Clinical trial NCT05105243
Conditions: Safety Issues Tolerance
Keywords: PK Efficacy
Sponsor: Cerevance
Start date: 2022-01-17; Completion date: 2022-11-21
Enrollment: 64 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN766 in Healthy participants.

Detailed description:
Study Design:

This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in healthy participants with concurrent pharmacokinetic (PK) sampling from blood plasma, urine, and cerebrospinal fluid. The overall study design is outlined below:

Part 1: Single-Dose Regimen and Fasted-Fed Crossover. For the single-dose regimen, approximately 40 healthy male or female participants will be enrolled in 1 of 5 single-dose cohorts (designated as S1 through S5, respectively) in an ascending fashion. Each cohort will consist of 8 participants randomized to CVN766 or placebo, whereby 6 participants will receive a single oral dose of CVN766 suspension, and 2 participants will receive a matching placebo suspension under overnight fasted conditions. Participants will remain fasted for 4 hours post-dose. Consumption of water is permitted as desired except for 1 hour before and after administration of Study Drug. Sentinel dosing (1 participant to receive CVN766 and 1 participant to receive placebo) will be used in each cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 or placebo to the remainder of participants within the cohort. After blinded review by the Safety Review Group (SRG) of 24-hours, post-dose safety and tolerability data from the sentinel group, the remaining 6 participants of each cohort may be dosed provided that the adverse event (AE) profile in the first 2 participants is considered acceptable. To accommodate the lumbar puncture in the S3 fasted cohort, after the sentinel group, the remaining 6 participants dosing may be staggered every two days. The planned dose levels will be 5, 15, 45, 125, and 250 mg CVN766. The SRG will review all available blinded safety, tolerability, clinical laboratory results (minimally including samples collected from participants through 72-hours post-dose), and PK data after each cohort and before subsequent dose escalation. Each following dose level may be higher, lower, or remain the same as the preceding cohort, dependent on the recommendation of the SRG.

Additional cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety and tolerability of CVN766. For example, if the maximum tolerated dose (MTD) is not reached with cohort S5, additional cohorts with higher dose levels may be considered. Such additional cohorts will follow the same schedule of events as cohorts S1 through S5. Additional/alternative PK timepoints may be implemented if the SRG determines this is necessary to fully characterize the PK profile of CVN766.

To assess the effect of food on CVN766 bioavailability in suspension formulation, single-dose administration will be repeated in a single cohort (S3) after ingestion of a standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Dec 2002). Once the safety of the S3 cohort dose level has been assessed, the S3 cohort participants will return to the clinic (no sooner than 14 days after their prior dose, or at least 4 half-lives, has lapsed based on preliminary PK data, whichever is longer). They will receive the same dose as before, administered after ingesting a standardized breakfast. Participants will finish the entire content of their breakfast within 25 minutes and will receive CVN766 30 minutes (± 5 minutes) after beginning the meal. Sentinel dosing will not be required for participants returning to the clinic for the fed regimen. If the CVN766 PK parameters in the fasted S3 cohort reveal poor absorption with inconclusive results, the fed cohort will be deferred until a higher dose level.

Participants for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit for safety and PK assessments. On Day 1, participants will undergo safety monitoring and PK sampling from blood plasma through 72 hours post-dose and, for cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. The total confinement period will be 4 nights, unless extended at the discretion of the Investigator, e.g., for monitoring and/or management of AEs. Follow-up assessments will occur on approximately Days 8 and 14 and +21 and +28 for cohort S3.

Part 2: Multiple-Dose Regimen. For the multiple-dose regimen, approximately 24 healthy male and female participants age 18 to 50 years old will be enrolled in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. The dose levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-dose cohorts M1 through M3, respectively. Each multiple-dose cohort will consist of 8 participants randomized to CVN766 or placebo, whereby 6 participants will receive a daily oral dose of CVN766, and 2 participants will receive a matching placebo for 7 days. Dosing will be administered in the fasting state; this can be changed by the SRG if exposure is found to be higher in the fed state. The planned dosing duration for the multiple-dose cohorts is 7 days. However, the duration may be increased to ≤14 days at the discretion of the SRG if preliminary PK data suggests steady-state will not be achieved within 6 days of daily dosing. For each dose on intensive PK sampling days (first and last days of dosing, e.g., Days 1 and 7), participants will remain fasted for 4 hours post-dose. On other dosing days (Days 2-6), participants will remain fasted for 1-hour post-dose. Consumption of water is permitted as desired except for 1 hour before and after administration of Study Drug. Unlike the single-dose regimen, sentinel dosing within cohorts is not required in the multiple-dose regimen.

Initiation of the multiple-dose regimen will only occur after a full blinded review of all safety, tolerability, and clinical laboratory results for the fasting drug administration to single-dose Cohort S3 (minimally including samples collected through Day 4) and available PK data. For each multiple-dose cohort after the first, the actual choice of dose level may be modified by the SRG after the available blinded safety, tolerability, clinical laboratory results, and PK data in the preceding multiple-dose and corresponding single-dose cohorts (i.e., multiple-dose Cohort M2 will not initiate until the data review for multiple-dose Cohort M1 and single-dose cohort S4 is complete). Each subsequent dose level may be higher, lower, or remain the same as the preceding.

Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety and tolerability of CVN766. Such additional cohorts will follow the same schedule of events as for prior multiple-dose cohorts. Additional/alternative PK timepoints may be implemented if the SRG determines this is necessary to fully characterize the PK profile of CVN766.

Participants for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit for the duration of the dosing period and for at least 48 hours after the last dose for safety and PK assessments before discharge. On treatment Days 1 and 7, participants will undergo safety monitoring and PK sampling from blood plasma through 48 hours post-dose and, in cohort M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, on treatment Day 7 (or last day of dosing, if extended beyond Day 7), participants will undergo additional PK sampling from CSF via lumbar puncture at 3 hours post-dose. If necessary to resolve questions arising from prior cohorts' data, participants in cohort M3 may also, at SRG discretion, undergo PK sampling from CSF via lumbar puncture, with the choice of day (e.g., Day 1 or Day 7) and sampling time to be decided by SRG. Participants in MAD cohorts may be asked to return to the clinic for an additional PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK data, (i.e., t½). The total confinement period will be 9 nights unless extended for additional dosing days or management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final dose.

Arms: arm 1: Each dose cohort: 8 participants (6 active:2 placebo). 5 mg. arm 2: Each dose cohort: 8 participants (6 active:2 placebo). 15 mg. arm 3: Each dose cohort: 8 participants (6 active:2 placebo). 45 mg. arm 4: Each dose cohort: 8 participants (6 active:2 placebo). 125 mg. arm 5: Each dose cohort: 8 participants (6 active:2 placebo). 250 mg. arm 6: Each dose cohort: 8 participants (6 active:2 placebo). 45mg. arm 7: Each dose cohort: 8 participants (6 active:2 placebo). 125 mg. arm 8: Each dose cohort: 8 participants (6 active:2 placebo). 250 mg.
Interventions: intervention 1: CVN766
Intervention descriptions: intervention 1: highly selective orexin-1 receptor (Ox1R) antagonist

Protocol documents:
Prot_000.pdf: 
CVN766 
Study No. CVN766-101 
Page 1 of 81
Clinical Protocol  - Final  Version 1.0 
September 2021
CONFIDENTIAL 
PROTOCOL 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, 
Tolerability, and Pharmacokinetic Study of Escalating Single and 
Multiple Doses of CVN766 
in Healthy Subjects  
Short Title: Phase 1 SAD/MAD Study of CVN766 
Sponsor: 
Cerevance Gamma, Inc. 
One Marina Park Drive, Suite 1410 
Boston, MA 02210 
Study Number: 
CVN766-101 
IND Number: 
Not Applicable 
EudraCT Number: 
Not Applicable 
Compound: 
CVN766 
Protocol Version: 
1.0 
Date: 
24 September 2021 
CONFIDENTIAL PROPERTY OF CEREVANCE 
This document is a confidential communication of Cerevance Gamma, Inc. (“Cerevance”). Acceptance of this 
document constitutes the agreement by the recipient that no information contained herein will be published or 
disclosed without written authorization from Cerevance except to the extent necessary to obtain informed consent 
from those persons to whom the drug may be administered. Furthermore, the information is only meant for review 
and compliance by the recipient, his or her staff, and applicable institutional review committee and regulatory 
agencies to enable the conduct of the study. 
 
 
 
 
 
NCT Number: NCT05105243 
 
This NCT number has been applied to the document for purposes of posting on Clinicaltrials.gov


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CVN766 
 
Study No. CVN766-101 
Page 4 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
INVESTIGATOR AGREEMENT  
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, and 
any other product information provided by the sponsor. I agree to conduct this study in 
accordance with the requirements of this protocol and also to protect the rights, safety, privacy, 
and well-being of study subjects in accordance with the following: 
• The ethical principles that have their origin in the Declaration of Helsinki 
• International Council on Harmonisation, E6 GCP: Consolidated Guideline 
• All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations 
• Regulatory requirements for reporting serious adverse events (SAEs) defined in Section 9.9 
of this protocol 
• Terms outlined in the Clinical Study Site Agreement 
• Appendix B – Responsibilities of the Investigator 
 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix C of this protocol. 
Signature of Investigator 
Date 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State/Provence) 
Location of Facility (Country) 
 


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CVN766 
 
Study No. CVN766-101 
Page 9 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
2.0 
STUDY SUMMARY 
Name of Sponsor(s): 
Cerevance, Inc. 
Compound: 
CVN766
 
Title of Protocol: A Phase 1, Randomized, Double-Blind, 
Placebo-Controlled, Safety, Tolerability, and 
Pharmacokinetic Study of Escalating Single and Multiple 
Doses of CVN766 in Healthy Subjects  
IND No.:  
EudraCT No.: 
Not Applicable 
Study Number: CVN766-101 
Phase: 1 
Study Design: 
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in 
healthy subjects with concurrent PK sampling from blood plasma, urine, and cerebrospinal fluid. The overall study 
design is outlined below: 
  
Part 1: Single-Dose Regimen and Fasted-Fed Crossover 
For the single-dose regimen, approximately 40 healthy male or female subjects will be enrolled in 1 of 5 single-dose 
cohorts (designated as S1 through S5, respectively) in an ascending fashion. Each cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a single oral dose of CVN766 suspension, and 
2 subjects will receive a matching placebo suspension under overnight fasted conditions. Subjects will remain fasted 
for 4 hours post-dose. Consumption of water is permitted as desired except for 1 hour before and after administration 
of Study Drug. Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in each 
cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 or placebo to the 
remainder of subjects within the cohort. After blinded review by the Safety Review Group (SRG) of 24-hour, post-
dose safety and tolerability data from the sentinel group, the remaining 6 subjects of each cohort may be dosed 
provided that the adverse event (AE) profile in the first 2 subjects is considered acceptable. To accommodate the 
lumbar puncture in the S3 fasted cohort, after the sentinel group, the remaining 6 subjects dosing may be staggered 
every two days. The planned dose levels will be 5, 15, 45, 125, and 250 mg CVN766.  The SRG will review all 
available blinded safety, tolerability, clinical laboratory results (minimally including samples collected from 
subjects through 72-hours post-dose), and pharmacokinetic (PK) data after each cohort and before subsequent dose 
escalation. Each following dose level may be higher, lower, or remain the same as the preceding cohort, dependent 
on the recommendation of the SRG.  
Additional cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety and tolerability 
of CVN766. For example, if cohort S5 is well-tolerated, additional cohorts with higher dose levels may be 
considered. Such additional cohorts will follow the same schedule of events as for cohorts S1 through S5. 
Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary to fully 
characterize the PK profile of CVN766. 
To assess the effect of food on CVN766 bioavailability in suspension formulation, the single-dose administration 


CVN766 
 
Study No. CVN766-101 
Page 10 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
will be repeated in a single cohort (S3) after ingestion of a standardized high-fat, high-calorie meal according to 
FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Dec 2002). Once the safety 
of the S3 cohort dose level has been assessed, the S3 cohort subjects will return to the clinic (no sooner than 14 days 
after their prior dose, or at least 4 half-lives, has lapsed based on preliminary PK data, whichever is longer). They 
will receive the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish the 
entire content of their breakfast within 25 minutes and will receive an investigational product 30 minutes (± 5 
minutes) after beginning the meal. Sentinel dosing will not be required for subjects returning to the clinic for the fed 
regimen. If the CVN766 PK parameters in the fasted S3 cohort reveal poor absorption with inconclusive results, the 
fed cohort will be deferred until a higher dose level.    
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit for safety and 
PK assessments. On Day 1, subjects will undergo safety monitoring and PK sampling from blood plasma through 
72 hours post-dose and, for cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. The total 
confinement period will be 4 nights, unless extended at the discretion of the Investigator, e.g., for monitoring and/or 
management of AEs. Follow-up assessments will occur on approximately Days 8 and 14 and +21 and +28 for cohort 
S3. 
A summary of the single-dose regimen visit schedule is presented below:  
Screening a 
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b 
Inpatient PK,  
Safety and 
Lumbar 
Puncture Site 
Assessments 
(S3 fasted) 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
 
Day -28 to -2 
Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14 
±2 days 
 
(a) Screening will occur at study entry. S3 subjects returning for the “Fed” repetition of the single-dose 
regimen will not undergo Screening assessments except as required at Day -1. 
(b) CSF collection will apply only to cohort S3 (fasted). 
(c) Discharge from the clinic may be delayed if necessary, to continue monitoring for resolution of AEs. 
(d) The final follow-up assessment will occur by telephone unless abnormal, clinically significant (CS) 
findings were observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
 
Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 healthy male and female subjects age 18 to 50 years old will be 
enrolled in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. 
The dose levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-
dose cohorts M1 through M3, respectively. Each multiple-dose cohort will consist of 8 subjects randomized to 
CVN766 or placebo, whereby 6 subjects will receive a daily oral dose of CVN766, and 2 subjects will receive a 
matching placebo for 7 days. Dosing will be administered in the fasting state; this can be changed by the SRG if 
exposure is found to be higher in the fed state. The planned dosing duration for the multiple-dose cohorts is 7 days. 
However, the duration may be increased to ≤14 days at the discretion of the SRG if preliminary PK data suggest 
steady-state will not be achieved within 6 days of daily dosing. For each dose on intensive PK sampling days (first 
and last days of dosing, e.g., Days 1 and 7), subjects will remain fasted for 4 hours post-dose. On other dosing days 
(Days 2-6), subjects will remain fasted for 1-hour post-dose. Consumption of water is permitted as desired except 
for 1 hour before and after administration of Study Drug. Unlike the single-dose regimen, sentinel dosing within 
cohorts is not required in the multiple-dose regimen. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all safety, tolerability, and 
clinical laboratory results for the fasting drug administration to single-dose Cohort S3 (minimally including samples 
collected through Day 4) and available PK data. For each multiple-dose cohort after the first, the actual choice of 
dose level may be modified by the SRG after the available blinded safety, tolerability, clinical laboratory results, 


CVN766 
 
Study No. CVN766-101 
Page 11 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
and PK data in the preceding multiple-dose and corresponding single-dose cohorts (i.e., multiple-dose Cohort M2 
will not initiate until the data review for multiple-dose Cohort M1 and single-dose cohort S4 is complete). Each 
subsequent dose level may be higher, lower, or remain the same as the preceding. 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety 
and tolerability of CVN766. Such additional cohorts will follow the same schedule of events as for prior multiple-
dose cohorts.  Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary 
to fully characterize the PK profile of CVN766. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit 
for the duration of the dosing period and for at least 48 hours after the last dose for safety and PK assessments before 
discharge. On treatment Days 1 and 7, subjects will undergo safety monitoring and PK sampling from blood plasma 
through 48 hours post-dose and, in cohort M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, 
on treatment Day 7 (or last day of dosing, if extended beyond Day 7), subjects will additionally undergo PK sampling 
from CSF via lumbar puncture at 3 hours post-dose. If needed to resolve questions arising from prior cohorts’ data, 
subjects in cohort M3 also may, at SRG discretion, undergo PK sampling from CSF via lumbar puncture, the choice 
of day (e.g., Day 1 or Day 7) and sampling time to be decided by SRG. Subjects in MAD cohorts may be asked to 
return to the clinic for an additional PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK 
data, i.e., t½). The total confinement period will be 9 nights unless extended for additional dosing days or 
management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final dose. 
A summary of the multiple-dose regimen visit schedule is presented below: 
Screening 
Inpatient  
Check-in 
Dosing, PK, 
CSF, & Safety 
Assessments  a 
PK / Safety 
Assessments & 
inpatient 
discharge b 
Follow-Up Outpatient 
Visits c 
Follow-Up Call d 
Day -28 to -2 
Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g., 
Days 8-9) 
3 days ±0 after last dose 
(e.g., Day 10) & 
7 days ± 1 after last dose 
(e.g., Day 14) 
14 days ±2 after last 
dose (e.g., Day 21) 
(a) CSF sampling will occur on Day 7 in cohorts M1 and M2. Cohort M3 also may, at SRG discretion, undergo 
PK sampling from CSF, the choice of day and sampling time to be decided by SRG.  
(b) Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or, if 
necessary, to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after last dose (e.g., Day 
10) may be omitted at Investigator’s discretion. 
(d) The Follow-up Visit will occur by telephone unless abnormal, clinically significant (CS) findings are 
observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to ≤14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in cohort M1. 
Safety Review Group (SRG) 
The SRG will be comprised of the Investigator, Medical Monitor, Cerevance Responsible Medical Officer and may 
include other Cerevance representatives. A pharmacokineticist and other subject matter experts may participate as 
needed. The SRG will be responsible for ongoing review of safety, tolerability, and clinical laboratory results, and 
available PK data and deciding: 
1. Expand each single-dose cohort from the sentinel cohort to the entire cohort (based on a review of at least 
24 hours post-dose safety data from each of the sentinel subjects), 
2. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in single-
dose cohorts (based on a review of available data including at least 72 hours post-dose safety data and 
clinical laboratory results from each of the subjects in the current cohort),  
3. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in 
multiple-dose cohorts (based on a review of available data including at least 48 hours post 7th dose safety 


