. The analyses will evaluate change-from-
baseline (i.e., treatment-emergent changes). For each category of T-wave morphology and of U 
waves, the category will be deemed as present if observed in any replicates at the time point. For 
baseline, the category will be deemed as present if observed in any replicates from all time points 
that constitute baseline.   
The analysis results for T-wave morphology and U-wave presence will be summarized in 
frequency tables with counts and percentages for both number of subjects and number of time 
points. The number and percentage of subjects in each treatment group having changes from 
baseline that represent the appearance of the morphological abnormality will be also 
summarized. The total number of time points having a particular change event will be 
summarized in terms of number and percentage based on the number of observed time points 
across all subjects within a treatment group. 


 
 
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6.6 Determination of Sample Size 
Approximately 68 healthy subjects (at least 30% for each sex) will be randomized 
into 2 groups (Group 1 and 2) with 34 subjects in each. Group 2 consists of 2 sub-
groups (Group 2A and 2B) and each sub-group will be randomized with 17 subjects. 
Determination of sample size for primary analysis 
A sample size of 28 evaluable subjects per treatment group will provide more than 94.4% 
power to exclude that CBP-307 causes more than 10-ms QTc effect at clinically relevant 
plasma levels, as shown by the upper bound of the 2-sided 90% confidence interval (CI) of 
the model-predicted QT effect (ΔΔQTcF) at the observed geometric mean Cmax of CBP-
307 in the study. This power is estimated approximately using a 2-sample t-test. The 
calculation assumes a 1-sided 5% significance level, an underlying effect of CBP-307 of 
3 ms and a standard deviation (SD) of the ΔQTcF of 8 ms for both CBP-307 and placebo 
treatment groups. Note that this calculation is conservative, since it does not take into 
account any gain in precision due to the use of all data of each subject with the help of a 
linear mixed-effects model. The concentration-QTc analysis method is supported by Darpo 
et al5 and Ferber et al6, and consistent with the experiences from 25 recent TQT studies. 
Determination of sample size for assay sensitivity analysis 
To demonstrate assay sensitivity with concentration-QTc analysis, it has to be shown that 
the ΔΔQTcF of a single dose of 400 mg moxifloxacin exceeds 5 ms (i.e., the lower bound of 
the 2-sided 90% CI of the predicted QTc effect [ΔΔQTcF] should exceed 5 ms). In a 
similarly designed, recent crossover study with 24 healthy subjects (on-file data, ERT), the 
standard error (SE) for the prediction of the QT effect of moxifloxacin based on the 
exposure-response analysis was 1.24 ms. The within-subject SD of ΔQTcF in the referred 
study was 5.4 ms based on the by-time point analysis. If the effect of moxifloxacin is 
assumed to be 10 ms, the SE of 1.24 ms corresponds to an effect size of (10-
5)/(1.24×sqrt[24])=0.82, where the effect size is the effect assumed under the alternative 
hypothesis divided by the SD of the test variable. This value should be compared to the 
effect size of 0.64 required to guarantee a power of at least 95% in a paired t-test situation 
with a sample size of 28 evaluable subjects. In other words, based on this calculation, a 
power of at least 95% will be obtained as long as the variability of the ΔQTcF, as measured 
by its within-subject SD from the by-time point analysis, does not exceed 6.9 ms (ie, 128% 
[= 0.82/0.64] of the 5.4 ms observed in the referred study assuming the ratio of effective 
sizes is consistent with inverse ratio of within-subject SD). The number also agrees with 
recent recommendations of the FDA, which propose at least 20 subjects (Huang et al7). 
 
 
 


 
 
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7 References 
1. Garnett C, Bonate PL, Dang Q, Ferber G, Huang D, Liu J, et al. Scientific white paper on 
concentration-QTc modeling. [Published correction appears in J Pharmacokinet 
Pharmacodyn. 2018;45(3):399]. J Pharmacokinet Pharmacodyn. 2018;45(3):383-397. 
2. Tornøe CW, Garnett CE, Wang Y, Florian J, Li M, Gobburu JV. Creation of a knowledge 
management system for QT analyses. J Clin Pharmacol. 2011;51(7):1035-1042. 
3. Cleveland WS. Robust locally weighted regression and smoothing scatterplots. J Am Stat 
Assoc. 1979;74(368):829-836. 
4. Hurvich CM, Simonoff JS, and Tsai CL. Smoothing parameter selection in nonparametric 
regression using an improved Akaike Information Criterion. J R Stat Soc Series B Stat 
Methodol. 1998;60(2):271-293. 
5. Darpo B, Benson C, Dota C, et al. Results From the IQ-CSRC Prospective Study Support 
Replacement of the Thorough QT Study by QT Assessment in the Early Clinical Phase. Clin 
Pharmacol Ther. 2015;97(4):326-335. 
6. Ferber G, Zhou M, and Darpo B. Detection of QTc Effects in Small Studies--Implications for 
Replacing the Thorough QT Study. Ann Noninvasive Electrocardiol. 2015;20(4):368-377. 
7. Huang DP, Chen J, Dang Q, and Tsong Y: Assay sensitivity in “Hybrid thorough QT/QTc 
(TQT)” study, Journal of Biopharmaceutical Statistics, 2019; 29(2), 378-384. 
8 Tables, Figures, and Listings 
8.1 Tables 
Number 
Title 
Comments 
14.1.1.1 
Baseline values of ECG 
parameters with descriptive 
statistics for CBP-307 analysis 
n, mean, SD, 90% CI, median, minimum, and 
maximum from descriptive summary will be 
given by treatment for each ECG parameter 
(Section 5.3). 
14.1.1.2 
Baseline values of ECG 
parameters with descriptive 
statistics for moxifloxacin 
analysis 
n, mean, SD, 90% CI, median, minimum, and 
maximum from descriptive summary will be 
given by treatment for each ECG parameter 
(Section 5.3). 
14.1.2.1 
Observed values of QTcF with 
descriptive statistics for CBP-
307 analysis 
n, mean, SD, 90% CI, median, minimum, and 
maximum from descriptive statistics will be 
given by treatment and post-baseline time 
point (Section 6.3).  
14.1.2.2 
Observed values of QTcF with 
descriptive statistics for 
moxifloxacin analysis 
n, mean, SD, 90% CI, median, minimum, and 
maximum from descriptive statistics will be 
given by treatment and post-baseline time 
point (Section 6.3). 


 
 
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Number 
Title 
Comments 
14.1.3.1-
14.1.3.4 
Change-from-baseline QTcF, 
HR, PR, and QRS (ΔQTcF, 
ΔHR, ΔPR, and ΔQRS) at each 
time point for CBP-307 analysis 
n, LS mean, SE, and 90% CI from the 
statistical modeling will be given by 
treatment and time point (Section 6.3). 
14.1.4.1-
14.1.4.4 
Change-from-baseline QTcF, 
HR, PR, and QRS (ΔQTcF, 
ΔHR, ΔPR, and ΔQRS) at each 
time point for moxifloxacin 
analysis 
n, LS mean, SE, and 90% CI from the 
statistical modeling will be given by 
treatment and time point (Section 6.33). 
14.1.5.1-
14.1.5.4 
Placebo-corrected change-from-
baseline QTcF, HR, PR, and 
QRS (ΔΔQTcF ΔΔHR, ΔΔPR, 
and ΔΔQRS) at each time point 
for CBP-307 analysis 
LS mean, SE, and 90% CI from the statistical 
modeling will be given by treatment and time 
point (Section 6.33). 
14.1.6.1-
14.1.6.4 
Placebo-corrected change-from-
baseline QTcF, HR, PR, and 
QRS (ΔΔQTcF, ΔΔHR, ΔΔPR, 
and ΔΔQRS) at each time point 
for moxifloxacin analysis 
LS mean, SE, and 90% CI from the statistical 
modeling will be given by treatment and time 
point (Section 6.33). 
14.1.7.1 
QTcF outliers per absolute 
category for CBP-307 analysis 
Number (%) of subjects and time points with 
QTcF > 450 and ≤ 480 ms, > 480 and ≤ 500 
ms, or > 500 ms by treatment (Section 6.4).  
14.1.7.2 
QTcF outliers per absolute 
category for moxifloxacin 
analysis 
Number (%) of subjects and time points with 
QTcF > 450 and ≤ 480 ms, > 480 and ≤ 500 
ms, or > 500 ms by treatment (Section 6.44). 
14.1.8.1 
QTcF outliers per change-from-
baseline category for CBP-307 
analysis 
Number (%) of subjects and time points with 
QTcF > 30 and ≤ 60 ms, or > 60 ms by 
treatment (Section 6.4).  
14.1.8.2 
QTcF outliers per change-from-
baseline category for 
moxifloxacin analysis 
Number (%) of subjects and time points with 
QTcF > 30 and ≤ 60 ms, or > 60 ms by 
treatment (Section 6.44). 
14.1.9.1 
Categorical analyses for HR, 
PR, and QRS for CBP-307 
analysis 
Number (%) of subjects and time points with 
PR > 25% and PR > 200 ms at post-dose; 
QRS > 25% and QRS > 120 ms at post-
dose; HR decrease from baseline > 25% and 
HR < 50 bpm at post-dose; and HR increase 
from baseline > 25% and HR > 100 bpm at 
post-dose (Section 6.4). 