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CVN766 
 
Study No. CVN766-101 
Page 13 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
Main Criteria for Exclusion: 
Subjects have a known hypersensitivity to any component of the formulation of CVN766. Subjects have evidence 
of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, 
urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, psychiatric disorder, or other 
abnormality that may impact the ability of the subject to participate or potentially confound the study results. Any 
finding in the subject’s medical history, physical examination, or safety laboratory tests gives reasonable suspicion 
of a condition that might interfere with the conduct or interpretation of the study.  
A complete list of exclusion criteria is provided in Section 7.2.  
In addition, subjects may not use any excluded medications, supplements, or food products. Concomitant 
medications and dietary products to be excluded are listed in Table 3. 
Main Criteria for Evaluation and Analyses: 
- Safety:  
Safety parameters will include AEs, clinical laboratory results, vital signs, physical examinations, electrocardiogram 
(ECG). AEs will be collected from signing the informed consent form (ICF) up until dosing on Day 1 as pretreatment 
events (PTEs), and any event that occurs from dosing until 14 days after the last dose will be captured as an AE. 
Vital signs will be recorded at Screening, Inpatient Check-in (Day -1), and throughout the dosing period. Vital signs 
will include tympanic body temperature measurement, blood pressure, respiration rate, and pulse (beats per minute 
[bpm]). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day 
-1) 15 minutes apart. Heart rate and blood pressure will be measured after at least 5 minutes supine and again at 2 
minutes after standing for all scheduled timepoints.  
Standard 12-lead ECGs will be recorded at Screening, Inpatient Check-in (Day -1), and periodically throughout the 
dosing period. Triplicate ECGs will be taken at each timepoint. 
A complete list of safety assessments is provided in Section 9.1, and the full Schedule of Study Procedures is 
provided in Appendix A. 
- PK:  
The plasma PK parameters are used as PK endpoints to determine drug exposure at each dose and facilitate dose 
escalations.  
Plasma samples will be collected for the determination of concentrations of CVN766 throughout the study as 
prescribed in the Schedule of Study Procedures (Appendix A). Cerebrospinal fluid (CSF) samples will be collected 
for the determination of concentrations of CVN766 as described in Section 9.6 and the Schedule of Study Procedures 
(Appendix A). PK sampling timepoints may be modified or added based on emerging PK data to most appropriately 
characterize the PK profile of CVN766 as determined by the SRG. 
PK parameters of CVN766 will be derived using noncompartmental analysis methods from the concentration-time 
data for all evaluable subjects. Actual sampling times, rather than scheduled sampling times, will be used in all 
computations involving sampling times. The following PK parameters will be determined from concentrations of 
CVN766 in plasma: Cmax, AUC from time 0 to the last quantifiable concentration (AUCt), AUC from time 0 to 
infinity (AUC∞), AUC from time 0 to 24 hours (AUC24), time to reach Cmax (tmax), terminal elimination rate constant 
(λz), terminal elimination half-life (t1/2z), apparent clearance (CL/F), and apparent volume of distribution (Vz/F). 
Multiple-dose PK will also include AUC over the dosing interval (AUCtau), apparent clearance at steady state 
(CL/Fss), apparent volume of distribution at steady state (Vz/Fss), steady-state nadir concentrations, and 
accumulation ratios  
The PK parameters to be determined from concentrations of CVN766 in CSF will include plasma: CSF ratio 
by time point. - Pharmacogenomics: 
One 6 mL whole blood sample will be collected at pre-dose on Day 1 for pharmacogenomic analysis; this will only 
be collected once per subject. Two 2.5 mL whole blood samples will be collected at pre-dose on Day 1 and at 
multiple timepoints post-dose for ribonucleic acid (RNA) pharmacogenomic analysis. The pre-dose RNA blood 
samples should be collected under fasted conditions and prior to any other blood collection. The samples will be 
stored for no longer than 15 years after completion of the CVN766 study and/or until the drug development of 
CVN766 is no longer actively pursued by Cerevance or its collaborators. No samples will be stored for longer than 
permitted by the applicable law, and samples will be destroyed upon notification from Cerevance. “Stored samples” 
in this context are defined as samples that are double coded (the samples are stripped of all personal identifying 


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CVN766 
 
Study No. CVN766-101 
Page 16 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRSD 
maximum recommended starting dose 
NCS 
not clinically significant 
NOAEL 
no-observed-adverse-effect-level 
Ox1R 
orexin 1 receptor 
Ox2R 
orexin 2 receptor 
PK 
pharmacokinetic 
PRL 
prolactin 
PT 
preferred term 
PTE 
pretreatment event 
QTcB 
QT interval with Bazett’s correction method 
QTcF 
QT interval with Fridericia’s correction method 
RNA 
ribonucleic acid 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAD 
single-ascending dose 
SAP 
statistical analysis plan 
SOC 
system organ class 
SRG 
Safety Review Group 
SUSARs 
suspected unexpected serious adverse reactions 
t1/2z 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to reach Cmax 
ULN 
upper limit of normal 
Vz/F 
apparent volume of distribution after extravascular administration 
Vz/Fss 
apparent volume of distribution after extravascular administration at steady state 
WHO 
World Health Organization 


CVN766 
 
Study No. CVN766-101 
Page 17 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
4.0 
INTRODUCTION 
4.1 
Background 
The neuropeptide orexin, also known as hypocretin, is produced exclusively in the orexigenic 
neurons in the hypothalamus. There are two forms of orexin, Orexin-A and orexin-B that are 
alternatively spliced from the same gene, HCRT.   There are two orexin receptors, orexin 1 receptor 
(Ox1R) and orexin 2 receptors (Ox2R), both of which are G-protein coupled receptors. Both 
orexin-A and orexin-B can bind to either receptor and in each case, agonist binding results in an 
increase in intracellular calcium levels. However, while orexin-A is equipotent at both receptors, 
orexin-B shows a 10-fold selectivity for Ox2R.  
Ox1R is selectively expressed in key brain areas relating to psychiatric disorders. Ox1R-expressing 
neurons in the bed nucleus of the stria terminalis, amygdala, locus coeruleus, raphe nucleus, and 
the ventral tegmental area are important in regulating emotions of stress, anxiety, motivation, and 
reward. CVN766 is a potent and highly selective small-molecule Ox1R antagonist with no 
significant off-target activity. Nonclinical PK and toxicology studies with CVN766 and other 
Ox1R antagonists have established their pharmacological characteristics and probable safety 
profile. 
Ox2R is expressed in some overlapping areas, including the raphe nucleus, ventral tegmental area, 
but also areas important to arousal and sleep regulation, including the tuberomammillary nucleus. 
The widely used sleep aid suvorexant (Belsomra®), approved for use in Australia, is a dual Ox1R 
and Ox2R antagonist, but its sleep-inducing effects are generally attributed to its activity on Ox2R. 
A second dual Ox1R and Ox2R antagonist, lemborexant, appeared safe and effective in clinical 
studies, has been approved in many countries worldwide, and has been submitted for marketing 
authorization in Australia.  
Clinical effects to be expected of a selective Ox1R antagonist remain uncertain. CVN766 has not 
yet been studied in humans. Other selective Ox1R antagonists have reported early-stage human 
clinical trials, notably JNJ-61393215 (ClinicalTrials.gov Identifier: NCT04080752; Salvadore et 
al., 2020) and ACT-539313 (NCT01954589; Kaufmann et al., 2020; Kaufmann et al., 2021). Both 
drugs were well tolerated and deemed safe for investigational use, the most common AEs being 
somnolence and mild headache.   
4.2 
Rationale for the Proposed Study 
CVN766 is a highly selective orexin-1 receptor (Ox1R) antagonist and may have utility as 
treatment for psychiatric disorders including schizophrenia, panic disorder and anxiety, and 
addiction. Its safety and PK profile have been preliminarily established in nonclinical toxicology 
studies. The present study will be the first conducted in humans with CVN766 and will examine 
the compound's safety, tolerability, and PK in healthy subjects. 
Nonclinical pharmacology, toxicity, and pharmacokinetic (PK) studies support the proposed 
escalating single- and multiple-dose study of CVN766 in healthy subjects with a starting dose of 
5 mg. Section 6.2 outlines the justification for the planned dose ranges.  
 


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CVN766 
 
Study No. CVN766-101 
Page 20 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
6.0 
STUDY DESIGN AND DESCRIPTION 
6.1 
Study Design 
This is a phase 1, randomized, double-blind, placebo-controlled, single- and multi-dose ascending 
study in healthy subjects. Figure 1 provides a schematic illustration of the study. 
Figure 1 
CVN766-101 Study Schematic 
 
 
6.1.1 Part 1: Single-Dose Regimen and Fasted-Fed Crossover 
Approximately 40 subjects will be enrolled in 1 of the 5 single-dose cohorts (designated as S1 
through S5, respectively) in an ascending fashion. Dose escalation will only occur after a fully 
blinded review of all available safety, tolerability, clinical laboratory results (minimally including 
samples collected from subjects through 72-hours post-dose), and available PK data, including at 
least a 72-hour follow-up of the most recent cohort. 


CVN766 
 
Study No. CVN766-101 
Page 21 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
The planned dose levels are provided in Table 5. Each cohort will consist of 8 subjects randomized 
to CVN766 or placebo, whereby 6 subjects will receive a single dose of CVN766 and 2 subjects 
will receive a matching placebo under overnight fasted conditions.  
Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in 
each cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 
to the remainder of subjects within the cohort. After blinded review of 24-hour post-dose safety 
and tolerability data, the remaining 6 subjects of each cohort may be dosed provided that the 
adverse event (AE) profile of CVN766 in the first 2 subjects is considered acceptable.  
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the 
unit for safety and PK assessments at least 72 hours after dosing. On Day 1, subjects will undergo 
safety monitoring (including labs, physical exam, abbreviated neuro exam, cardia telemetry at 12-
hours pre-dose) and PK sampling from blood plasma through 72 hours post-dose.  In addition, for 
cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. For subjects 
participating in the SAD cohorts, the total confinement period will be 4 nights unless extended for 
management of AEs at the discretion of the Investigator. Follow-up assessments will occur on 
approximately Days 8 and 14. 
To assess the effect of food on bioavailability of CVN766 in suspension formulation, single-dose 
administration will be repeated in a single cohort after ingestion of a standardized high-fat high-
calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed 
bioequivalence studies, Dec 2002). Once the safety of the S3 cohort dose level has been assessed, 
the S3 cohort subjects will return to the clinic (no sooner than 14 days after their prior dose, or at 
least 4 half-lives has lapsed based on preliminary PK data, whichever is longer) and will receive 
the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish 
the entire content of their breakfast within 25 minutes and will receive an investigational product 
30 minutes (± 5 minutes) after beginning the meal. Sentinel dosing will not be required for subjects 
returning to the clinic for the fed regimen.  If the CVN766 PK parameters in the fasted S3 cohort 
reveal poor absorption with inconclusive results, the fed cohort will be deferred until a higher dose 
level. 
An outline of the single-dose study visit schedule is included in Table 1. A Schedule of Study 
Procedures is listed in Appendix A. 
Table 1 
Single-Dose Visit Schedule 
Screening a 
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b 
Inpatient PK 
& 
Safety 
Assessments 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
Day -28 to -2 Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14  
±2 days 
(a) Screening will occur at study entry. Subjects returning for the “Fed” repetition of the single-dose regimen 
will not undergo Screening assessments except as required at Day -1. 
(b) CSF collection will apply only to cohort S3 (fasted). 
(c) Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs. 
(d) The final follow-up assessment will occur by telephone unless abnormal CS findings are observed upon 
discharge. In these cases, subjects must return to the clinic for re-evaluation. 


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6.1.2 Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 subjects will be enrolled in 1 of the 3 multiple-
dose cohorts (designated as M1 through M3, respectively) in an ascending fashion.  Dosing will 
be administered in the fasting state; this can be changed by the SRG if exposure is found to be 
higher in the fed state. The dose levels planned to be studied in the multiple-dose regimen (M1 
through M3) are provided in Table 5. Each multiple-dose cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a daily dose of CVN766, and 
2 subjects will receive matching placebo for 7 days. However, the duration may be increased to 
≤14 days at the discretion of the safety review group (SRG) if preliminary PK data suggest steady-
state will not be achieved within 6 days of daily dosing. Unlike the single-dose regimen, sentinel 
dosing within cohorts is not required in the multiple-dose regimen. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and 
remain in the unit for the duration of the dosing period and for at least 48 hours after the last dose 
for safety and PK assessments before discharge. On treatment Days 1 and 7, subjects will undergo 
safety monitoring and PK sampling from blood plasma through 48 hours post-dose and, in cohort 
M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, on treatment Day 7 (or 
last day of dosing, if extended beyond Day 7), subjects will additionally undergo PK sampling 
from CSF via lumbar puncture at 3 hours post-dose. If needed to resolve questions arising from 
prior cohorts’ data, subjects in cohort M3 also may, at SRG discretion, undergo PK sampling from 
CSF via lumbar puncture, the choice of day (e.g., Day 1 or Day 7) and sampling time to be decided 
by SRG. Subjects in MAD cohorts may be asked to return to the clinic for an additional plasma 
PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK data, i.e., t½. The 
total confinement period will be 9 nights unless extended for additional dosing days or for 
management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final 
dose. A summary of multiple-dose study visits is included in Appendix A.  
Table 2 
Multiple Dose Visit Schedule 
Screening 
Inpatient  
Check-in 
Dosing, 
PK, 
CSF, & Safety 
Assessments  a,f 
PK 
/ 
Safety 
Assessments 
& 
inpatient discharge b 
Follow-Up 
Outpatient 
Visits c 
Follow-Up Call d 
Day -28 to -2 Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g. Days 
8-9) 
3 days ±0 after last dose 
(e.g. Day 10) &  
7 days ± 1 after last dose 
(e.g. Day 14) 
14 days ±2 after 
last 
dose 
(e.g. 
Day 21) 
(a) CSF sampling will occur on Day 7 in cohorts M1 and M2. Cohort M3 also may, at SRG discretion, undergo 
PK sampling from CSF, the choice of day and sampling time to be decided by SRG. 
(b) Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or if necessary, 
to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after the last dose (e.g., 
Day 10) may be omitted at Investigator’s discretion. 
(d) The Follow-up Visit will occur by telephone unless abnormal CS findings are observed upon discharge. In 
these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to ≤14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in cohort M1. 


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6.1.3 Dose Escalation  
The SRG will be comprised of the Investigator, Medical Monitor, Cerevance Responsible Medical 
Officer and may include other Cerevance representatives. A pharmacokineticist and other subject 
matter experts may participate as needed. The SRG will be responsible for ongoing review of 
safety, tolerability, clinical laboratory results, and available PK data and deciding to: 
• Expand each single-dose cohort from the sentinel cohort to the full cohort (based on a 
review of at least 24 hours post-dose safety data from each of the sentinel subjects), 
• Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in single-dose cohorts (based on a review of available data including at least 72 
hours post-dose safety data and clinical laboratory results from each of the subjects in the 
current cohort),  
• Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in multiple-dose cohorts (based on a review of available data including at least 48 
hours post 7th dose safety data from each of the subjects in the current cohort), 
• Add additional dose cohort(s) in either the single- or multiple-dose studies, 
• Increase the duration of dosing in the multiple-dose cohorts from 7 days to ≤14 days 
If 2 or more subjects in a single cohort experience the same type of serious or medically adverse 
event, further dosing will be withheld until the SRG investigates the events.  Based on this 
assessment, the SRG will determine if the study should be terminated or continued and whether 
modification of planned dose levels and/or implementation of additional safety monitoring is 
indicated.   
For each cohort (including sentinel subjects, where applicable), the SRG will carefully review the 
available blinded safety, tolerability, clinical laboratory results, and PK data to determine whether 
dosing should stop or continue (and, if continued, at what dose, including whether to repeat the 
previous dose), whether additional sequential dosing should be implemented in future cohorts or 
whether the blind should be broken to identify whether the subjects received CVN766 or placebo. 
However, precautions must be taken not to unblind the study staff, including the investigator. 
If all doses are tolerated, then additional cohorts with higher doses may be considered; if MTD is 
reached in an earlier cohort, following cohorts may study lower doses. The actual choice of the 
subsequent dose level will occur after the full review of the available blinded safety, tolerability, 
clinical laboratory results, and available PK data in the preceding cohort. The subsequent dose 
level may be higher, lower, or remain the same as the preceding dose level. If necessary, additional 
cohort(s) may be added to fully characterize the safety and tolerability of CVN766. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all available 
safety, tolerability, and clinical laboratory results for the fasting drug administration to single-dose 
Cohort S3 (minimally including samples collected through Day 4) and available PK data. For each 
multiple-dose cohort after the first, the actual choice of dose level may be modified by the SRG 
after review of the available blinded safety, tolerability, and clinical laboratory results and PK data 
in the preceding multiple-dose and next-higher-dosage single-dose cohorts (i.e., multiple-dose 
Cohort M2 will not initiate until the data review for multiple-dose Cohort M1 and single-dose 


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cohort S4 is complete). Each subsequent dose level may be higher, lower, or remain the same as 
the preceding dose level. 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully 
characterize the safety and tolerability of CVN766. Such additional cohorts will follow the same 
schedule of events as for prior multiple-dose cohorts. Additional/Alternative PK timepoints may 
be implemented if the SRG determines this is necessary to fully characterize the PK profile of 
CVN766. 
All AEs reported during the Treatment Period, both within and across cohorts, up to the time of 
discharge, will be evaluated to assess the need for the subject and/or study termination in 
accordance with the prespecified criteria for discontinuation/termination (Section 6.3.1).  
Additionally, the SRG may decide not to escalate the dose for a particular cohort but rather 
administer the same or a lower dose level to the next cohort. Additional/ Alternative PK timepoints 
may be implemented if the SRG determines this is necessary to fully characterize the PK profile 
of CVN766. 
6.2 
Justification for Study Design, Dose, and Endpoints 
The study is double-blind and placebo-controlled to avoid subjective bias in the assessment of the 
safety and tolerability of CVN766. Dose escalation will be predicated on a review of available 
blinded safety, tolerability, and PK data observations for each prior dose cohort.  
The sponsor has selected the starting dose level considering the FDA Guidance for Industry 
(Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult 
Healthy Volunteers, 06 July 2005) and providing additional safety factors to the initial calculations 
based on the principles outlined in the guidance. The toxicity profile of CVN766 after oral dosing 
was examined in repeat dosing studies in rats and dogs. Scaling based on body surface area was 
conducted by multiplying the NOAELs for the most sensitive animal species by the appropriate 
conversion factors. Based on these calculations and applying a 10-fold safety margin below the 
NOAEL human-equivalent dose (HED), the maximum recommended starting dose (MRSD) for 
this first-in-human study is 167 mg for a 60 kg subject. The selected starting dose level is 5 mg. 
The study's multiple-ascending dose (MAD) portion seeks to prepare for subsequent repeat dosing 
studies in subjects. Each MAD dose level will have been studied or exceeded in the SAD portion 
of the study before its use in a MAD cohort.  
Nonclinical toxicity study data provide a basis for calculating the maximum exposure level that 
can be presumed safe. Escalating to the HED of the NOAEL in the most sensitive animal species, 
the maximum dose for clinical use is 1670 mg/day.  
The projected t1/2z in animal species ranged up to 6.5 hours, so sample collection through Inpatient 
Discharge 72 hours post-dose is expected to correspond to more than 5 half-lives and is anticipated 
to be adequate to document elimination of CVN766. The study design allows for collecting 
additional PK samples at later timepoints if preliminary emerging PK results are indicated.  
AEs, physical exams, vital signs, ECG findings, and clinical laboratory results are used as safety 
assessments to determine dose tolerability and dose-limiting effects of CVN766. The plasma PK 
and CSF parameters and PK endpoints will help elucidate the pharmacology of CVN766.  


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Samples for DNA analysis will be collected and may be used to evaluate drug metabolic enzyme 
and transporter polymorphisms that may contribute to the variability in the PK of CVN766. 
6.3 
Premature Termination or Suspension of Study or Investigational Site 
6.3.1 Criteria for Premature Termination or Suspension of the Study 
The study will be completed as planned unless new information or other evaluation regarding the 
safety of the study medication indicates an adverse change in the risk profile for the compound, 
such that the SRG or Institutional Review Board (IRB) considers the risk is no longer acceptable 
for subjects participating in the study. 
In addition, if any of the following occur, further dosing will be withheld until the SRG reviews 
the relevant data, including unblinded data (if deemed necessary by the SRG request), and will 
decide whether it is safe to suspend dosing or continue dosing at either the planned or alternative 
dose levels or decides to prematurely terminate the study: 
1. Two or more subjects in any single cohort or across more than 1 cohort experience the same 
type of serious or Medically Significant event as defined by the Investigator 
2. Two or more subjects in any single cohort or across more than 1 cohort experience alanine 
aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations >5 × upper limits 
of normal (ULN) in the absence of a concomitant bilirubin increase (see point 3 below) 
3. One or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN in the presence of a total bilirubin increase >2 ×ULN or an 
international normalized ratio (INR) >1.5 without findings of cholestasis or other alternate 
etiology to explain the elevations (i.e., “Hy’s Law cases”) 
4. Two or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
6.3.2 Criteria for Premature Termination or Suspension of Investigational 
Sites 
A study site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant violation of Good Clinical Practice (GCP), protocol, or contractual agreement, 
is unable to ensure adequate study performance, or as otherwise permitted by the contractual 
agreement. 
6.3.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s) 
In the event that the sponsor, an IRB/independent ethics committee (IEC), or regulatory authority 
elects to terminate or suspend the study or the participation of an investigational site, a study-
specific procedure for early termination or suspension will be provided by the sponsor; applicable 
investigational sites will follow the procedure during the course of termination or study 
suspension. 