 
 
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Number 
Title 
Comments 
14.1.9.2 
Categorical analyses for HR, 
PR, and QRS for moxifloxacin 
analysis 
Number (%) of subjects and time points with 
PR > 25% and PR > 200 ms at post-dose; 
QRS > 25% and QRS > 120 ms at post-
dose; HR decrease from baseline > 25% and 
HR < 50 bpm at post-dose; and HR increase 
from baseline > 25% and HR > 100 bpm at 
post-dose (Section 6.4). 
14.1.10.1 
T-wave morphology and U-
wave presence across treatment 
groups: treatment-emergent 
changes for CBP-307 analysis 
Number (%) of subjects and time points 
falling into each of the T-wave and U-wave 
categories will be given by treatment 
(Section 6.5). 
14.1.10.2 
T-wave morphology and U-
wave presence across treatment 
groups: treatment-emergent 
changes for moxifloxacin 
analysis 
Number (%) of subjects and time points 
falling into each of the T-wave and U-wave 
categories will be given by treatment 
(Section 6.55). 
14.1.11.1 
Concentration-QTc analysis of 
CBP-307 and associated 
ΔQTcF prolongation  
Fixed-effect estimations and corresponding 
P values will be given (Section 6.1). 
14.1.11.2 
Assay sensitivity analysis of 
moxifloxacin and associated 
ΔQTcF prolongation 
Fixed effect estimations and corresponding 
P values will be given (Section 6.2). 
14.1.12.1 
Predicted ΔΔQTcF interval at 
geometric mean peak CBP-307 
concentration 
Section 6.1. Referred to above as a 
“Concentration-QTc prediction table.” 
14.1.12.2 
Predicted ΔΔQTcF interval at 
geometric mean peak 
moxifloxacin concentration 
Section 6.2. Referred to above as a 
“Concentration-QTc prediction table.” 
 
8.2 Figures 
Number 
Title 
Comments 
14.2.1.1 
Observed QTcF across time 
points for CBP-307 analysis 
Mean and 90% CI from descriptive summary 
will be given by treatment (Section 6.33).  
14.2.1.2 
Observed QTcF across time 
points for moxifloxacin analysis 
Mean and 90% CI from descriptive summary 
will be given by treatment (Section 6.33). 
14.2.2.1-
14.2.2.4 
Change-from-baseline QTcF, 
HR, PR, and QRS (ΔQTcF, 
ΔHR, ΔPR, and ΔQRS) across 
time point for CBP-307 analysis 
LS mean and 90% CI from the statistical 
modeling will be shown by treatment 
(Section 6.3). 


 
 
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Number 
Title 
Comments 
14.2.3.1-
14.2.3.4 
Change-from-baseline QTcF, 
HR, PR, and QRS (ΔQTcF, 
ΔHR, ΔPR, and ΔQRS) across 
time point for moxifloxacin 
analysis 
LS mean and 90% CI from the statistical 
modeling will be shown by treatment 
(Section 6.3). 
14.2.4.1-
14.2.4.4 
Placebo-corrected change-from-
baseline QTcF, HR, PR, and 
QRS (ΔΔQTcF, ΔΔHR, ΔΔPR, 
and ΔΔQRS) across time point 
for CBP-307 analysis 
LS mean and 90% CI from the statistical 
modeling will be shown by treatment 
(Section 6.33). 
14.2.5.1-
14.2.5.4 
Placebo-corrected change-from-
baseline QTcF, HR, PR, and 
QRS (ΔΔQTcF, ΔΔHR, ΔΔPR, 
and ΔΔQRS) across time point 
for moxifloxacin analysis 
LS mean and 90% CI from the statistical 
modeling will be shown by treatment 
(Section 6.33). 
14.2.6.1 
Scatter plot of QTcF versus RR 
by treatment  
Scatter plots of QTcF and RR intervals by 
treatment with regression lines will be given 
(Section 5.4).  
14.2.6.2 
QTcF-RR decile plot by 
treatment  
QTcF-RR decile plots with linear mixed-
effects line and 90% CI will be given 
(Section 5.4).  
14.2.7.1 
Mean CBP-307 plasma 
concentrations over time  
Section 6.1. 
14.2.7.2 
Mean moxifloxacin plasma 
concentration over time 
Section 6.2. 
14.2.8.1-
14.2.8.3 
CBP-307 plasma concentrations 
and ΔΔQTcF over time 
Section 6.1.1.  
14.2.9.1-
14.2.9.3 
Hysteresis plot of CBP-307 
plasma concentration and 
ΔΔQTcF connected in temporal 
order  
Section 6.1.1.  
14.2.10.1 
Scatter plot of observed CBP-
307 plasma concentrations and 
ΔQTcF with simple linear 
regression line and LOESS 
regression  
Scatter plot of observed QTcF versus 
concentration with LOESS line and 90% CI 
and simple regression line (Section 6.1.2). 
14.2.10.2 
Scatter plot of observed 
moxifloxacin plasma 
concentrations and ΔQTcF with 
simple linear regression line 
and LOESS regression 
Scatter plot of QTcF versus concentration 
with LOESS line and 90% CI and simple 
regression line (Section 6.2). 