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7.0 
SUBJECT POPULATION 
Screening for eligible subjects will be performed within 28 days prior to randomization or first 
dose.  
7.1 
Inclusion Criteria 
Subject eligibility is determined according to the following criteria prior to entry into the study: 
1. In the investigator's opinion, the subject can understand and sign the Informed Consent Form 
and comply with all protocol requirements.  
2. The subject is a healthy male or female adult who is 18 to 55 years of age, inclusive at the time 
of ICF. 
3. Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 32.0 kg/m2, inclusive 
at Screening.  
4. A male subject who is nonsterilized* and sexually active with a female partner of childbearing 
potential* agree to use two forms of adequate contraception* from signing the ICF throughout 
the study and for 90 days after the last dose. 
*Definitions and acceptable methods of contraception are defined in 
Section 9.1.13 Contraception and Pregnancy Avoidance Procedure, and 
reporting responsibilities are defined in Section 9.1.14 Pregnancy. 
5. A female subject of childbearing potential who complies with contraception requirements* or 
a female with no childbearing potential, defined as the subject has been surgically sterilized 
(hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (defined 
as continuous amenorrhea of at least 2 years and FSH>40 IU/L). 
7.2 
Exclusion Criteria 
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. Subject has received any investigational compound within 30 days prior to the first dose of 
study medication or within 5 half-lives, whichever is greater. 
2. Subject is a study site employee or an immediate family member of a study site employee.  
3. Subject has evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic 
disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious 
allergy, full-body allergic skin rash (including hives), psychiatric disorder, evidence of 
abnormal liver function test, evidence of abnormal renal function tests or other abnormality 
that may impact the ability of the subject to participate or potentially confound the study 
results.  
Note: Healthy volunteers with pre-existing stable disease, defined as diseases not requiring 
significant change in therapy or hospitalization for worsening disease during the 6 wks before 
enrolment, may be included at the discretion of the Investigator. 
4. There is any finding in the subject’s medical history, physical examination, or safety laboratory 
tests giving reasonable suspicion of a disease that would contraindicate taking CVN766 or a 
similar drug in the same class or that might interfere with the conduct of the study 


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5. Subject has a known hypersensitivity to any component of the formulation of CVN766. 
6. Subject has a positive urine result for drugs of abuse at Screening or Inpatient Check-in (Day -
1). 
7. Subject has a history of a major psychiatric illness or currently receiving therapy for a 
psychiatric condition 
8. Subject has a history of drug abuse or a history of alcohol abuse (more than 14 units/week) 
within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and 
drugs throughout the study. 
9. Subject has taken any excluded medication, supplements, or food products listed in the 
Excluded Medications and Dietary Products table as listed in Table 3: Excluded Medications 
and Dietary Products. 
10. Male subjects who do not agree to all the following rules: when sexually active with a female 
partner(s) of childbearing potential during the study, and for 90 days after the last dose of study 
drug: a) must use two acceptable methods of birth control (condom or surgical sterilization 
combined with highly effective method of contraception for the female partner) and b) refrain 
from sexual activity with female partners who do not use an acceptable method of birth control. 
Barrier contraception (condom) must be used by all-male subjects who were not surgically 
sterilized at least 90 days prior to screening. Male subjects must also agree to refrain from 
sperm donation during the study and until 90 days after the last dose of the study drug. 
11. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova 
during the study or 30 days after the last dose of the study drug. Women of childbearing 
potential must agree to practice an acceptable method of birth control (e.g., oral or parenteral 
contraceptives, intrauterine device, barrier, abstinence).  
*Definitions and acceptable methods of contraception are defined in Section 9.1.13. 
Contraception and Pregnancy Avoidance Procedure and reporting responsibilities are 
defined in Section 9.1.14 Pregnancy. 
12. Subject has previously had a seizure or convulsion (lifetime, with the exception of febrile 
seizures), including absence seizure. 
13. Subject has current o recent (within 6 months) gastrointestinal disease that would be expected 
to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention 
known to impact absorption [e.g., bariatric surgery or bowel resection], esophageal reflux, 
peptic ulcer disease, erosive esophagitis, or frequent [i.e., more than once per week] occurrence 
of heartburn). 
14. Subject has a history of cancer or other malignancy, except for basal cell carcinoma or 
squamous cell carcinoma that has been in remission for at least 3 years prior to Day 1. 
15. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody, or a human immunodeficiency virus infection at Screening. 
16. Subject who regularly use nicotine-containing products (including but not limited to cigarettes, 
electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). The 


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casual users may participate but must agree to refrain from the time of Screening for the 
duration of the study or a positive urine cotinine test at Inpatient Check-in (Day 1). 
17. Subject has poor peripheral venous access (defined as more than three failed attempts to 
cannulate. 
18. Subject has donated or lost 450 mL or more of their blood volume (including plasmapheresis) 
or had a transfusion of any blood product within 45 days prior to Day 1. 
19. Subject has an abnormal (CS) ECG at Screening or Inpatient Check-in (Day -1). Entry of any 
subject with an abnormal (NCS) ECG must be approved and documented by signature by the 
Investigator or medically qualified sub-investigator.  
20. Subject has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 
40 to 90 mm Hg for diastolic, confirmed with repeat per PI discretion, at the Screening Visit 
or Inpatient Check-in (Day -1). 
21. Subject has a resting heart rate outside the range of 40 to 100 bpm, confirmed with repeat per 
PI discretion, at the Screening Visit or Inpatient Check-in (Day -1). 
22. Subject has a QT interval with Fridericia’s correction method (QTcF) >450 ms (males) or 
>470 ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat testing 
at the Screening Visit or Inpatient Check-in (Day -1) Visit. 
23. Subject has abnormal Screening or Inpatient Check-in (Day -1) laboratory values that suggest 
a CS underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 
the ULN, confirmed with one repeat testing. 
24. Subject has a risk of suicide according to the investigator’s clinical judgment or has made a 
suicide attempt in the previous 2 years. 
7.3 
Excluded Medications and Dietary Products 
Use of the agents in Table 3 (prescription or nonprescription) is prohibited from the time points 
specified until completion of all study activities. 
Table 3 
Prohibited Medications and Dietary Products 
28 days prior to Inpatient Check-in  
(Day -1) 
7 days prior to Inpatient Check-in  
(Day -1) 
72 hours prior to Inpatient 
Check-in  
(Day -1) 
Prescription medications (including 
oral contraceptives) 
OTC 
medications, 
including 
antacids, proton-pump inhibitors, 
and H2 receptor antagonists (a) 
Products containing caffeine or 
xanthine (e.g., tea or coffee) 
Nicotine-containing products 
Vitamin supplements 
poppy seeds 
Nutraceuticals (e.g., St. John’s wort, 
ginseng, kava kava, ginkgo biloba, 
Chinese herbs, and melatonin) 
Orexin 
receptor 
antagonists 
including suvorexant (Belsomra®), 
lemborexant (Dayvigo®), and related 
compounds 
 
Immunization/Vaccines (b) 
Alcohol-containing products 
 
Known strong inhibitors/inducers of 
CYPs 3A4/5 (c) 
 
 
CYP= cytochrome P-450, OTC=over the counter. 


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(a) Occasional use of acetaminophen (~1 g/day) and 400mg ibuprofen TDS when required or other medication as 
approved by the sponsor’s Medical Monitor on a case-by-case basis is allowed except on Day 1 
(b) Inclusive of but not limited to H1N1 and flu vaccinations. Subjects who have received the COVID19 Vaccine 
between -10 and -28 days may participate provided they did not experience any side effects of any description. 
COVID vaccine doses may be administered 7 days post-study medication dosing.  
(c) e.g., chloramphenicol, clarithromycin, ketoconazole. 
Subjects must be instructed not to take any medications during study participation, including over-the-counter drug 
products, without first consulting with the investigator. 
7.4 
Diet, Fluid, Activity Control  
Subjects will be confined to the clinic for each of the dosing days as well as a period of time 
sufficient to collect additional post-dose PK samples and monitor for safety and tolerability (Day 
-1 through Day 4 for single-dose cohorts and Day-1 through Day 9 for multiple-dose cohorts). 
During confinement, subjects will be provided 3 standard meals and a snack per day, each 
containing approximately 30% fat (relative to the total calories). The meals served on the day of 
dosing should be similar in nutritional content for each subject in the study. The study menu should 
be recorded and submitted to the study file with a copy provided to the sponsor prior to the start 
of the study. Breakfast will not be provided on dosing days until at least 1 hour after dose 
administration unless otherwise indicated (i.e., Days 2-6 for MAD cohorts). The meal start and 
stop times and percentage of the meal consumed will be recorded in the source and appropriate 
electronic case report form (eCRF) for all meals served on dosing days.  
If a blood draw or any study procedure coincides with a meal, the blood draw will take precedence, 
followed by the study procedure and then the meal. 
Subjects will remain in bed at a semi-supine position for 4 hours following the dose administration, 
except as necessitated by the occurrence of an AE or study procedures (e.g., obtaining a 12-lead 
ECG). Subjects must refrain from strenuous exercise from 72 hours before Inpatient Check-in and 
until check-out. 
On the dosing days where extensive PK and/or CSF sampling is indicated (i.e., single-dosing Day 
1 and first and last multiple-dose days, e.g., days 1 and 7), CVN766 or placebo suspension will be 
administered with approximately 240 mL of water after a fast of at least 10 hours. Subjects will 
continue to fast for an additional 4 hours after dosing and eat lunch following the 4-hour PK blood 
and CSF collection. Subjects may consume water ad libitum except for 1 hour before and 1 hour 
after drug administration. 
For the food effect cohort (S3), single-dose administration will be administered after ingesting a 
standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect 
bioavailability and fed bioequivalence studies, Dec 2002). Subjects will finish the entire content 
of their breakfast within 25 minutes and will receive an investigational product 30 minutes (±5 
minutes) after beginning the meal. The S3 (food effect) cohort meals may be staggered to ensure 
dosing occurs 30 minutes after the beginning of the meal. 
Subjects will also fast for at least 10 hours prior to safety laboratory collection times as indicated. 
However, consumption of water as desired is permitted during this time, except for dosing days, 
as indicated above. 


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7.5 
Criteria for Discontinuation or Withdrawal of a Subject 
The primary reason for discontinuation or withdrawal of the subject from the study or study 
medication should be recorded in the eCRF using the following categories. For screen failure 
subjects, Section 9.1.15. 
1. The subject has experienced a PTE or AE that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health or the subject is unwilling to 
continue because of the PTE or AE. 
2. Liver Function Test (LFT) Abnormalities 
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests, until a subject’s laboratory profile has returned to 
normal/baseline status) if the following circumstances occur at any time during study 
medication treatment: 
– ALT or AST >8 × ULN, or 
– ALT or AST >5 × ULN and persists for more than 2 weeks, or 
– ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or INR >1.5, 
or 
– ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
3. Significant protocol deviation. The discovery post-randomization that the subject failed to 
meet protocol entry criteria or did not adhere to protocol requirements and continued 
participation poses an unacceptable risk to the subject’s health. 
4. Lost to follow-up. The subject did not return to the clinic and attempts to contact the subject 
were unsuccessful. Attempts to reach the subject must be documented. 
5. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF. 
Note: All attempts should be made to determine the underlying reason for the withdrawal, and, 
where possible, the primary underlying reason should be recorded (i.e., withdrawal due to an 
AE). 
6. The sponsor, IRB, IEC, or regulatory agency terminates the study. 
7. Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
7.6 
Procedures for Discontinuation or Withdrawal of a Subject 
The investigator must discontinue a subject’s study participation at any time during the study when 
the subject meets the study discontinuation criteria described in Section 7.5. In addition, a subject 
may discontinue his or her participation without giving a reason at any time during the study. 
Should a subject’s involvement be terminated, the primary criterion for termination must be 
recorded by the Investigator. In addition, efforts should be made to perform all procedures 


CVN766 
 
Study No. CVN766-101 
Page 31 of 81
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CONFIDENTIAL 
scheduled for the Early Termination Visit. Discontinued or withdrawn subjects may be replaced 
at the  Sponsor’s discretion. 
Participants who withdraw from the study prior to dosing may be replaced. If a participant 
withdraws after the first dose of study medication or placebo, no replacement will occur. 


CVN766 
 
Study No. CVN766-101 
Page 32 of 81
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CONFIDENTIAL 
8.0 
CLINICAL TRIAL MANAGEMENT 
8.1 
Study Medication and Materials 
This section contains information regarding all medication and materials provided directly by the 
sponsor and/or sourced by other means required by the study protocol, including important 
sections describing the management of clinical trial material. 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling 
Study drug refers to CVN766 and matching placebo. Study drug will be provided in bulk supply. 
An unblinded pharmacist will manage and prepare doses as oral suspensions as needed throughout 
the study.  
In this protocol, the term study medication refers to all or any of the drugs defined below. 
8.1.1.1 Investigational Drug 
CVN766 and Matching Placebo 
CVN766 drug substance is supplied as a bulk powder to the clinical site and then compounded 
into oral suspensions. A matching placebo suspension containing all of the components of the 
active oral suspension with the exception of the drug substance will also be compounded by the 
site. Compounding instructions will be outlined in a separate pharmacy manual and provided by 
the sponsor. See Table 4 for the composition of the drug product and matching placebo 
suspensions.  
The oral suspensions will be labeled with the appropriate study information and caution 
statements.  
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo 
Component 
CVN766 Oral Suspension (individual dose) 
Matching 
Placebo 
CVN766 drug substance 
5 mg 
15 mg 
45 mg 
125 mg 
250 mg 
NA 
 Commercial suspending vehiclea 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
NA=Not applicable;  
a An off-the-shelf commercial suspending vehicle will be used, and the details of the vehicle will be provided in the 
Pharmacy Manual. 
 
8.1.1.2 Ancillary Materials  
Ancillary materials will be provided by either the clinical site and/or the sponsor based on 
availability.  
Ancillary material details are provided in the pharmacy manual. 


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CVN766 
 
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CONFIDENTIAL 
 
Table 5 
Planned Single and Multiple Dose Levels by Cohort 
Single-Dose Cohorts 
 
 
 
Cohort 
Planned Treatment* 
No. of Subjects 
Medication Type 
S1  
CVN766 5 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S2 
CVN766 15 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S3 Fasted 
CVN766 45 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S3 Fed (Same 8 subjects as 
in the S3 FASTED cohort) 
CVN766 45 mg 
6 
oral suspension 
 
Placebo 
2 
oral suspension 
S4 
CVN766 125 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S5 
CVN766 250 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
Multiple Dose Cohorts 
Cohort 
Planned Treatment* 
No. of Subjects 
Medication Type 
M1  
CVN766 45 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
M2  
CVN766 125 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
M3 
CVN766 250 mg 
6 
oral suspension 
 
Placebo 
2 
oral suspension 
* Dose (active or placebo) is in 10 mL of suspension. 
8.1.4 Overdose 
An overdose is defined as a known, deliberate, or accidental administration of an investigational 
drug, to or by a study subject, at a dose above that assigned to that individual subject according to 
the study protocol. 
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF, in order to capture this important safety information consistently in the database. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE eCRF(s) according to Section 9.7.2, PTEs and AEs. 
Serious adverse events (SAEs) associated with an overdose should be reported according to the 
procedure outlined in Section 9.7.4, Collection and Reporting of SAEs. 
In the event of an overdose, supportive measures should be employed as needed, e.g., 
administration of supportive therapy as dictated by the subject’s clinical status, removal of 
unabsorbed material from the gastrointestinal tract, or initiation of additional clinical monitoring.  


CVN766 
 
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8.2 
Investigational Drug Assignment and Dispensing Procedures 
Subjects will be assigned to receive a unique randomization number.  
The clinical site will use the unique identifier to facilitate the pre-labeling of PK samples. It should 
also be contained on the PK transport vials shipped to the bioanalytical laboratory and will be used 
by the laboratory to report the subject data results. This unique identifier should only be used for 
the purposes described in this section. This identifier will be assigned upon randomization in the 
order in which subjects receive their first dose of the study drug.   
8.3 
Randomization Code Creation and Storage  
The sponsor or their designee will generate the randomization schedule and provide a copy to the 
site pharmacist and bioanalytical laboratory prior to the start of the study. All randomization 
information will be stored in a secured area, accessible only by authorized personnel.  
8.4 
Investigational Drug Blind Maintenance 
The investigational drug blind is maintained through a randomization schedule held by the 
dispensing pharmacist. 
8.5 
Unblinding Procedure 
The investigational drug blind shall not be broken by the investigative staff unless information 
concerning the investigational drug is necessary for the medical treatment of the subject. All study 
assessments and causality assessments should be performed, if possible, prior to unblinding. In the 
event of a medical emergency, if possible, the medical monitor should be contacted to discuss the 
need for unblinding before the investigational drug blind is broken. 
Unblinding envelopes will be supplied to the site prior to the first subject dosing and stored in a 
central and secure place to ensure access in the event of an emergency.  Study staff will be trained 
on unblinding procedures. 
The sponsor must be notified as soon as possible if the investigational drug blind is broken. The 
date, time, and reason the blind is broken must be recorded in the source documents, and the same 
information (except the time) must be recorded on the eCRF. 
If any site personnel inadvertently become unblinded, the sponsor must be notified, and the SRG 
will determine whether to discontinue dosing or withdraw from the study of all affected subjects. 
No change should be made to any assessment of the subject after unblinding. 
Following assessment of the AE data and pre-defined criteria for study termination, dose escalation 
may be interrupted/stopped and the blind broken for further analysis. Based on a review of 
unblinded data, the sponsor, in consultation with the Investigator, will decide if and how it is 
appropriate for the study to proceed. 
The Randomization schedule for all subjects will be released for analysis after the database for 
these cohorts is locked. The Investigator will be unblinded after database lock for all the cohorts 
if necessary. 