 
 
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Number 
Title 
Comments 
14.2.11.1 
Scatter plot of observed CBP-
307 plasma concentrations and 
estimated placebo-adjusted 
ΔQTcF  
Scatter plot of placebo-adjusted QTcF 
versus concentration with linear mixed-
effects regression line and 90% CI of 
ΔΔQTcF (Section 6.1). Referred to above as 
“Scatter plot for concentration-QTc 
model(s).” 
14.2.11.2 
Scatter plot of observed 
moxifloxacin plasma 
concentrations and estimated 
placebo-adjusted ΔQTcF 
Scatter plot of placebo-adjusted QTcF 
versus concentration with linear mixed-
effects regression line and 90% CI of 
ΔΔQTcF (Section 6.2). Referred to above as 
“Scatter plot for concentration-QTc 
model(s).” 
14.2.12.1 
Model-predicted ΔΔQTcF 
(mean and 90% CI) and 
estimated placebo-adjusted 
ΔQTcF (mean and 90% CI) 
across deciles of  
CBP-307 plasma concentrations 
Section 6.1. Referred to above as “Decile 
plots.” 
14.2.12.2 
Model-predicted ΔΔQTcF 
(mean and 90% CI) and 
estimated placebo-adjusted 
ΔQTcF (mean and 90% CI) 
across deciles of moxifloxacin 
plasma concentrations  
Section 6.2. Referred to above as “Decile 
plots.” 
14.2.13.1 
Model-predicted ΔΔQTcF 
interval at geometric mean peak 
CBP-307 concentrations 
Section 6.1. Referred to above as “Prediction 
plots.” 
14.2.13.2 
Model-predicted ΔΔQTcF 
interval (mean and 90% CI) at 
geometric mean peak 
moxifloxacin concentrations  
Section 6.2. Referred to above as “Prediction 
plots.” 
14.2.14.1 
Scatter plot of standardized 
residuals versus fitted values for 
CBP-307  
Section 6.1.2.  
14.2.14.2 
Scatter plot of standardized 
residuals versus fitted values for 
moxifloxacin 
Section 6.2. 
14.2.15.1 
Scatter plot of standardized 
residuals versus concentrations 
with LOESS for CBP-307  
Section 6.1.2. 


 
 
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Number 
Title 
Comments 
14.2.15.2 
Scatter plot of standardized 
residuals versus concentrations 
with LOESS for moxifloxacin 
Section 6.2. 
14.2.16.1 
Scatter plot of standardized 
residuals versus centered 
baseline QTcF with LOESS for 
CBP-307 
Section 6.1.2. 
14.2.16.2 
Scatter plot of standardized 
residuals versus centered 
baseline QTcF with LOESS for 
moxifloxacin 
Section 6.2.  
14.2.17.1 
Box plot of standardized 
residuals versus nominal time 
for CBP-307  
Section 6.1.2. 
14.2.17.2 
Box plot of standardized 
residuals versus nominal time 
for moxifloxacin 
Section 6.2. 
14.2.18.1 
Box plot of standardized 
residuals versus treatment for 
CBP-307  
Section 6.1.2. 
14.2.18.2 
Box plot of standardized 
residuals versus treatment for 
moxifloxacin 
Section 6.2. 
14.2.19.1 
Normal Q-Q plot of 
standardized residuals for CBP-
307  
Section 6.1.2. 
14.2.19.2 
Normal Q-Q plot of 
standardized residuals for 
moxifloxacin 
Section 6.2. 
14.2.20.1 
Normal Q-Q plots of the 
estimated random effects for 
CBP-307  
Section 6.1.2. 
14.2.20.2 
Normal Q-Q plots of the 
estimated random effects for 
moxifloxacin 
Section 6.2. 
 


 
 
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8.3 Listings 
Number 
Title 
Comments 
16.2.1.1.1-
16.2.1.1.4 
QTcF, HR, PR, and QRS 
intervals - observed and 
change-from-baseline values for 
CBP-307 analysis 
Section 6.33 for CBP-307 analysis. 
16.2.1.2.1-
16.2.1.2.4 
QTcF, HR, PR, and QRS 
intervals - observed and 
change-from-baseline values for 
moxifloxacin analysis 
Section 6.3 for moxifloxacin analysis.  
16.2.2.1 
T-wave morphology and U-
wave presence for CBP-307 
analysis 
Section 6.55 for CBP-307 analysis. 
16.2.2.2 
T-wave morphology and U-
wave presence for moxifloxacin 
analysis 
Section 6.5 for moxifloxacin analysis.  
16.2.3.1 
ΔQTcF and time-matched CBP-
307 concentrations for each 
subject  
Data for concentration-QTc analysis 
(Section 6.1). 
16.2.3.2 
ΔQTcF and time-matched  
moxifloxacin concentrations for 
each subject 
Data for assay sensitivity (Section 6.2). 
 
 
 


 
 
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9 Approvals 
ERT 
 
 
 
 
 
Borje Darpo, MD, PhD 
Chief Scientific Officer, Cardiac Safety 
Date 
 
 
 
 
 
Hongqi Xue, PhD 
Sr. Principal Biostatistician 
Date 
Suzhou Connect Biopharmaceuticals, Ltd. 
 
 
 
 
 
Jessie Chen  
Project Manager 
Date 
 
 
 
 
12-Mar-2022 | 02:57:47 EST
11-Mar-2022 | 16:02:31 EST
13-Mar-2022 | 19:48:41 PDT


 
 
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Appendix A: Early Precision QT Analysis 
Twelve-lead ECGs will be extracted in up to 10 replicates from each nominal time point pre-
specified in the protocol. The median value of each parameter from the set of evaluable beats in 
each extracted replicate will be calculated, and then the mean of all available medians (minimum 
3 medians) from the nominal time point will be used as the subject’s reportable value at that time 
point. 
Early Precision QT analysis (formerly High Precision QT analysis) will be performed on all 
analyzable (non-artifact) beats in the 10 ECG replicates (1 replicate consists of one 14 second 
ECG). Statistical quality control procedures will be used to review and assess all beats and 
identify “high” and “low” confidence beats using several criteria including: 
 QT or QTc values exceeding or below certain thresholds (biologically unlikely) 
 RR values exceeding or below certain thresholds (biologically unlikely) 
 Rapid changes in QT, QTc, or RR from beat to beat 
Placement of fiducials and measurements of all primary ECG parameters (QT, QTc, RR) in all 
recorded beats of all replicates will be performed using the iCOMPAS software. All beats that 
are deemed “high confidence” will not be reviewed by an ERT cardiac safety specialist. All low 
confidence beats will be reviewed manually by an ERT cardiac safety specialist and adjudicated 
using pass-fail criteria. The beats found acceptable by manual review will be included in the 
analysis. The beats confirmed to meet fail criteria will not be included in the analysis. 
For the purpose of measuring PR and QRS intervals and to assess T-wave morphology and 
presence of U-waves, the TQT Plus algorithm will select the 3 ECG replicates with the highest 
quality score from the ECG extraction window. These 3 ECGs will be analyzed using a semi-
automated process to determine these parameters. If 3 consecutive usable beats cannot be 
identified in at least 2 of the 3 replicates, then all beats in all replicates will be reviewed for that 
time point using a manual analysis. 
If manual analysis is required, then all beats in a minimum of 3 replicates will be reviewed using 
the iCOMPAS software. The ERT cardiac safety specialist will review all usable beats in Lead II 
(or an alternate lead) for each replicate and will review and/or adjust the fiducial placements 
(onset of P, onset of Q, offset of S, and offset of T-wave that were electronically marked) of each 
waveform and also document the T-wave morphology and the presence of U-waves for each 
beat. A replicate will only be reported if it has 3 approved, usable beats. 


Clinical Study Report 
CONFIDENTIAL 
Labcorp Drug Development Study: 8463245 
Protocol Reference: CBP-307AU002  
 
16.1.9.2. 
Quality Tolerance Limit Definitions 
Parameter 
Justification for Parameter 
Unit Tolerance 
Minimum number of evaluable 
subjects needed. 
A shortfall in the overall number of 
subjects could have had a significant 
impact on interpretation of the primary 
endpoint because of limited/insufficient 
exposure. 
N:64