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8.6 
Accountability and Destruction of Sponsor-Supplied Drugs 
Drug supplies will be counted and reconciled at the site before being returned to the sponsor or 
designee or being destroyed.  
The investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to subjects enrolled in the study. To document appropriate 
use of study medication, the investigator must maintain records of all study medication delivery to 
the site, site inventory used by each subject, and return to the sponsor or designee. 
Upon receipt of study medication, the investigator or designee must verify the contents of the 
shipments against the packing list, ensure the quantity is correct, and the medication is received 
within the labeled storage conditions. If quantity and conditions are acceptable, the investigator or 
designee should acknowledge the receipt of the shipment by signing the bottom half of the packing 
list and send via email and per instructions provided on the form. If any discrepancies exist 
between the packing list and the actual product received, the sponsor must be contacted to resolve 
the issue. The packing list should be filed in the investigator’s essential document file. The 
investigator must maintain 100% accountability for all study medication received and dispensed 
during their entire participation in the study. Proper drug accountability includes, but is not limited 
to: 
• Continuously monitoring expiration dates 
• Frequently verifying that actual inventory matches documented inventory 
• Verifying that the log is completed for the drug lot used to prepare each dose 
• Verifying that all containers used are documented accurately on the log 
• Verifying that required fields are completed accurately and legibly 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
The investigator or designee must record the current inventory of all study medication on a 
sponsor-approved drug accountability log. The following information will be recorded at a 
minimum: protocol number and title, name of the Investigator, site identifier and number, 
description of study medication, expiry date, and amount dispensed, including the initials of the 
person dispensing and receiving the study medication. The log should include all required 
information as a separate entry for each subject to whom study medication is dispensed. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform clinical study material accountability and reconciliation before clinical study 
materials are returned to the sponsor or its designee for destruction or destroyed at the site, as 
applicable. The investigator will retain the original documentation regarding clinical study 
material accountability, return, and/or destruction, and copies will be sent to the sponsor or 
designee. 
The investigator will be notified of any expiry date or retest date extension of clinical study 
material during the study conduct. On expiry date notification from the sponsor or designee, the 
site must complete all instructions outlined in the notification, including segregation of expired 
clinical study material for return to the sponsor or its designee for destruction. 


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9.0 
STUDY PLAN 
9.1 
Study Procedures 
The following sections describe the study procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel whenever possible. The 
Schedule of Study Procedures is located in Appendix A. 
9.1.1 Informed Consent Procedure 
The requirements of the ICF are described in Section 14.2. 
The ICF must be obtained prior to the subject entering the study and before any protocol-related 
procedures are performed. 
A unique subject screening number (of the form xx-xxx), the first two numbers for the site, 
subsequent three numbers for subject identification will be assigned to each subject when the ICF 
is obtained. This subject ID will be used until the subject is assigned their 4-digit randomization 
number. 
9.1.1.1 Pharmacogenomic and Cerebrospinal Fluid Informed Consent Procedure 
Pharmacogenomics and cerebrospinal fluid informed consent is a component of the overall study 
ICF. The requirements are described in Section 14.2. 
The pharmacogenomic and (for applicable cohorts) cerebrospinal fluid sample collection is 
mandatory. 
9.1.2 Demographics, Medical History, and Medication History Procedure 
Demographic information to be obtained will include date of birth, sex, ethnicity, race as described 
by the subject, smoking status, and caffeine consumption at Screening. 
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases that stopped at or prior to signing the ICF. Ongoing conditions are 
considered concurrent medical conditions (see Section 9.1.7). 
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days before signing ICF. 
9.1.3 Physical Examination Procedure 
A physical examination performed by the investigator or medical officer consist of the following 
body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; 
(5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; 
(9) nervous system; (10) lymph nodes; (11) abbreviated neurological exam; and (12) other.  
Any abnormal change from the baseline physical examination (Screening and Inpatient Check-in 
[Day -1]) must be assessed as not CS or CS by the investigator and recorded in the source document 
and eCRF.  


CVN766 
 
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All CS findings/changes, as determined by the investigator, from the baseline physical 
examination will be recorded as a PTE or concurrent medical condition in the source document 
and on the appropriate eCRF described in Section 9.8.1 or Section 9.8.2.  
On subsequent examinations, any abnormal change from the pretreatment physical examination 
assessment occurring immediately prior to the start of the investigational drug Inpatient Check-in 
(Day -1) must be assessed as not clinically significant (NCS) or CS by the investigator and 
recorded in the source document and eCRF. Any CS change or new diagnosis as a result of a CS 
change, as determined by the investigator, will be recorded as an AE in source documentation and 
on the PTE/AE eCRF. 
9.1.4 Weight, Height, and BMI 
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below:  
Height is recorded centimeters without decimal places, and for weight, it is kilograms (kg) with 1 
decimal place. BMI should be derived as: 
Metric:  
BMI = weight (kg)/[height (m)]2 
Results for BMI will be expressed with 1 decimal place. 
Example: 
Height=176 cm (or 1.76 m), weight=79.2 kg; BMI=79.2/1.762=25.57 kg/m2 captured as 
25.6 kg/m2.  
9.1.5 Vital Sign Procedure 
Vital signs will include tympanic body temperature, respiration, pulse, and blood pressure and be 
collected at timepoints specified in the Schedule of Study Procedures (Appendix A). For eligibility 
determination, the pulse will not be derived from ECG. Pulse and blood pressure will be measured 
after at least 5 minutes supine and again after 2 minutes standing.  
Vital signs should be measured at the same time (+/- 1 hour) of the day across visits if possible. 
When vital signs are scheduled at the same time as blood draws, the blood draw will take priority, 
and vital signs will be obtained within approximately 0.25 hours before or after the scheduled 
blood draw. 
9.1.6 Documentation of Concomitant Medications 
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by the sponsor. At each study visit, subjects will be asked whether they have taken 
any medication other than the study medication (used from signing of ICF through the end of the 
study), and all medication, including vitamin supplements, over-the-counter medications, and oral 
herbal preparations, must be recorded in the eCRF. Documentation will include generic medication 
name, dose, unit, frequency, route of administration, start and end dates, and reason for use. 


CVN766 
 
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9.1.7 Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at the signing of ICF. This includes CS laboratory, ECG, or physical examination abnormalities 
noted at Screening examination. The condition (i.e., diagnosis) should be described. 
9.1.8 ECG Procedure  
Standard 12-lead ECGs will be recorded at timepoints specified in the Schedule of Study 
Procedures (Appendix A). Triplicate ECGs will be taken at each scheduled time. Additional 
unscheduled ECGs may be recorded where clinically necessary for subject safety. 
When an ECG is scheduled at the same time as blood draws or vital signs, then the blood draws 
and vital signs will take priority, and the ECG will be obtained within 0.5 hour before or after the 
scheduled blood draw/vital sign assessment. If an ECG coincides with a meal, ECG will take 
precedence, followed by the meal. 
All stationary 12-lead ECG machines will be supplied by the site. Subjects should be in a supine 
position following an approximate 10-minute rest period for ECG recordings. Should technical 
difficulties occur during the recording of the ECG, a reasonable attempt should be made to repeat 
the ECG shortly after the failed attempt.  
ECGs will be read automatically, and also, the investigator or sub-investigator will manually 
interpret the ECG using 1 of the following categories: within normal limits, abnormal but not CS, 
or abnormal and CS. Abnormal QTc readings will be manually recalculated and reported by the 
Investigator on the eCRF. All 12-lead ECGs will be stored for manual measurement of intervals, 
if necessary. Twelve-lead ECGs will be recorded using an ECG machine that automatically 
calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and 
QTcF and QTcB (Fridericia’s and Bazett’s correction) intervals. Paper ECG traces will be 
recorded for 10 seconds at a standard paper speed of 25 mm/sec, and gain of 10 m/mV or digital 
recordings will be used.  
One copy of the 12-lead ECG with the physician’s signature and date of assessment will be filed 
with the source documents and captured in the appropriate eCRF. If the original ECG is printed 
on thermal paper, the ECG report must be photocopied and certified. The photocopy will be filed 
with the original ECG in the source. 
All ECGs will be recorded at the time points detailed in Appendix A. 
9.1.9 Pharmacogenomic Sample Collection 
Every subject must sign ICF/be consented to the sampling of whole blood for pharmacogenomic 
analysis to participate in the study. 
One whole blood sample for DNA isolation and genotyping will be collected at time points 
specified in the Schedule of Study Procedures (Appendix A) into plastic dipotassium 
ethylenediamine-tetra acetic acid (K2EDTA) spray-coated tubes and stored under frozen 
conditions. In addition, two whole blood samples will be collected at time points specified in the 
Schedule of Study Procedures (Appendix A) for ribonucleic acid (RNA) pharmacogenomic 
analysis. The pre-dose RNA blood samples should be collected under fasted conditions and prior 
to any other blood collection. 


CVN766 
 
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DNA may be evaluated for the genetic contribution to how the drug is broken down or affects the 
body. This is called a “pharmacogenomics research study.” Specific purposes of this study include: 
• Identifying genetic reasons why certain people respond differently to CVN766 
• Finding out more information about how CVN766 works 
• Generating information needed for research, development, and regulatory approval of tests to 
predict response to CVN766 
• Identifying variations in genes related to the biological target of CVN766 
This information may be used, for example, to develop a better understanding of the safety and 
efficacy of CVN766 and other study medications and for improving the efficiency, design, and 
study methods of future research studies. 
The samples will be stored no longer than 15 years after completion of the CVN766 study and/or 
until the drug development of CVN766 is no longer actively pursued by the sponsor or its 
collaborators. No samples will be stored for longer than permitted by the applicable law, and 
samples will be destroyed upon notification from the sponsor. “Stored samples” in this context are 
defined as samples that are double coded (the samples are stripped of all personal identifying 
information but a key links the samples to the clinical data collected from the sample donor) and 
are used in the analysis of investigational drug or related drug. 
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; every 
subject must sign the ICF in order to participate in this study. DNA samples will be collected and 
may be used to evaluate drug metabolic enzyme and transporter polymorphisms that may 
contribute to the variability in the PK of CVN766. Also, since pharmacogenomics is an evolving 
science, many genes and their functions are not yet fully understood. Future data may suggest a 
role of some of these genes in drug response, which may lead to additional hypothesis-generating 
exploratory research and diagnostic development on stored samples. 
If necessary and feasible, a second aliquot of blood may be taken if isolation of DNA and RNA 
from the first sample was not successful or possible. 
Samples will be frozen at -70°C or lower and shipped separately on dry ice prior to extraction and 
storage at -70°C or lower. Samples should not be allowed to thaw until processed. 
Detailed instructions for the handling and shipping of samples are provided in a separate lab 
manual. 
Genotyping on collected samples may be deferred until after the completion of the study’s in-life 
activities. 
Each pharmacogenomic sample for a study subject should be identifiable on the requisition form 
with the 4-digit randomization number. 


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9.1.10 PK Sample Collection 
9.1.10.1 Collection of Blood for PK Sampling 
Blood samples for analysis of CVN766 plasma concentrations will be collected into chilled 
Vacutainers containing K2EDTA according to the schedule in Appendix A. Instructions for sample 
processing and shipment are provided in a separate lab manual. 
In all single-dose cohorts, serial blood samples to determine CVN766 concentrations in plasma 
will be collected according to Table 7. 
Table 6 
Collection of Blood Samples for PK Analysis in Single-Dose Cohorts 
Sample 
Type 
Dosing 
Day 
Time Post-dose (hours). 
Plasma 
1 
Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24-, 36-
, 48-, and 72-hours post-dose.  
 
In all cohorts for Part 2, serial blood samples for determination of CVN766 concentrations in 
plasma will be collected according to Table 8. 
 
 


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CVN766 
 
Study No. CVN766-101 
Page 45 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
Symbol/Term 
Definition 
Plasma 
λz 
Terminal elimination rate constant, calculated as the negative of the slope of the log-linear 
regression of the natural logarithm concentration-time curve during the terminal phase 
t1/2z 
Terminal elimination half-life, calculated as ln(2)/λz. 
tmax 
Time to reach Cmax. 
Vz/F 
 
Apparent volume of distribution during the terminal phase after extravascular 
administration, calculated as (CL/F)/λz. 
Vz/Fss 
Apparent volume of distribution during the terminal phase after extravascular 
administration at a steady-state, calculated as (CL/Fss)/λz 
CSF 
plasma: CSF ratio 
ratio of the drug concentration in plasma vs. CSF 
 
Additional PK parameters may be calculated as appropriate. 
 
 
 
 
 
 
 
 
9.1.12 Procedures for Clinical Laboratory Samples 
All samples will be collected in accordance with acceptable laboratory procedures on the 
days/times stipulated in the Schedule of Study Procedures (Appendix A). 
Table 6 lists the tests that will be obtained for each laboratory specimen. 
Table 10 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Urinalysis 
Special 
RBC 
WBC 
with 
differential  
     (% 
and 
absolute) 
Hemoglobin 
Hematocrit 
Platelets 
PT/INR 
ALT 
Albumin 
Alkaline 
phosphatase 
Lipase 
(d) 
AST 
Total 
bilirubin 
Direct 
bilirubin 
Total 
protein 
Creatinine 
Blood 
urea 
nitrogen 
Creatine 
kinase 
GGT 
Potassium 
Sodium 
Glucose 
Chloride 
Bicarbonate 
Calcium 
pH 
Specific 
gravity 
Protein 
Glucose 
Blood  
Nitrite 
Microscopic 
Analysis 
(only if positive dipstick 
results):  
RBC/high power field 
WBC/high power field 
Epithelial cells, casts etc. 
Prolactin 
TSH 
(and if abnormal) 
reflex FT4 
Diagnostic Screening: 


CVN766 
 
Study No. CVN766-101 
Page 46 of 81
Clinical Protocol – FINAL Version 1.0 
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CONFIDENTIAL 
Serum 
Urine/ Blood 
Serum hCG (a) 
FSH (b)  
Hepatitis panel, including HBsAg and anti-HCV (e) 
Human Immunodeficiency Virus (HIV) antibody 
Drug screen including amphetamines (AMP), 
barbiturates (BAR), benzodiazepines (BZO), 
cannabinoids, cocaine (COC), opiates (OPI), 
alcohol, 
cotinine 
© 
methamphetamines, 
methadone 
(MET), 
methylenedioxymethamphetamine (MDMA), 
phencyclidine (PCP), tetrahydrocannabinol 
(TCH) 
FT4= free T4, FSH= follicle-stimulating hormone, GGT=γ-glutamyl transferase, hCG= human chorionic 
gonadotropin, PT=prothrombin time, RBC=red blood cells, TSH= thyrotropin, WBC=white blood cells. 
(a) Serum hCG pregnancy test will be done at Screening, Check-in (Day -1), and Inpatient Discharge or Early 
Termination and at the Follow-up Visit if the subject is brought back to the clinic for re-evaluation. 
(b) FSH level will be obtained for female subjects at Screening if they are postmenopausal (i.e., last regular menstrual 
cycle >2 years) and not surgically sterile. The result must be >40 IU/L for the subject to be enrolled. 
(c) 
To 
be 
performed 
at 
Screening 
and 
Inpatient 
Check-in 
(Day 
-1). 
(d) To be performed at Day -1 and 24- and 48-hours post-dose. 
(e) Screening Visit only 
The local laboratory will perform all clinical laboratory tests. The results of laboratory tests will 
be returned to the investigator, who is responsible for reviewing and filing these results. All 
laboratory safety data will be transferred electronically to the sponsor or designee in the format 
requested by the sponsor. The investigator will maintain a copy of the laboratory accreditation and 
the reference ranges for the laboratory used.  
Laboratory reports must be signed and dated by the Investigator or sub-investigator, indicating that 
the report has been reviewed and any abnormalities have been assessed for clinical significance. 
Subjects will be referred to their primary care physician for follow-up of any clinically significant 
findings or where the investigator or medically trained sub-investigator deems appropriate. 
All CS laboratory abnormalities must be recorded as a PTE/AE in the subject’s source documents 
and on the appropriate eCRF. A CS laboratory abnormality that has been verified by retesting will 
be followed until the abnormality returns to an acceptable level or a satisfactory explanation has 
been obtained. 
If subjects experience ALT or AST >3 ×ULN, follow-up laboratory tests at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR should be performed within a 
maximum of 7 days and preferably within 48 to 72 hours after the abnormality was found. 
(Please refer to Section 7.5 for discontinuation criteria and Section 9.8.3 for the appropriate 
guidance on Reporting of Abnormal LFT in relation to ALT or AST >3 ×ULN in conjunction with 
total bilirubin >2 ×ULN). 
If the ALT or AST remains elevated >3 ×ULN on these 2 consecutive occasions, the investigator 
must contact the Medical Monitor for consideration of additional testing, close monitoring, 
possible discontinuation of study medication, discussion of the relevant subject details and possible 
alternative etiologies. The abnormality should be recorded as an AE (please refer to Section 9.8.3 
Reporting of Abnormal LFT for reporting requirements). 


CVN766 
 
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Page 47 of 81
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9.1.13 Contraception and Pregnancy Avoidance Procedure 
From the date of signing of ICF, throughout the duration of the study, and for 30 days after the last 
dose of study medication, females of childbearing potential* must use two acceptable methods of 
contraception and must agree not to donate eggs; Nonsterilized** male subjects who are sexually 
active with a female partner of childbearing potential* must use two acceptable method(s) of 
contraception throughout the duration of the study, and for 90 days after the last dose of study 
medication. In addition, males must be advised not to donate sperm for 90 days after the last dose 
of study medication. 
Females of childbearing potential are defined as any female who has experienced menarche and 
who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not 
postmenopausal.  
Menopause is defined as at least 2 years since last regular menses with an FSH>40 IU/L or at least 
5 years since last regular menses, confirmed before any study medication is implemented. Male 
subjects with potentially postmenopausal partners who are under the age of 55 years must use 
condoms unless their partner’s postmenopausal status has been confirmed by FSH level.  
**Sterilized males should be at least 90 days post-vasectomy and confirm that they have obtained 
documentation of the absence of sperm in the ejaculate. 
Acceptable and highly effective methods of contraception are: 
• 
Hormonal methods of contraception including oral contraceptives containing combined 
estrogen and progesterone, a vaginal ring, injectable and implantable hormonal 
contraceptives, intrauterine hormone-releasing system (e.g. Mirena) and progestogen-
only hormonal contraception associated with inhibition of ovulation 
• 
Nonhormonal intrauterine device (IUD) 
• 
Bilateral tubal occlusion 
• 
Vasectomised subject/partner with documented azoospermia 90 days after procedure, 
if that partner is the sole sexual partner 
 
 For female participants, hormonal contraceptives should begin at least 1 month prior to screening 
to ensure contraceptive is in full effect.  
Complete abstinence, defined as the complete avoidance of heterosexual intercourse - is an 
acceptable form of contraception if used consistently throughout the duration of study and for the 
durations after dosing specified for males and females above. It is not necessary to use any other 
method of contraception when complete abstinence is elected. Females of childbearing potential 
who choose complete abstinence must continue to have pregnancy tests as per protocol. The 
reliability of sexual abstinence needs to be evaluated by the Investigator in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the subject. 
Subjects will be provided with information on acceptable methods of contraception as part of the 
subject's informed consent process and will be asked to sign an ICF stating that they understand 
the requirements for avoidance of pregnancy, egg donation, and sperm donation during the study.  
 


CVN766 
 
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Page 48 of 81
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CONFIDENTIAL 
 
9.1.14 Pregnancy 
Women who are pregnant or breastfeeding will not be included in this study.  
If any subject is found to be pregnant during the study, she should be withdrawn, and any sponsor-
supplied drug should be immediately discontinued. In addition, any pregnancies in the partner of 
a male subject during the study or for 90 days after the last dose should also be recorded following 
authorization from the subject’s partner.  
If the pregnancy occurs during administration of active study medication, e.g., after Visit 1 or 
within 30 days of the last dose of active study medication, the pregnancy should be reported 
immediately, using a pregnancy notification form, to the contact listed in Section 1.0. 
Should the pregnancy occur during or after administration of the blinded drug, the investigator 
must inform the subject of their right to receive treatment information. If the subject chooses to 
receive unblinded treatment information, the individual blind should be broken by the investigator. 
Subjects randomized to placebo need not be followed. 
If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time she became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable). 
All reported pregnancies will be followed up to the final outcome using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation 
after the birth of the child will also be conducted for 8 weeks. 
9.1.15 Documentation of Screen Failure 
Investigators must account for all subjects who sign ICF. If the subject is not eligible at this visit, 
the investigator should complete the eCRF screen failure form. 
The primary reason for screen failure is recorded in the eCRF using the following categories: 
• PTE/AE 
• Did not meet inclusion criteria or did meet exclusion criteria 
• Significant protocol deviation 
• Lost to follow-up 
• Voluntary withdrawal 
• Study termination 
• Other 
Subject numbers assigned to subjects who fail screening should not be reused.  
If a subject fails screening, but is later successfully rescreened, the data for the subject will be 
entered as if these were two separate subjects. Therefore, the data should be entered as follows: 
1. The screen failure data should be entered as a screen failure subject. 


CVN766 
 
Study No. CVN766-101 
Page 49 of 81
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CONFIDENTIAL 
2. Rescreened subjects should be assigned a new subject number and treated as a stand-alone 
subject. 
9.1.16 Documentation of Randomization 
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for randomization into the treatment phase. 
If the subject is found to be not eligible for randomization, the investigator should record the 
primary reason for failure on the applicable eCRF. 
9.2 
Monitoring Subject Treatment Compliance 
Study medication will be administered while subjects are under observation in the clinical research 
unit. Following administration of the study medication, appropriate mouth and/or hand checks will 
be performed to ensure that the dose is swallowed and noted in the source document. The date and 
time of each dose will be recorded in the source documents and on the eCRFs. An inventory of the 
study medication supplies dispensed will be performed by the site pharmacist or authorized study 
designee and recorded onto the Drug Accountability Log in the subject’s source document records 
or equivalent. The exact dose time of consecutive subjects may be staggered to facilitate logistics 
at the site. 
9.3 
Schedule of Observations and Procedures 
The study-related procedures schedule for all evaluations is shown in Appendix A and is not 
duplicated in the following sections.  
9.3.1 Screening 
Subjects will be screened within 28 days prior to randomization. Subjects will be screened in 
accordance with predefined inclusion and exclusion criteria as described in Section 7.0. See 
Section 9.1.15 for procedures for documenting screening failures. Subjects who are screening 
failures may be screened a second time if their reason for failing screening is thought to be 
resolved. Rescreened subjects will receive a new Screening number. 
9.3.2 Inpatient Check-In 
All subjects will be admitted to the study clinic the day prior to randomization and first dose.  
Subjects participating in the food effect cohorts will also check into the study clinic the day prior 
to the scheduled dosing. 
9.3.3 Final Visit (discharge day from clinic) 
Subjects will be confined to the study clinic for the duration of the treatment period to permit 
supervised dosing of study drug and repeat study assessments.  Subjects participating in the single-
dose study and food effect assessment will be discharged no sooner than 48 hours post-dose, and 
subjects participating in the multiple-dose study will be discharged no sooner than 48 hours 
following their last dose.   
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 


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Clinical Protocol – FINAL Version 1.0 
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CONFIDENTIAL 
9.3.4 Early Termination 
Subjects who discontinue dosing or decide to check out of the study clinic early will be advised to 
allow the Investigator (or authorized designees) to complete early termination assessments for 
safety purposes prior to discharge. The reason for discontinuation must be documented in the 
source document and eCRF.  
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 
9.3.5 Follow-up Visit  
The Follow-up Visit will occur by telephone approximately 14 days (±2) after the final dose of 
study drug for the SAD cohorts and MAD cohorts unless abnormal CS findings were observed 
upon discharge or the SRG has determined additional PK sampling timepoints are indicated. In 
these cases, subjects must then be brought back to the clinic for re-evaluation per the investigator’s 
discretion.  
9.4 
Biological Sample Retention and Destruction  
In all cohorts except S3 (fed), blood serum will be obtained on Day -1 and Day 2, and the collected 
serum will be stored at -70C to enable additional, retrospective analyses as needed. Samples will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. 
Blood specimens for genome/gene analysis will be collected as described in Section 9.1.12, 
Pharmacogenomic Sample Collection. After extraction and purification, the genetic material will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. Blood and urine samples for PK analysis will be 
collected as described in Section 9.1.12, PK Sample Collection.  Once PK analysis is complete, 
backup plasma and urine samples will be preserved and retained at a biorepository selected by the 
sponsor for up to, but not longer than, 15 years or as required by applicable law, to enable the 
conduct of exploratory, qualitative, metabolite identification studies or measurement of target 
related biomarkers, should the sponsor decide these are informative. The sponsor has put a system 
to protect the subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction. 
The sample will be labeled with a unique sample identifier similar to labeling in the main study 
but using a code different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 
code numbers; the samples are stripped of all personally identifying information, but a key linking 
the samples to clinical analysis data exists. This link means that the subject may be identified but 
only indirectly. The code numbers will be kept secure by or on behalf of the Sponsor. 
Subjects who consented and provided a pharmacogenomic sample for DNA and RNA analysis can 
withdraw their consent and request disposal of a stored sample at any time prior to analysis. The 
Investigator will notify the sponsor of any subject who has withdrawn consent for the DNA and 
RNA analysis. 


CVN766 
 
Study No. CVN766-101 
Page 51 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
9.5 
Blood Volume 
Direct venipuncture or intravenous cannula is the preferred method of blood collection. Any other 
method will need to be approved by the sponsor. The maximum volume of blood at any single day 
is approximately 111 mL, with the maximum amount not to exceed 500mL for the duration of 
study participation.  
9.6 
CSF Volume 
CSF will be collected by lumbar puncture, performed by a skilled and qualified individual. The 
maximum volume of CSF to be collected will be approximately 10 mL per subject.  
9.7 
Definitions 
9.7.1 PTE 
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed the ICF to participate in a study but prior to administration of any study medication; it does 
not necessarily have to have a causal relationship with study participation. 
9.7.2 AE 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (e.g., a CS abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a drug whether or not it is 
considered related to the drug. 
9.7.3 Additional Points to Consider for PTEs and AEs 
An untoward finding generally may: 
• Indicate a new diagnosis or unexpected worsening of a pre-existing condition. (Intermittent 
events for pre-existing conditions underlying disease should not be considered PTEs or AEs) 
• Necessitate therapeutic intervention 
• Require an invasive diagnostic procedure 
• Require discontinuation or a change in dose of study medication or a concomitant medication 
• Be considered unfavorable by the investigator for any reason 
• PTEs/AEs caused by a study procedure (e.g., a bruise after blood draw) should be recorded as 
a PTE/AE 
Diagnoses vs. signs and symptoms: 
• Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as a PTE(s) or as an AE(s). 


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Laboratory values and ECG findings: 
• Changes in laboratory values or ECG parameters are only considered to be PTEs or AEs if 
they are judged to be CS (i.e., if some action or intervention is required or if the investigator 
judges the change to be beyond the range of normal physiologic fluctuation). A laboratory re-
test and/or continued monitoring of an abnormal value are not considered an intervention. In 
addition, repeated or additional noninvasive testing for verification, evaluation, or monitoring 
of an abnormality is not considered an intervention 
• If abnormal laboratory values or ECG findings are the results of pathology for which there is 
an overall diagnosis (e.g., increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as a PTE or as an AE 
Pre-existing conditions: 
• Pre-existing conditions (present at the time of signing of the ICF) are considered concurrent 
medical conditions and should NOT be recorded as PTEs or AEs. Baseline evaluations (e.g., 
laboratory tests, ECG, X-rays, etc.) should NOT be recorded as PTEs unless related to study 
procedures.  
• If a subject has a pre-existing episodic condition (e.g., asthma, epilepsy), any occurrence of an 
episode should only be captured as a PTE/AE if the episodes become more frequent, serious, 
or severe in nature; that is, investigators should ensure that the AE term recorded captures the 
change in the condition from Baseline (e.g., “worsening of…”) 
• If a subject has a concurrent degenerative condition (e.g., cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater extent 
than that which would be expected. Again, investigators should ensure that the AE term 
recorded captures the change in the condition (e.g., “worsening of…”) 
Worsening of PTEs or AEs: 
• If the subject experiences a worsening or complication of a PTE after starting administration 
of the study medication, the worsening or complication should be recorded appropriately as an 
AE.  
• If the subject experiences a worsening or complication of an AE after any change in study 
medication, the worsening or complication should be recorded as a new AE. Changes in 
severity of AEs /Serious PTEs: 
• If the subject experiences changes in the severity of an AE/serious PTE, the event should be 
captured once with the maximum severity recorded 
Preplanned surgeries or procedures: 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to signing informed 
consent are not considered PTEs or AEs. However, if a preplanned procedure is performed 
early (e.g., as an emergency) due to a worsening of the pre-existing condition, the worsening 
of the condition should be captured appropriately as a PTE or an AE. Complications resulting 
from any planned surgery should be reported as AEs. 
Elective surgeries or procedures: 


CVN766 
 
Study No. CVN766-101 
Page 53 of 81
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CONFIDENTIAL 
• Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as PTEs or AEs, but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs 
Overdose: 
• Cases of overdose with any medication without manifested side effects are NOT considered 
PTEs or AEs, but instead will be documented on an Overdose page of the eCRF. Any 
manifested side effects will be considered PTEs or AEs and will be recorded on the AE page 
of the eCRF 
9.7.4 SAEs 
An SAE is defined as any untoward medical occurrence that at any dose: 
1. Results in DEATH. 
2. Is LIFE-THREATENING 
• The term “life-threatening” refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization 
4. Results in persistent or significant DISABILITY/INCAPACITY 
5. Leads to a CONGENITAL ANOMALY/BIRTH DEFECT 
6. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following: 
• May require intervention to prevent items 1 through 5 above 
• May expose the subject to danger, even though the event is not immediately life-
threatening or fatal or does not result in hospitalization 
• Includes any event or synonym described in the Medically Significant AE List (Table 11) 


CVN766 
 
Study No. CVN766-101 
Page 54 of 81
Clinical Protocol – FINAL Version 1.0 
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CONFIDENTIAL 
Table 11 
Medically Significant AE List (categorized as Serious Adverse Events) 
Term 
Acute respiratory failure/acute respiratory distress 
syndrome 
Hepatic necrosis 
Torsade de pointes / ventricular fibrillation / 
ventricular tachycardia 
Acute liver failure 
Anaphylactic shock 
Malignant hypertension 
Acute renal failure 
Convulsive seizure 
Pulmonary hypertension 
Agranulocytosis 
Pulmonary fibrosis 
Aplastic anemia 
Confirmed or suspected endotoxin shock 
Toxic 
epidermal 
necrolysis/Stevens-Johnson 
syndrome 
Confirmed or suspected transmission of infectious agent 
by a medicinal product 
 
Neuroleptic 
malignant 
syndrome 
/ 
malignant 
hyperthermia 
 
Spontaneous abortion/stillbirth and fetal death 
 
PTEs that fulfill 1 or more of the serious criteria above are also to be considered SAEs and should 
be reported and followed up in the same manner (see Sections 9.8.1 and 9.8.2). 
9.7.5 Severity of PTEs and AEs 
The different categories of intensity (severity) are characterized as follows: 
Mild: 
The event is transient and easily tolerated by the subject. 
Moderate: 
The event causes the subject discomfort and interrupts the subject’s usual activities. 
Severe: 
The event causes considerable interference with the subject’s usual activities. 
9.7.6 Causality of AEs 
The relationship of each AE to study medication(s) will be assessed using the following categories: 
Related: 
An AE that follows a reasonable temporal sequence from the administration of a drug 
(including the course after withdrawal of the drug), or for which possible involvement of the 
drug can be argued, although factors other than the drug, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments, may also be responsible. 
Not Related: 
An AE that does not follow a reasonable temporal sequence from the administration of a drug 
and/or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments. 
9.7.7 Relationship to Study Procedures 
Relationship (causality) to study procedures should be determined for all PTEs and AEs. 
The relationship should be assessed as Related if the investigator considers that there is a 
reasonable possibility that an event is due to a study procedure. Otherwise, the relationship should 
be assessed as Not Related. 


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9.7.8 Start Date  
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician. 
9.7.9 Stop Date  
The stop date of the AE/serious PTE is the date at which the subject recovered, the event resolved 
but with sequelae, or the subject died. 
9.7.10 
Frequency  
Episodic AEs/serious PTE (e.g., vomiting) or those which repeatedly occur over a period of 
consecutive days are intermittent. All other events are continuous. 
9.7.11 
Action Concerning Study Medication  
• Drug withdrawn – a study medication is stopped due to the particular AE 
• Dose not changed – the particular AE did not require stopping a study medication 
• Unknown – only to be used if it has not been possible to determine what action has been taken 
• Not Applicable – a study medication was stopped for a reason other than the particular AE, 
e.g., the study has been terminated, the subject died, dosing with study medication was already 
stopped before the onset of the AE 
9.7.12 
Outcome 
• Recovered/Resolved – Subject returned to first assessment status with respect to the 
AE/serious PTE 
• Recovering/Resolving – the intensity is lowered by one or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved, but has not 
returned to the normal range or to baseline; the subject died from a cause other than the 
particular AE/serious PTE with the condition remaining “recovering/resolving” 
• Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the 
intensity of the diagnosis, signs/ symptoms, or laboratory value on the last day of the observed 
study period had got worse than when it started; is an irreversible congenital anomaly; the 
subject died from another cause with the particular AE/serious PTE state remaining “Not 
recovered/not resolved” 
• Resolved with sequelae – the subject recovered from an acute AE/serious PTE but was left 
with permanent/significant impairment (e.g., recovered from a cardiovascular accident but 
with some persisting paresis 
• Fatal – the AEs/PTEs which are considered as the cause of death 
• Unknown – the course of the AE/serious PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study 


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9.8 
Procedures 
9.8.1 Collection and Reporting of AEs 
9.8.1.1 PTE and AE Collection Period 
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication Day 1 
or until screen failure. For subjects who discontinue prior to study medication administration, PTEs 
will be collected for the duration of study participation. 
Collection of AEs will commence from the time that the subject is first administered study 
medication Day 1. Routine collection of AEs will continue until 14 days following last dose. 
9.8.1.2 PTE and AE Reporting 
At each study visit, the investigator or designee will assess whether any subjective AEs have 
occurred. A neutral question, such as “How have you been feeling since your last visit?” may be 
asked. Subjects may report AEs occurring at any other time during the study. Subjects 
experiencing a serious PTE must be monitored until the symptoms subside and any clinically 
relevant changes in laboratory values have returned to baseline or there is a satisfactory explanation 
for the change. Non-serious PTEs, related or unrelated to the study procedure, need not be followed 
up for the purposes of the protocol. 
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or until there is a satisfactory explanation for the 
changes observed. All PTEs and AEs will be documented in the PTE/AE page of the eCRF, 
whether or not the investigator concludes that the event is related to the drug treatment. The 
following information will be documented for each event: 
1. Event term. 
2. Start and stop date and time. 
3. Frequency. 
4. Severity. 
5. Investigator’s opinion of the causal relationship between the event and administration of study 
medication(s) (related or not related) (not completed for PTEs). 
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details of 
the suspected procedure. 
7. Action concerning study medication (not applicable for PTEs). 
8. Outcome of event. 
9. Seriousness. 


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9.8.2 Collection and Reporting of SAEs 
When an SAE occurs through the AE collection period it should be reported according to the 
following procedure: 
An SAE form must be completed in English and signed by the investigator immediately or within 
24 hours of the first onset or notification of the event. The information should be completed as 
fully as possible but contain, at a minimum: 
• A short description of the event and the reason why the event is categorized as serious 
• Subject identification number 
• Investigator’s name 
• Name of the study medication(s) 
• Causality assessment 
The SAE form should be transmitted within 24 hours to the attention of the contact listed in Section 
1.0.  
Any SAE spontaneously reported to the investigator following the AE collection period should be 
reported to the sponsor if considered related to study participation. 
Reporting of Serious PTEs will follow the procedure described for SAEs. 
9.8.3 Reporting of Abnormal LFT 
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an LFT Increases eCRF must be completed 
providing additional information on relevant recent history, risk factors, clinical signs and 
symptoms, and results of any additional diagnostic tests performed. 
If a subject is noted to have ALT or AST >3 ×ULN and total bilirubin >2 ×ULN for which an 
alternative etiology has not been identified, the event should be recorded as an SAE and reported 
as per Section 9.8.2. The investigator must contact the Medical Monitor for discussion of the 
relevant subject details and possible alternative etiologies, such as acute viral hepatitis A or B or 
other acute liver disease or medical history/concurrent medical conditions. Follow-up laboratory 
tests as described in Section 9.1.8 must also be performed. In addition, an LFT Increases eCRF 
must be completed and transmitted with the SAE form (as per Section 9.8.3). 
9.9 
Follow-up of SAEs 
If information is not available at the time of the first report becomes available at a later date, the 
investigator should complete a follow-up SAE form or provide other written documentation and 
fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital notes 
(e.g., ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee, if requested. 
All SAEs should be followed up until resuspension or permanent outcome of the event. The 
timelines and procedures for follow-up reports are the same as those for the initial report. 


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9.9.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory 
Authorities  
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities and IRBs or IECs, as 
applicable, in accordance with national regulations in the countries where the study is conducted. 
Relative to the first awareness of the event by/or further provision to the sponsor or sponsor’s 
designee, SUSARs will be submitted to the regulatory authorities as an expedited report within 7 
days for fatal and life-threatening events and 15 days for other serious events, unless otherwise 
required by national regulations. The sponsor will also prepare an expedited report for other safety 
issues that might materially alter the current benefit-risk assessment of an investigational 
medicinal product or that would be sufficient to consider changes in the investigational medicinal 
products administration or in the overall conduct of the trial. The investigational site also will 
forward a copy of all expedited reports to his or her IRB or IEC in accordance with national 
regulations. 


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10.0 
STUDY-SPECIFIC COMMITTEES 
The Safety Review Group (SRG) will be comprised of the Investigator, Medical Monitor, 
Cerevance Medical Officer and may include other sponsor representatives. A pharmacokineticist 
and other subject matter experts may participate as needed. Responsibilities of the SRG are 
outlined in Section 6.1.3. 


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11.0 
DATA HANDLING AND RECORDKEEPING 
AEs, PTEs, medical history, and concurrent conditions will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization 
(WHO) Drug Dictionary. All terms will be coded using the dictionary version available at the start 
of the study. 
11.1 
CRFs (Electronic) 
Completed eCRFs are required for each subject who signs an informed consent. 
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRF. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. Data are transcribed directly onto eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by sponsor 
personnel (or designees) and will be answered by the site.  
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for change. Reasons for significant corrections should additionally be included.  
The Investigator must review the eCRFs for completeness and accuracy and must sign and date 
the appropriate eCRFs as indicated. Furthermore, the investigator must retain full responsibility 
for the accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The sponsor or its designee will be permitted to review the subject’s medical 
and hospital records pertinent to the study to ensure the accuracy of the eCRFs. The completed 
eCRFs are the sole property of the sponsor and should not be made available in any form to third 
parties, except for authorized representatives of appropriate governmental health or regulatory 
authorities, without the written permission of the sponsor. 
11.2 
Record Retention 
The investigator agrees to keep the records stipulated in Section 11.2 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated ICFs, subject authorization forms regarding the use of 
personal health information (if separate from the ICFs), an electronic copy of eCRFs, including 
the audit trail, and detailed records of drug disposition to enable evaluations or audits from 
regulatory authorities, the sponsor or its designees. Any source documentation printed on 
degradable thermal sensitive paper should be photocopied by the site and filed with the original in 
the subject’s chart to ensure long-term legibility. Furthermore, ICH E6 Section 4.9.5 requires the 
investigator to retain essential documents specified in ICH E6 (Section 8) until at least 2 years 
after the last approval of a marketing application for a specified drug indication being investigated 
or, if an application is not approved, until at least 2 years after the investigation is discontinued 
and regulatory authorities are notified. In addition, ICH E6 Section 4.9.5 states that the study 


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records should be retained until an amount of time specified by applicable regulatory requirements 
or for a time specified in the Clinical Study Site Agreement between the investigator and sponsor. 
Refer to the Phase 1 Site Specifications document for the sponsor’s requirements on record 
retention. The investigator should contact and receive written approval from the sponsor before 
disposing of any such documents. 


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12.0 
STATISTICAL METHODS 
12.1 
Statistical and Analytical Plans 
A statistical analysis plan (SAP) will be prepared and finalized prior to unblinding of the subject’s 
treatment assignment. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all study objectives. 
A targeted data review will be conducted prior to unblinding of the subject’s treatment assignment. 
This review will assess the accuracy and completeness of the study database, subject evaluability, 
and appropriateness of the planned statistical methods. 
12.1.1 Analysis Sets 
Safety Set 
The Safety Analysis Set will consist of all subjects who are enrolled and receive study drug. 
Subjects in this analysis set will be used for demographic, baseline characteristics, and safety 
summaries. 
PK Set 
The PK set will consist of all subjects who receive study drug and have at least 1 measurable 
plasma concentration. 
If any subjects are found to be non-compliant in dosing schedule or with incomplete data, a 
decision will be made on a case-by-case basis as to their inclusion in the analysis but will be 
presented in the subject listings. 
12.1.2 Analysis of Demographics and Other Baseline Characteristics 
Descriptive statistics (N, mean, SD, median, minimum, and maximum) will be generated for 
continuous demographic variables and baseline characteristics variables (age, height, weight, and 
BMI) for pooled placebo, CVN766 dose level, CVN766 overall, and overall. The number and 
percentage of subjects in each class of the categorical demographic variables and baseline 
characteristics variables (gender, ethnicity, and race) will be tabulated for pooled placebo, each 
CVN766 dose level, CVN766 overall, and overall. Individual subject demographic and baseline 
characteristics data will be listed. 
Demographic variables of screen failure subjects and reasons for screen failures will be 
summarized overall for subjects who are screened but not enrolled in the study. Individual 
demographic characteristics, date of informed consent, and reason for screen failure will be listed. 
12.1.3 PK Analysis 
The concentration of CVN766 in plasma, and CSF will be summarized by dose over each scheduled sampling time 
using descriptive statistics. Individual concentration data versus time will be presented in a data listing. Individual and 
mean plasma and CSF concentration data will be presented graphically.  Descriptive statistics (arithmetic mean, SD, 
median, minimum and maximum) will be used to summarize the plasma and CSF PK parameters for CVN766. In 
addition, geometric mean and coefficient of variation will be computed 
The effect of fed/fasting state on PK and bioavailability of CVN766 will be characterized. 


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Plots of Cmax and AUCs, as well as dose-normalized Cmax and AUCs, versus doses, will be 
generated. 
Dose proportionality will be tested for CVN766 Cmax and AUCs using a power model.  
A more detailed analysis will be presented in the SAP. 
12.1.4 Safety Analysis 
12.1.4.1 AEs 
All AEs will be coded by system organ class (SOC) and preferred term (PT) using MedDRA. 
Treatment-emergent AEs with onset occurring within 30 days (onset date – last date of dose +1 
≤30) after study drug administration will be listed and included in the summary tables. Treatment-
emergent AEs will be summarized by pooled placebo, each CVN766 dose level and CVN766 
overall by SOC and PT. The following summary tables will be included in the report: summary of 
TEAEs and drug-related AEs, relationship of AEs to study drug (related vs. not-related), severity 
of AEs, and related AEs. AEs leading to study drug discontinuation and SAEs will be listed. Data 
listings will be provided for all AEs, including PTE, TEAEs, AEs leading to study drug 
discontinuation, and SAEs. All AEs will be listed. 
12.1.4.2 Clinical Laboratory Evaluation 
Individual results of laboratory tests from hematology, chemistry, and urinalysis that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and change from baseline to post-dose 
laboratory data will be summarized for pooled placebo, each CVN766 dose level, and CVN766 
overall. All clinical laboratory data will be listed. 
12.1.4.3 Vital Signs 
Individual results of vital signs that are abnormal and CS will be summarized and listed. Baseline, 
post-dose, and changes from Baseline in vital sign measurements will be summarized by pooled 
placebo, each CVN766 dose level, and CVN766 overall. All vital sign data will be provided in the 
data listings. 
12.1.4.4 ECGs 
Individual results of quantitative ECG parameters from the 12-lead safety ECGs that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and changes from baseline in 
quantitative ECG parameters will be summarized by pooled placebo, each CVN766 dose level, 
and CVN766 overall. Shift tables may be generated for the investigator’s ECG interpretations that 
changed from baseline to the post-dose collections by the above groups. All ECG data will be 
provided in the data listings. 
12.1.4.5 Other Variables 
Physical exam findings and suicidal assessments will be presented in data listings. 
12.2 
Interim Analysis and Criteria for Early Termination 
No interim analysis is planned. 


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12.3 
Determination of Sample Size 
The sample size chosen of 8 subjects per cohort (6 active: 2 placebo) is considered to be sufficient 
for the evaluation of the safety, tolerability, and PK of each cohort. The sample size was not based 
on statistical power considerations.  


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13.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Study-Site Monitoring Visits 
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution guarantee access to source documents by the sponsor or its 
designee (contract research organization) and by the IRB or IEC. 
All aspects of the study and its documentation will be subject to review by the sponsor or designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, 
study medication, subject medical records, informed consent documentation, documentation of 
subject authorization to use personal health information (if separate from the ICFs), and review of 
eCRFs and associated source documents. It is important that the investigator and other study 
personnel are available during the monitoring visits and that sufficient time is devoted to the 
process. 
13.2 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
designee (and IRB or IEC, as required) to determine the appropriate course of action. There will 
be no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria. 
The site should document all protocol deviations in the subject’s source documents. In the event 
of a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessment. A Protocol Deviation Form should be completed by the site and signed by the sponsor 
or designee for any significant deviation from the protocol. 
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. Table 12 
defines the windows allowed for sample collections.  
Protocol Deviation Forms are to be completed for PK samples collected outside of the following 
intervals: 
Table 12 
Windows for PK Blood Sample Collection 
Minutes 
Nominal Sampling Time 
no more than 15 minutes pre-dose 
0 hour 
±5 
immediately post-dose to ≤6 hours 
±10 
>6 hours to ≤12 hours post-dose 
±15 
>12 hours to ≤24 hours 
±30 
>24 hours 
 


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13.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing 
visit. The auditor may ask to visit the facilities where laboratory samples are collected, where the 
medication is stored and prepared, and any other facility used during the study. In addition, there 
is the possibility that this study may be inspected by regulatory agencies, including those of 
Australia (i.e., Therapeutic Goods Administration [TGA]) and foreign governments (e.g., the 
FDA, the United Kingdom Medicines and Healthcare products Regulatory Agency, the 
Pharmaceuticals and Medical Devices Agency of Japan). If the study site is contacted for an 
inspection by a regulatory body, the sponsor should be notified immediately. The investigator and 
institution guarantee access for quality assurance auditors to all study documents as described in 
Section 13.1. 


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14.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual subjects (i.e., subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, 
and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct the study 
according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the “Responsibilities of the Investigator” that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities. 
14.1 
IRB and/or IEC Approval 
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. Those Americas sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services. 
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the ICFs, and, if applicable, subject recruitment materials and/or advertisements and other 
documents required by all applicable laws and regulations must be submitted to a central or local 
IRB or IEC for approval. The IRB’s or IEC’s written approval of the protocol and subject informed 
consent must be obtained and submitted to the sponsor or designee before the commencement of 
the study (i.e., before shipment of the sponsor-supplied drug or study-specific screening activity). 
The IRB or IEC approval must refer to the study by exact protocol title, number, and version date; 
identify versions of other documents (e.g., ICF) reviewed; and state the approval date. The sponsor 
will ship drug/notify site once the sponsor has confirmed the adequacy of site regulatory 
documentation and, when applicable, the sponsor has received permission from a competent 
authority to begin the trial. Until the site receives drug/notification, no protocol activities, 
including screening may occur. 
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by subjects, local safety reporting requirements, reports, and 
updates regarding the ongoing review of the study at intervals specified by the respective IRB or 
IEC, and submission of the investigator’s final status report to IRB or IEC. All IRB and IEC 
approvals and relevant documentation for these items must be provided to the sponsor or its 
designee. 
Subject incentives should not exert undue influence on participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor. 


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14.2 
Subject Information, Informed Consent, and Subject Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
applicable laws and regulations. The ICF, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and disclosures 
of the subject’s personal and personal health information for purposes of conducting the study. 
The ICF and the subject information sheet (if applicable) further explain the nature of the study, 
its objectives, and potential risks and benefits, as well as the date informed consent is given. The 
ICF will detail the requirements of the subject and the fact that he or she is free to withdraw at any 
time without providing a reason and without prejudice to their other medical care. 
The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and if applicable, the subject authorization form. The ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) must be approved by both the IRB or IEC 
and the sponsor prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject. It is the 
responsibility of the investigator to explain the detailed elements of the ICF, subject authorization 
form (if applicable), and subject information sheet (if applicable) to the subject. Information should 
be given in both oral and written form whenever possible and in the manner deemed appropriate 
by the IRB or IEC. In the event the subject is not capable of rendering adequate written informed 
consent, then the subject’s legally acceptable representative may provide such consent for the 
subject in accordance with applicable laws and regulations. 
The subject, or the subject’s legally acceptable representative, must be given ample opportunity 
to: (1) inquire about details of the study and (2) decide whether or not to participate in the study. 
If the subject, or the subject’s legally acceptable representative, determines he or she will 
participate in the study, then the ICF and subject authorization form (if applicable) must be signed 
and dated by the subject, or the subject’s legally acceptable representative, at the time of consent 
and prior to the subject entering into the study. The subject or the subject’s legally acceptable 
representative should be instructed to sign using their legal names, not nicknames, using blue or 
black ballpoint ink. The investigator must also sign and date the ICF and subject authorization (if 
applicable) at the time of consent and prior to the subject entering into the study; however, the 
sponsor may allow a designee of the investigator to sign to the extent permitted by applicable law. 
Once signed, the original ICF, subject authorization form (if applicable), and subject information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document 
the date the subject signs the informed consent in the subject’s medical record. Copies of the signed 
ICF, the signed subject authorization form (if applicable), and the subject information sheet (if 
applicable) shall be given to the subject. 
All revised ICFs must be reviewed and signed by relevant subjects or the relevant subject’s legally 
acceptable representative in the same manner as the original informed consent. The date the revised 
consent was obtained should be recorded in the subject’s medical record, and the subject should 
receive a copy of the revised ICF. 


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Subjects who consented and provided a pharmacogenomic sample for DNA analysis can withdraw 
their consent and request disposal of a stored sample at any time prior to analysis. Notify sponsor 
of consent withdrawal. 
14.3 
Subject Confidentiality 
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the sponsor’s clinical study database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or 
date of birth, and subject initials may be used to verify the subject and the accuracy of the subject’s 
unique identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (e.g., FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s study participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process (see Section 14.2). 
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (i.e., subject name, address, and other identifier fields 
not collected on the subject’s eCRF). 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy 
14.4.1 Publication and Disclosure 
The investigator is obliged to provide the sponsor with complete test results and all data derived 
by the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and/or advertisements, is the sole responsibility of the sponsor. 
The sponsor may publish any data and information from the study, including data and information 
generated by the investigator, without the consent of the investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and review 
of the document. All publications and presentations must be prepared in accordance with this 
section and the Clinical Study Site Agreement. In the event of any discrepancy between the 
protocol and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail. 
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. 


CVN766 
 
Study No. CVN766-101 
Page 70 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
14.4.2 Clinical Trial Registration  
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations, and guidance, the sponsor will register this clinical trial 
on ClinicalTrials.gov (and possibly on other publicly accessible websites) before the start of study.  
Sponsor contact information, along with the investigator’s city, state, country, and recruiting 
status, will be registered and available for public viewing. Once subjects receive investigator 
contact information, they may call the site and request enrollment into the trial. The investigative 
site(s) are encouraged to handle such trial inquiries according to their established subject screening 
process. If the caller asks additional questions beyond the topic of trial enrollment, they should be 
referred to the sponsor.  
14.4.3 Clinical Trial Results Disclosure  
If required at the conclusion of the study, the sponsor will post the results on ClinicalTrials.gov or 
other publicly accessible websites, as required by applicable national and local laws and/or 
regulations. 
14.5 
Insurance and Compensation for Injury 
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject compensation 
and treatment for injury. If the investigator has questions regarding this policy, he or she should 
contact the sponsor or sponsor’s designee. 


CVN766 
 
Study No. CVN766-101 
Page 71 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
15.0 
REFERENCES 
FDA Guidance for Industry: Food-effect bioavailability and fed bioequivalence studies (Dec 
2002). 
FDA Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials 
for Therapeutics in Adult Healthy Volunteers. US Dept of Health and Human Services, Food 
and Drug Administration, Center for Drug Evaluation and Research. 06 July 2005. Publication 
No. 5541. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. First-in-human study with ACT-
539313, a novel selective orexin-1 receptor antagonist. Br J Clin Pharmacol. 2020 
Jul;86(7):1377-1386. doi: 10.1111/bcp.14251. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. Multiple-dose clinical pharmacology 
of the selective orexin-1 receptor antagonist ACT-539313. Prog Neuropsychopharmacol Biol 
Psychiatry. 2021 Jun 8;108:110166. doi: 10.1016/j.pnpbp.2020.110166.  
Salvadore G, Bonaventure P, Shekhar A, Johnson PL, Lord B, Shireman BT, Lebold TP, 
Nepomuceno D, Dugovic C, Brooks S, Zuiker R, Bleys C, Tatikola K, Remmerie B, Jacobs 
GE, Schruers K, Moyer J, Nash A, Van Nueten LGM, Drevets WC. Translational evaluation 
of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for 
panic in rodents and humans. Transl Psychiatry. 2020 Sep 7;10(1):308. doi: 10.1038/s41398-
020-00937-9. 
 


CVN766 
 
Study No. CVN766-101 
Page 72 of 81
Clinical Protocol  - Final  Version 1.0 
September 2021
 
CONFIDENTIAL 
Appendix A Schedule of Study Procedures  
 


CVN766 
 
Study No. CVN766-101 
Page 73 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
 
SAD Cohorts 1, 2, 4, 5 
Screening 
Check-in Dosing & Observation Discharge (a) 
utpatient 
Visit 
Early 
Termination 
Follow-up 
Study Day:  
-28 to -2  
Day -1  
Day 1 Day 2 
Day 3 
Day 4 
Day 8 
Day 14 (±2) (b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Demographics and medical history 
X 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 
Abbreviated Neuro Exam 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination  
X 
X 
 
 
 
X  
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight, height, and BMI (d) 
X 
X 
 
 
 
X 
X 
X 
 
Urine drug & cotinine screen 
X 
X 
 
 
 
 
 
 
 
Concomitant medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical conditions 
X 
X 
 
 
 
 
 
 
 
Clinical laboratory tests (f) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hepatitis panel and HIV antibody test 
X 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
Serum Pregnancy test (hCG)  
X 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
 
 
 
 
 
X 
X 
X 
 
CV Telemetry (n) 
 
 
X 
X 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
X 
 
PGx DNA sample collection (i) 
 
 
X 
 
 
 
 
 
 
PGx RNA collection (j) 
 
 
X 
 
 
 
 
 
 
PK blood collection (k) 
 
 
X 
X 
X 
X 
 
X 
 
Study drug dosing 
 
 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 


CVN766 
 
Study No. CVN766-101 
Page 74 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
PGx=pharmacogenomic. 
(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must 
then be brought back to the clinic for re-evaluation per the investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose 
[within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at 
Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood 
pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, 
Day 8, Early Termination (if applicable), and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional 
tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to enable additional, retrospective analyses as 
needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and 
then every 12 hours until 48 hours post-dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample (6 mL) will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) 2.5 mL whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be 
collected during the food effect period. 
(k) Blood samples (6 mL) for PK analyses will be collected at time points indicated in Table 7. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry to telemetry should be recorded at 12 hours prior to dosing, and up to 24 hours after dosing 
 
 
 
 


CVN766 
 
Study No. CVN766-101 
Page 75 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
Cohort 3 SAD 
 Fasted-Fed Crossover 
 
Screening 
Dosing and 
Observation  
Inpatient 
D/C 
 
Inpatient 
No sooner than +14 days or 4 
half-lives of Day 8 visit 
 
 
+4 days 
post 
D/C 
E/T 
Follow-up 
Study Day:  
Days -28 
to -2  
Day 
-1  
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
8 
Day 
-1 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 14 (±2) (b) 
Informed consent 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Admitted to the Clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Abbreviated Neuro Exam 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination  
X 
X 
 
 
 
X  
X 
X 
 
 
 
X  
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight, height, and BMI (d) 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
 
Urine drug & cotinine screen 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Concomitant medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical conditions 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Clinical laboratory tests (f) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Hepatitis panel and HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy test (hCG)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
 
 
 
 
 
X 
X 
 
 
 
 
X 
X 
X 
 
CV Telemetry (n) 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
PGx DNA sample collection (i) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PGx RNA collection (j) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PK blood collection (k) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 
Lumbar puncture & CSF collection (k) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 


CVN766 
 
Study No. CVN766-101 
Page 76 of 81
Clinical Protocol – FINAL Version 1.0 
September 2021
 
CONFIDENTIAL 
*S3 Cohort will return no sooner than Day 14 or 4 half-lives (whichever is greater) after Day 8 for the Fed portion. The Fed portion will commence on Day -1 
will all the same schedule of events with the exception of dosing will be post-meal.  
  
PGx=pharmacogenomic. 
(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must 
then be brought back to the clinic for re-evaluation per the investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose 
[within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at 
Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood 
pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, 
Day 8, Early Termination (if applicable), and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional 
tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to enable additional, retrospective analyses as 
needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and 
then every 12 hours until 48 hours post-dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample (6 mL) will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) 2.5 mL whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be 
collected during the food effect period. 
(k) Blood samples (6 mL) for PK analyses will be collected at time points indicated in Table 7. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry to telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
 
Standardized pre-dose meal  
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Study drug dosing 
 
 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discharged from Clinic 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 


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CVN766 
 
Study No. CVN766-101 
Page 78 of 81
Clinical Protocol – Final Version 1.0 
September 2021
 
CONFIDENTIAL 
Multiple-Dose 
Regimen Cohorts 
SCR 
 
Check
-in 
 
Inpatient 
Dosing & Observation 
 
Inpatient 
Discharge 
(a) 
 
Outpatient Visit 
E/T 
Follow-up 
 
Study Day:  
Days 
-28 to -
2  
Day -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day  
5 
 (model for 
additional 
dosing days) 
Day  
6 
Day of 
last dose 
(e.g. Day  
7) 
1 day after 
last dose 
(e.g. Day 8) 
2 days after 
last dose 
(e.g. Day  
9) 
3 days ±0 
after last 
dose (e.g. 
Day 10) 
(o) 
7 days ±1 
after last 
dose (e.g. 
Day  
14) 
 
14 days ±2 after 
last dose (e.g. 
Day 21 ±2) (b) 
PGx DNA sample 
collection (i) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PGx RNA collection 
(j) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PK blood collection 
(k) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Lumbar puncture & 
CSF collection (k) 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Study drug dosing 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


CVN766 
 
Study No. CVN766-101 
Page 79 of 81
Clinical Protocol  - Final  Version 1.0 
September 2021
 
CONFIDENTIAL 
PGx=pharmacogenomic. 
(a) Events listed as occurring at “Inpatient Discharge” visit will occur on that day prior to formal “Inpatient Discharge” but not necessarily at the time of 
Discharge. 
(b) The Follow-up Visit will occur by telephone on Day 21 (±2) unless abnormal CS findings were observed upon discharge. In these cases, subjects must then 
be brought back to the clinic for re-evaluation per Investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 and Day 7 
(pre-dose [within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), Days 2 through 6 (pre-dose and 12 hours post-dose), 
Day 8, Day 9, Early Termination (if applicable), and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood pressure and 
heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Days 1 through 8, Day 9, 
Early Termination (if applicable), and as appropriate at the Follow-up Visit Day 21 (±2 days). Hormone laboratory tests (PRL, thyrotropin [TSH], and FT4) will 
be collected on Days 1 and 7 (morning [fasting] and 3 hours after dosing), Day 9, and Day 14 under fasted conditions. Fasting lipase tests will be collected at 
Day -1, Days 2, 7, and 8 (pre-dose). An additional tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to 
enable additional, retrospective analyses as needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Screening, Inpatient Check-in (Day -1), Days 1 and 7 (pre-dose [within 1 hour prior to dosing], and at 
0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), Days 2 through 6 (pre-dose and 12 hours post-dose), Days 8 and 9, Early Termination (if applicable), and as 
appropriate at the Follow-up Visit Day 21 (±2 days). 
(i) One blood sample (6 mL) will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) 2.5 mL whole blood samples will be collected on Day 1 and Day 7 (pre-dose, 8- and 24-hours post-dose) for RNA pharmacogenomic analysis.  
(k) Blood samples (6 mL) for PK analyses will be collected at time points indicated in Table 8.  CSF samples (up to 10 mL) will be collected at 3 h post-dose by 
lumbar puncture only in cohorts M1 and M2, as indicated in Table 10. Cohort M3 also may, at SRG discretion, undergo PK sampling from CSF, the choice of 
day and sampling time to be decided by SRG. 
(l) PTEs will be collected from signing of ICF up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) 24-hour urine collection is only done for cohort M1, predose and over 24 hours 
(o) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the Day 10 visit is not necessary. 
 
 


CVN766 
 
Study No. CVN766-101 
Page 80 of 81
Clinical Protocol  - Final  Version 1.0 
September 2021
 
CONFIDENTIAL 
Appendix B Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations.  
The Investigator agrees to assume the following responsibilities. 
1. Conduct the study in accordance with the protocol. 
2. Personally conduct or supervise the staff who will assist in the protocol. 
3. Ensure that study-related procedures, including study-specific (non-routine/nonstandard 
panel) screening assessments, are NOT performed on potential subjects prior to the receipt of 
written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed 
of these obligations. 
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conforms 
to local regulatory requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity and 
all anticipated risks to subjects. Make at least yearly reports on the progress of the study to 
the IRB/IEC and issue a final report within 3 months of study completion. 
7. Ensure that requirements for informed consent, as outlined in local regulations, are met. 
8. Obtain valid ICF from each subject who participates in the study and document the date of 
consent in the subject’s medical chart. Valid informed consent is the most current version 
approved by the IRB/IEC. Each ICF should contain a subject authorization section that 
describes the uses and disclosures of a subject’s personal information (including personal 
health information) that will take place in connection with the study. If an ICF does not 
include such a subject authorization, then the Investigator must obtain a separate subject 
authorization form from each subject or the subject’s legally acceptable representative. 
9. Prepare and maintain adequate case histories of all persons entering into the study, including 
eCRFs, hospital records, laboratory results, etc., and maintain these data for a minimum of 
2 years following notification by the sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The Investigator should 
contact and receive written approval from the sponsor before disposing of any such 
documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor.  
12. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours. 


CVN766 
 
Study No. CVN766-101 
Page 81 of 81
Clinical Protocol – Final Version 1.0 
September 2021
 
CONFIDENTIAL 
Appendix C Investigator Consent to Use of Personal Information  
Cerevance will collect and retain personal information of Investigator, including his or her name, 
address, and other personally identifiable information. In addition, Investigator’s personal 
information may be transferred to other parties located in countries throughout the world (e.g., 
the United Kingdom, United States, and Japan), including the following: 
• Cerevance, its affiliates, and licensing partners 
• Business partners assisting Cerevance, its affiliates, and licensing partners 
• Regulatory agencies and other health authorities 
• IRBs and IECs 
• Investigator’s personal information may be retained, processed, and transferred by Cerevance 
and these other parties for research purposes, including the following: 
• Assessment of the suitability of Investigator for the study and/or other clinical studies 
• Management, monitoring, inspection, and audit of the study 
• Analysis, review, and verification of the study results 
• Safety reporting and pharmacovigilance relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may 
contain the same chemical compound present in the study medication 
• Inspections and investigations by regulatory authorities relating to the study 
• Self-inspection and internal audit within Cerevance, its affiliates, and licensing partners 
• Archiving and audit of study records 
• Posting Investigator site contact information, study details, and results on publicly accessible 
clinical trial registries, databases, and websites 
• Investigator’s personal information may be transferred to other countries that do not have 
data protection laws that offer the same level of protection as data protection laws in the 
Investigator’s own country. 
• Investigator acknowledges and consents to the use of his or her personal information by 
Cerevance and other parties for the purposes described above. 
 


CVN766 
 
Study No. CVN766-101 
Page 1 of 79
Clinical Protocol  - Final  Version 2.0 
October  2021
 
CONFIDENTIAL 
 
 
 
 
PROTOCOL 
 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, 
Tolerability, and Pharmacokinetic Study of Escalating Single and 
Multiple Doses of CVN766  
in Healthy Subjects  
 
 
 
Short Title: Phase 1 SAD/MAD Study of CVN766 
 
Sponsor: 
Cerevance Gamma, Inc. 
One Marina Park Drive, Suite 1410 
Boston, MA 02210 
 
Study Number: 
CVN766-101 
IND Number: 
Not Applicable 
EudraCT Number: 
Not Applicable 
Compound: 
CVN766 
Protocol Version:  
2.0 
Date: 
21 October 2021 
 
 
 
CONFIDENTIAL PROPERTY OF CEREVANCE 
This document is a confidential communication of Cerevance Gamma, Inc. (“Cerevance”). Acceptance of this 
document constitutes the agreement by the recipient that no information contained herein will be published or 
disclosed without written authorization from Cerevance except to the extent necessary to obtain informed consent 
from those persons to whom the drug may be administered. Furthermore, the information is only meant for review 
and compliance by the recipient, his or her staff, and applicable institutional review committee and regulatory 
agencies to enable the conduct of the study. 


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CVN766 
 
Study No. CVN766-101 
Page 4 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
INVESTIGATOR AGREEMENT  
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, and 
any other product information provided by the sponsor. I agree to conduct this study in 
accordance with the requirements of this protocol and also to protect the rights, safety, privacy, 
and well-being of study subjects in accordance with the following: 
• The ethical principles that have their origin in the Declaration of Helsinki 
• International Council on Harmonisation, E6 GCP: Consolidated Guideline 
• All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations 
• Regulatory requirements for reporting serious adverse events (SAEs) defined in Section 9.9 
of this protocol 
• Terms outlined in the Clinical Study Site Agreement 
• Appendix B – Responsibilities of the Investigator 
 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix C of this protocol. 
Signature of Investigator 
Date 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State/Provence) 
Location of Facility (Country) 
 


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CVN766 
 
Study No. CVN766-101 
Page 6 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
8.1 
Study Medication and Materials ............................................................................... 32 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling ..................................... 32 
8.1.2 Drug Storage ...................................................................................................... 33 
8.1.3 Dose and Regimen ............................................................................................. 33 
8.1.4 Overdose ............................................................................................................ 34 
8.2 
Investigational Drug Assignment and Dispensing Procedures .................................. 35 
8.3 
Randomization Code Creation and Storage .............................................................. 35 
8.4 
Investigational Drug Blind Maintenance .................................................................. 35 
8.5 
Unblinding Procedure .............................................................................................. 35 
8.6 
Accountability and Destruction of Sponsor-Supplied Drugs ..................................... 36 
9.0 
STUDY PLAN .............................................................................................................. 37 
9.1 
Study Procedures ..................................................................................................... 37 
9.1.1 Informed Consent Procedure .............................................................................. 37 
9.1.2 Demographics, Medical History, and Medication History Procedure .................. 37 
9.1.3 Physical Examination Procedure ........................................................................ 37 
9.1.4 Weight, Height, and BMI ................................................................................... 38 
9.1.5 Vital Sign Procedure .......................................................................................... 38 
9.1.6 Documentation of Concomitant Medications ...................................................... 38 
9.1.7 Documentation of Concurrent Medical Conditions ............................................. 39 
9.1.8 ECG Procedure .................................................................................................. 39 
9.1.9 Pharmacogenomic Sample Collection ................................................................ 39 
9.1.10 PK Sample Collection ........................................................................................ 41 
9.1.11 PK Parameters ................................................................................................... 43 
9.1.12 Procedures for Clinical Laboratory Samples ....................................................... 43 
9.1.13 Contraception and Pregnancy Avoidance Procedure ........................................... 45 
9.1.14 Pregnancy .......................................................................................................... 46 
9.1.15 Documentation of Screen Failure ....................................................................... 46 
9.1.16 Documentation of Randomization ...................................................................... 47 
9.2 
Monitoring Subject Treatment Compliance .............................................................. 47 
9.3 
Schedule of Observations and Procedures ................................................................ 47 
9.3.1 Screening ........................................................................................................... 47 
9.3.2 Inpatient Check-In ............................................................................................. 47 
9.3.3 Final Visit (discharge day from clinic) ............................................................... 48 
9.3.4 Early Termination .............................................................................................. 48 
9.3.5 Follow-up Visit .................................................................................................. 48 
9.4 
Biological Sample Retention and Destruction .......................................................... 48 
9.5 
Blood Volume ......................................................................................................... 49 
9.6 
CSF Volume ............................................................................................................ 49 


CVN766 
 
Study No. CVN766-101 
Page 7 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
9.7 
Definitions ............................................................................................................... 49 
9.7.1 PTE.................................................................................................................... 49 
9.7.2 AE ..................................................................................................................... 49 
9.7.3 Additional Points to Consider for PTEs and AEs ................................................ 49 
9.7.4 SAEs .................................................................................................................. 51 
9.7.5 Severity of PTEs and AEs .................................................................................. 52 
9.7.6 Causality of AEs ................................................................................................ 52 
9.7.7 Relationship to Study Procedures ....................................................................... 52 
9.7.8 Start Date ........................................................................................................... 52 
9.7.9 Stop Date ........................................................................................................... 53 
9.7.10 Frequency .......................................................................................................... 53 
9.7.11 Action Concerning Study Medication ................................................................. 53 
9.7.12 Outcome ............................................................................................................ 53 
9.8 
Procedures ............................................................................................................... 54 
9.8.1 Collection and Reporting of AEs ........................................................................ 54 
9.8.2 Collection and Reporting of SAEs ...................................................................... 55 
9.8.3 Reporting of Abnormal LFT .............................................................................. 55 
9.9 
Follow-up of SAEs .................................................................................................. 55 
9.9.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities ..... 56 
10.0 
STUDY-SPECIFIC COMMITTEES ............................................................................. 57 
11.0 
DATA HANDLING AND RECORDKEEPING ............................................................ 58 
11.1 
CRFs (Electronic) .................................................................................................... 58 
11.2 
Record Retention ..................................................................................................... 58 
12.0 
STATISTICAL METHODS .......................................................................................... 60 
12.1 
Statistical and Analytical Plans ................................................................................ 60 
12.1.1 Analysis Sets...................................................................................................... 60 
12.1.2 Analysis of Demographics and Other Baseline Characteristics ........................... 60 
12.1.3 PK Analysis ....................................................................................................... 60 
12.1.4 Safety Analysis .................................................................................................. 61 
12.2 
Interim Analysis and Criteria for Early Termination ................................................ 61 
12.3 
Determination of Sample Size .................................................................................. 62 
13.0 
QUALITY CONTROL AND QUALITY ASSURANCE............................................... 63 
13.1 
Study-Site Monitoring Visits ................................................................................... 63 
13.2 
Protocol Deviations.................................................................................................. 63 
13.3 
Quality Assurance Audits and Regulatory Agency Inspections ................................ 64 
14.0 
ETHICAL ASPECTS OF THE STUDY ........................................................................ 65 
14.1 
IRB and/or IEC Approval ........................................................................................ 65 
14.2 
Subject Information, Informed Consent, and Subject Authorization ......................... 66 


CVN766 
 
Study No. CVN766-101 
Page 8 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
14.3 
Subject Confidentiality ............................................................................................ 67 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy ................................. 67 
14.4.1 Publication and Disclosure ................................................................................. 67 
14.4.2 Clinical Trial Registration .................................................................................. 68 
14.4.3 Clinical Trial Results Disclosure ........................................................................ 68 
14.5 
Insurance and Compensation for Injury .................................................................... 68 
15.0 
REFERENCES .............................................................................................................. 69 
 
LIST OF IN-TEXT TABLES 
Table 1 
Single-Dose Visit Schedule ................................................................................ 21 
Table 2 
Multiple Dose Visit Schedule ............................................................................. 22 
Table 3 
Prohibited Medications and Dietary Products ..................................................... 29 
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo ...................... 32 
Table 5 
Planned Single and Multiple Dose Levels by Cohort .......................................... 34 
Table 6 
Collection of Blood Samples for PK Analysis in Single-Dose Cohorts ............... 41 
Table 7 
Collection of Blood Samples for PK Analysis in Multiple-Dose Cohorts ............ 41 
Table 8 
Collection of CSF Samples for PK Analysis in Single-Dose Cohorts .................. 42 
Table 9 
Collection of CSF Samples for PK Analysis in Multiple Dose Cohorts .............. 42 
Table 10 
Clinical Laboratory Tests ................................................................................... 43 
Table 11 
Medically Significant AE List (categorized as Serious Adverse Events) ............. 52 
Table 12 
Windows for PK Blood Sample Collection ........................................................ 63 
 
LIST OF IN-TEXT FIGURES 
Figure 1 
CVN766-101 Study Schematic........................................................................... 20 
LIST OF APPENDICES 
Appendix A 
Schedule of Study Procedures ............................................................................ 70 
Appendix B 
Responsibilities of the Investigator ..................................................................... 78 
Appendix C 
Investigator Consent to Use of Personal Information .......................................... 79 
 


CVN766 
 
Study No. CVN766-101 
Page 9 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
2.0 
STUDY SUMMARY 
Name of Sponsor(s): 
Cerevance, Inc. 
Compound: 
Title of Protocol: A Phase 1, Randomized, Double-Blind, 
Placebo-Controlled, Safety, Tolerability, and 
Pharmacokinetic Study of Escalating Single and Multiple 
Doses of CVN766 in Healthy Subjects  
IND No.:  
EudraCT No.: 
Not Applicable 
Study Number: CVN766-101 
Phase: 1 
Study Design: 
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in 
healthy subjects with concurrent PK sampling from blood plasma, urine, and cerebrospinal fluid. The overall study 
design is outlined below: 
  
Part 1: Single-Dose Regimen and Fasted-Fed Crossover 
For the single-dose regimen, approximately 40 healthy male or female subjects will be enrolled in 1 of 5 single-dose 
cohorts (designated as S1 through S5, respectively) in an ascending fashion. Each cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a single oral dose of CVN766 suspension, and 
2 subjects will receive a matching placebo suspension under overnight fasted conditions. Subjects will remain fasted 
for 4 hours post-dose. Consumption of water is permitted as desired except for 1 hour before and after administration 
of Study Drug. Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in each 
cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 or placebo to the 
remainder of subjects within the cohort. After blinded review by the Safety Review Group (SRG) of 24-hour, post-
dose safety and tolerability data from the sentinel group, the remaining 6 subjects of each cohort may be dosed 
provided that the adverse event (AE) profile in the first 2 subjects is considered acceptable. To accommodate the 
lumbar puncture in the S3 fasted cohort, after the sentinel group, the remaining 6 subjects dosing may be staggered 
every two days. The planned dose levels will be 5, 15, 45, 125, and 250 mg CVN766.  The SRG will review all 
available blinded safety, tolerability, clinical laboratory results (minimally including samples collected from 
subjects through 72-hours post-dose), and pharmacokinetic (PK) data after each cohort and before subsequent dose 
escalation. Each following dose level may be higher, lower, or remain the same as the preceding cohort, dependent 
on the recommendation of the SRG.  
Additional cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety and tolerability 
of CVN766. For example, if cohort S5 is well-tolerated, additional cohorts with higher dose levels may be 
considered. Such additional cohorts will follow the same schedule of events as for cohorts S1 through S5. 
Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary to fully 
characterize the PK profile of CVN766. 
To assess the effect of food on CVN766 bioavailability in suspension formulation, the single-dose administration 


CVN766 
 
Study No. CVN766-101 
Page 10 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
will be repeated in a single cohort (S3) after ingestion of a standardized high-fat, high-calorie meal according to 
FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Dec 2002). Once the safety 
of the S3 cohort dose level has been assessed, the S3 cohort subjects will return to the clinic (no sooner than 14 days 
after their prior dose, or at least 4 half-lives, has lapsed based on preliminary PK data, whichever is longer). They 
will receive the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish the 
entire content of their breakfast within 25 minutes and will receive an investigational product 30 minutes (± 5 
minutes) after beginning the meal. Sentinel dosing will not be required for subjects returning to the clinic for the fed 
regimen. If the CVN766 PK parameters in the fasted S3 cohort reveal poor absorption with inconclusive results, the 
fed cohort will be deferred until a higher dose level.    
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit for safety and 
PK assessments. On Day 1, subjects will undergo safety monitoring and PK sampling from blood plasma through 
72 hours post-dose and, for cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. The total 
confinement period will be 4 nights, unless extended at the discretion of the Investigator, e.g., for monitoring and/or 
management of AEs. Follow-up assessments will occur on approximately Days 8 and 14 and +21 and +28 for cohort 
S3. 
A summary of the single-dose regimen visit schedule is presented below:  
Screening a 
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b 
Inpatient PK,  
Safety and 
Lumbar 
Puncture Site 
Assessments 
(S3 fasted) 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
 
Day -28 to -2 
Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14 
±2 days 
 
(a) Screening will occur at study entry. S3 subjects returning for the “Fed” repetition of the single-dose 
regimen will not undergo Screening assessments except as required at Day -1. 
(b) CSF collection will apply only to cohort S3 (fasted). 
(c) Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs. 
(d) The final follow-up assessment will occur by telephone unless abnormal, clinically significant (CS) 
findings were observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
 
Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 healthy male and female subjects age 18 to 50 years old will be 
enrolled in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. 
The dose levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-
dose cohorts M1 through M3, respectively. Each multiple-dose cohort will consist of 8 subjects randomized to 
CVN766 or placebo, whereby 6 subjects will receive a daily oral dose of CVN766, and 2 subjects will receive a 
matching placebo for 7 days. Dosing will be administered in the fasting state; this can be changed by the SRG if 
exposure is found to be higher in the fed state. The planned dosing duration for the multiple-dose cohorts is 7 days. 
However, the duration may be increased to ≤14 days at the discretion of the SRG if preliminary PK data suggest 
steady-state will not be achieved within 6 days of daily dosing. For each dose on intensive PK sampling days (first 
and last days of dosing, e.g., Days 1 and 7), subjects will remain fasted for 4 hours post-dose. On other dosing days 
(Days 2-6), subjects will remain fasted for 1-hour post-dose. Consumption of water is permitted as desired except 
for 1 hour before and after administration of Study Drug. Unlike the single-dose regimen, sentinel dosing within 
cohorts is not required in the multiple-dose regimen. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all safety, tolerability, and 
clinical laboratory results for the fasting drug administration to single-dose Cohort S3 (minimally including samples 
collected through Day 4) and available PK data. For each multiple-dose cohort after the first, the actual choice of 
dose level may be modified by the SRG after the available blinded safety, tolerability, clinical laboratory results, 


CVN766 
 
Study No. CVN766-101 
Page 11 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
and PK data in the preceding multiple-dose and corresponding single-dose cohorts (i.e., multiple-dose Cohort M2 
will not initiate until the data review for multiple-dose Cohort M1 and single-dose cohort S4 is complete). Each 
subsequent dose level may be higher, lower, or remain the same as the preceding. 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety 
and tolerability of CVN766. Such additional cohorts will follow the same schedule of events as for prior multiple-
dose cohorts.  Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary 
to fully characterize the PK profile of CVN766. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit 
for the duration of the dosing period and for at least 48 hours after the last dose for safety and PK assessments before 
discharge. On treatment Days 1 and 7, subjects will undergo safety monitoring and PK sampling from blood plasma 
through 48 hours post-dose and, in cohort M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, 
on treatment Day 7 (or last day of dosing, if extended beyond Day 7), subjects will additionally undergo PK sampling 
from CSF via lumbar puncture at 3 hours post-dose. If needed to resolve questions arising from prior cohorts’ data, 
subjects in cohort M3 also may, at SRG discretion, undergo PK sampling from CSF via lumbar puncture, the choice 
of day (e.g., Day 1 or Day 7) and sampling time to be decided by SRG. Subjects in MAD cohorts may be asked to 
return to the clinic for an additional PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK 
data, i.e., t½). The total confinement period will be 9 nights unless extended for additional dosing days or 
management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final dose. 
A summary of the multiple-dose regimen visit schedule is presented below: 
Screening 
Inpatient  
Check-in 
Dosing, PK, 
CSF, & Safety 
Assessments  a 
PK / Safety 
Assessments & 
inpatient 
discharge b 
Follow-Up Outpatient 
Visits c 
Follow-Up Call d 
Day -28 to -2 
Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g., 
Days 8-9) 
3 days ±0 after last dose 
(e.g., Day 10) & 
7 days ± 1 after last dose 
(e.g., Day 14) 
14 days ±2 after last 
dose (e.g., Day 21) 
(a) CSF sampling will occur on Day 7 in cohorts M1 and M2. Cohort M3 also may, at SRG discretion, undergo 
PK sampling from CSF, the choice of day and sampling time to be decided by SRG.  
(b) Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or, if 
necessary, to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after last dose (e.g., Day 
10) may be omitted at Investigator’s discretion. 
(d) The Follow-up Visit will occur by telephone unless abnormal, clinically significant (CS) findings are 
observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to ≤14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in cohort M1. 
Safety Review Group (SRG) 
The SRG will be comprised of the Investigator, Medical Monitor, Cerevance Responsible Medical Officer and may 
include other Cerevance representatives. A pharmacokineticist and other subject matter experts may participate as 
needed. The SRG will be responsible for ongoing review of safety, tolerability, and clinical laboratory results, and 
available PK data and deciding: 
1. Expand each single-dose cohort from the sentinel cohort to the entire cohort (based on a review of at least 
24 hours post-dose safety data from each of the sentinel subjects), 
2. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in single-
dose cohorts (based on a review of available data including at least 72 hours post-dose safety data and 
clinical laboratory results from each of the subjects in the current cohort),  
3. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in 
multiple-dose cohorts (based on a review of available data including at least 48 hours post 7th dose safety 


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CVN766 
 
Study No. CVN766-101 
Page 13 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
Main Criteria for Exclusion: 
Subjects have a known hypersensitivity to any component of the formulation of CVN766. Subjects have evidence 
of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, 
urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, psychiatric disorder, or other 
abnormality that may impact the ability of the subject to participate or potentially confound the study results. Any 
finding in the subject’s medical history, physical examination, or safety laboratory tests gives reasonable suspicion 
of a condition that might interfere with the conduct or interpretation of the study.  
A complete list of exclusion criteria is provided in Section 7.2.  
In addition, subjects may not use any excluded medications (including oral contraceptives as listed in Table 3), 
supplements, or food products. Concomitant medications and dietary products to be excluded are listed in Table 3. 
Main Criteria for Evaluation and Analyses: 
- Safety:  
Safety parameters will include AEs, clinical laboratory results, vital signs, physical examinations, electrocardiogram 
(ECG). AEs will be collected from signing the informed consent form (ICF) up until dosing on Day 1 as pretreatment 
events (PTEs), and any event that occurs from dosing until 14 days after the last dose will be captured as an AE. 
Vital signs will be recorded at Screening, Inpatient Check-in (Day -1), and throughout the dosing period. Vital signs 
will include tympanic body temperature measurement, blood pressure, respiration rate, and pulse (beats per minute 
[bpm]). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day 
-1) 15 minutes apart. Heart rate and blood pressure will be measured after at least 5 minutes supine and again at 2 
minutes after standing for all scheduled timepoints.  
Standard 12-lead ECGs will be recorded at Screening, Inpatient Check-in (Day -1), and periodically throughout the 
dosing period. Triplicate ECGs will be taken at each timepoint. 
A complete list of safety assessments is provided in Section 9.1, and the full Schedule of Study Procedures is 
provided in Appendix A. 
- PK:  
The plasma PK parameters are used as PK endpoints to determine drug exposure at each dose and facilitate dose 
escalations.  
Plasma samples will be collected for the determination of concentrations of CVN766 throughout the study as 
prescribed in the Schedule of Study Procedures (Appendix A). Cerebrospinal fluid (CSF) samples will be collected 
for the determination of concentrations of CVN766 as described in Section 9.6 and the Schedule of Study Procedures 
(Appendix A). PK sampling timepoints may be modified or added based on emerging PK data to most appropriately 
characterize the PK profile of CVN766 as determined by the SRG. 
PK parameters of CVN766 will be derived using noncompartmental analysis methods from the concentration-time 
data for all evaluable subjects. Actual sampling times, rather than scheduled sampling times, will be used in all 
computations involving sampling times. The following PK parameters will be determined from concentrations of 
CVN766 in plasma: Cmax, AUC from time 0 to the last quantifiable concentration (AUCt), AUC from time 0 to 
infinity (AUC∞), AUC from time 0 to 24 hours (AUC24), time to reach Cmax (tmax), terminal elimination rate constant 
(λz), terminal elimination half-life (t1/2z), apparent clearance (CL/F), and apparent volume of distribution (Vz/F). 
Multiple-dose PK will also include AUC over the dosing interval (AUCtau), apparent clearance at steady state 
(CL/Fss), apparent volume of distribution at steady state (Vz/Fss), steady-state nadir concentrations, and 
accumulation ratios  
The PK parameters to be determined from concentrations of CVN766 in CSF will include plasma: CSF ratio 
by time point. - Pharmacogenomics: 
One 6 mL whole blood sample will be collected at pre-dose on Day 1 for pharmacogenomic analysis; this will only 
be collected once per subject. Two 2.5 mL whole blood samples will be collected at pre-dose on Day 1 and at 
multiple timepoints post-dose for ribonucleic acid (RNA) pharmacogenomic analysis. The pre-dose RNA blood 
samples should be collected under fasted conditions and prior to any other blood collection. The samples will be 
stored for no longer than 15 years after completion of the CVN766 study and/or until the drug development of 
CVN766 is no longer actively pursued by Cerevance or its collaborators. No samples will be stored for longer than 
permitted by the applicable law, and samples will be destroyed upon notification from Cerevance. “Stored samples” 
in this context are defined as samples that are double coded (the samples are stripped of all personal identifying 


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CVN766 
 
Study No. CVN766-101 
Page 16 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRSD 
maximum recommended starting dose 
NCS 
not clinically significant 
NOAEL 
no-observed-adverse-effect-level 
Ox1R 
orexin 1 receptor 
Ox2R 
orexin 2 receptor 
PK 
pharmacokinetic 
PRL 
prolactin 
PT 
preferred term 
PTE 
pretreatment event 
QTcB 
QT interval with Bazett’s correction method 
QTcF 
QT interval with Fridericia’s correction method 
RNA 
ribonucleic acid 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAD 
single-ascending dose 
SAP 
statistical analysis plan 
SOC 
system organ class 
SRG 
Safety Review Group 
SUSARs 
suspected unexpected serious adverse reactions 
t1/2z 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to reach Cmax 
ULN 
upper limit of normal 
Vz/F 
apparent volume of distribution after extravascular administration 
Vz/Fss 
apparent volume of distribution after extravascular administration at steady state 
WHO 
World Health Organization 


CVN766 
 
Study No. CVN766-101 
Page 17 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
4.0 
INTRODUCTION 
4.1 
Background 
The neuropeptide orexin, also known as hypocretin, is produced exclusively in the orexigenic 
neurons in the hypothalamus. There are two forms of orexin, Orexin-A and orexin-B that are 
alternatively spliced from the same gene, HCRT.   There are two orexin receptors, orexin 1 receptor 
(Ox1R) and orexin 2 receptors (Ox2R), both of which are G-protein coupled receptors. Both 
orexin-A and orexin-B can bind to either receptor and in each case, agonist binding results in an 
increase in intracellular calcium levels. However, while orexin-A is equipotent at both receptors, 
orexin-B shows a 10-fold selectivity for Ox2R.  
Ox1R is selectively expressed in key brain areas relating to psychiatric disorders. Ox1R-expressing 
neurons in the bed nucleus of the stria terminalis, amygdala, locus coeruleus, raphe nucleus, and 
the ventral tegmental area are important in regulating emotions of stress, anxiety, motivation, and 
reward. CVN766 is a potent and highly selective small-molecule Ox1R antagonist with no 
significant off-target activity. Nonclinical PK and toxicology studies with CVN766 and other 
Ox1R antagonists have established their pharmacological characteristics and probable safety 
profile. 
Ox2R is expressed in some overlapping areas, including the raphe nucleus, ventral tegmental area, 
but also areas important to arousal and sleep regulation, including the tuberomammillary nucleus. 
The widely used sleep aid suvorexant (Belsomra®), approved for use in Australia, is a dual Ox1R 
and Ox2R antagonist, but its sleep-inducing effects are generally attributed to its activity on Ox2R. 
A second dual Ox1R and Ox2R antagonist, lemborexant, appeared safe and effective in clinical 
studies, has been approved in many countries worldwide, and has been submitted for marketing 
authorization in Australia.  
Clinical effects to be expected of a selective Ox1R antagonist remain uncertain. CVN766 has not 
yet been studied in humans. Other selective Ox1R antagonists have reported early-stage human 
clinical trials, notably JNJ-61393215 (ClinicalTrials.gov Identifier: NCT04080752; Salvadore et 
al., 2020) and ACT-539313 (NCT01954589; Kaufmann et al., 2020; Kaufmann et al., 2021). Both 
drugs were well tolerated and deemed safe for investigational use, the most common AEs being 
somnolence and mild headache.   
4.2 
Rationale for the Proposed Study 
CVN766 is a highly selective orexin-1 receptor (Ox1R) antagonist and may have utility as 
treatment for psychiatric disorders including schizophrenia, panic disorder and anxiety, and 
addiction. Its safety and PK profile have been preliminarily established in nonclinical toxicology 
studies. The present study will be the first conducted in humans with CVN766 and will examine 
the compound's safety, tolerability, and PK in healthy subjects. 
Nonclinical pharmacology, toxicity, and pharmacokinetic (PK) studies support the proposed 
escalating single- and multiple-dose study of CVN766 in healthy subjects with a starting dose of 
5 mg. Section 6.2 outlines the justification for the planned dose ranges.  
 


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CVN766 
 
Study No. CVN766-101 
Page 20 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
6.0 
STUDY DESIGN AND DESCRIPTION 
6.1 
Study Design 
This is a phase 1, randomized, double-blind, placebo-controlled, single- and multi-dose ascending 
study in healthy subjects. Figure 1 provides a schematic illustration of the study. 
Figure 1 
CVN766-101 Study Schematic 
 
 
6.1.1 Part 1: Single-Dose Regimen and Fasted-Fed Crossover 
Approximately 40 subjects will be enrolled in 1 of the 5 single-dose cohorts (designated as S1 
through S5, respectively) in an ascending fashion. Dose escalation will only occur after a fully 
blinded review of all available safety, tolerability, clinical laboratory results (minimally including 
samples collected from subjects through 72-hours post-dose), and available PK data, including at 
least a 72-hour follow-up of the most recent cohort. 


CVN766 
 
Study No. CVN766-101 
Page 21 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
The planned dose levels are provided in Table 5. Each cohort will consist of 8 subjects randomized 
to CVN766 or placebo, whereby 6 subjects will receive a single dose of CVN766 and 2 subjects 
will receive a matching placebo under overnight fasted conditions.  
Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in 
each cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 
to the remainder of subjects within the cohort. After blinded review of 24-hour post-dose safety 
and tolerability data, the remaining 6 subjects of each cohort may be dosed provided that the 
adverse event (AE) profile of CVN766 in the first 2 subjects is considered acceptable.  
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the 
unit for safety and PK assessments at least 72 hours after dosing. On Day 1, subjects will undergo 
safety monitoring (including labs, physical exam, abbreviated neuro exam, cardia telemetry at 12-
hours pre-dose) and PK sampling from blood plasma through 72 hours post-dose.  In addition, for 
cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. For subjects 
participating in the SAD cohorts, the total confinement period will be 4 nights unless extended for 
management of AEs at the discretion of the Investigator. Follow-up assessments will occur on 
approximately Days 8 and 14. 
To assess the effect of food on bioavailability of CVN766 in suspension formulation, single-dose 
administration will be repeated in a single cohort after ingestion of a standardized high-fat high-
calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed 
bioequivalence studies, Dec 2002). Once the safety of the S3 cohort dose level has been assessed, 
the S3 cohort subjects will return to the clinic (no sooner than 14 days after their prior dose, or at 
least 4 half-lives has lapsed based on preliminary PK data, whichever is longer) and will receive 
the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish 
the entire content of their breakfast within 25 minutes and will receive an investigational product 
30 minutes (± 5 minutes) after beginning the meal. Sentinel dosing will not be required for subjects 
returning to the clinic for the fed regimen.  If the CVN766 PK parameters in the fasted S3 cohort 
reveal poor absorption with inconclusive results, the fed cohort will be deferred until a higher dose 
level. 
An outline of the single-dose study visit schedule is included in Table 1. A Schedule of Study 
Procedures is listed in Appendix A. 
Table 1 
Single-Dose Visit Schedule 
Screening a 
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b 
Inpatient PK 
& 
Safety 
Assessments 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
Day -28 to -2 Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14  
±2 days 
(a) Screening will occur at study entry. Subjects returning for the “Fed” repetition of the single-dose regimen 
will not undergo Screening assessments except as required at Day -1. 
(b) CSF collection will apply only to cohort S3 (fasted). 
(c) Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs. 
(d) The final follow-up assessment will occur by telephone unless abnormal CS findings are observed upon 
discharge. In these cases, subjects must return to the clinic for re-evaluation. 


CVN766 
 
Study No. CVN766-101 
Page 22 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
6.1.2 Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 subjects will be enrolled in 1 of the 3 multiple-
dose cohorts (designated as M1 through M3, respectively) in an ascending fashion.  Dosing will 
be administered in the fasting state; this can be changed by the SRG if exposure is found to be 
higher in the fed state. The dose levels planned to be studied in the multiple-dose regimen (M1 
through M3) are provided in Table 5. Each multiple-dose cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a daily dose of CVN766, and 
2 subjects will receive matching placebo for 7 days. However, the duration may be increased to 
≤14 days at the discretion of the safety review group (SRG) if preliminary PK data suggest steady-
state will not be achieved within 6 days of daily dosing. Unlike the single-dose regimen, sentinel 
dosing within cohorts is not required in the multiple-dose regimen. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and 
remain in the unit for the duration of the dosing period and for at least 48 hours after the last dose 
for safety and PK assessments before discharge. On treatment Days 1 and 7, subjects will undergo 
safety monitoring and PK sampling from blood plasma through 48 hours post-dose and, in cohort 
M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, on treatment Day 7 (or 
last day of dosing, if extended beyond Day 7), subjects will additionally undergo PK sampling 
from CSF via lumbar puncture at 3 hours post-dose. If needed to resolve questions arising from 
prior cohorts’ data, subjects in cohort M3 also may, at SRG discretion, undergo PK sampling from 
CSF via lumbar puncture, the choice of day (e.g., Day 1 or Day 7) and sampling time to be decided 
by SRG. Subjects in MAD cohorts may be asked to return to the clinic for an additional plasma 
PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK data, i.e., t½. The 
total confinement period will be 9 nights unless extended for additional dosing days or for 
management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final 
dose. A summary of multiple-dose study visits is included in Appendix A.  
Table 2 
Multiple Dose Visit Schedule 
Screening 
Inpatient  
Check-in 
Dosing, 
PK, 
CSF, & Safety 
Assessments  a,f 
PK 
/ 
Safety 
Assessments 
& 
inpatient discharge b 
Follow-Up 
Outpatient 
Visits c 
Follow-Up Call d 
Day -28 to -2 Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g. Days 
8-9) 
3 days ±0 after last dose 
(e.g. Day 10) &  
7 days ± 1 after last dose 
(e.g. Day 14) 
14 days ±2 after 
last 
dose 
(e.g. 
Day 21) 
(a) CSF sampling will occur on Day 7 in cohorts M1 and M2. Cohort M3 also may, at SRG discretion, undergo 
PK sampling from CSF, the choice of day and sampling time to be decided by SRG. 
(b) Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or if necessary, 
to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after the last dose (e.g., 
Day 10) may be omitted at Investigator’s discretion. 
(d) The Follow-up Visit will occur by telephone unless abnormal CS findings are observed upon discharge. In 
these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to ≤14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in cohort M1. 


CVN766 
 
Study No. CVN766-101 
Page 23 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
6.1.3 Dose Escalation  
The SRG will be comprised of the Investigator, Medical Monitor, Cerevance Responsible Medical 
Officer and may include other Cerevance representatives. A pharmacokineticist and other subject 
matter experts may participate as needed. The SRG will be responsible for ongoing review of 
safety, tolerability, clinical laboratory results, and available PK data and deciding to: 
• Expand each single-dose cohort from the sentinel cohort to the full cohort (based on a 
review of at least 24 hours post-dose safety data from each of the sentinel subjects), 
• Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in single-dose cohorts (based on a review of available data including at least 72 
hours post-dose safety data and clinical laboratory results from each of the subjects in the 
current cohort),  
• Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in multiple-dose cohorts (based on a review of available data including at least 48 
hours post 7th dose safety data from each of the subjects in the current cohort), 
• Add additional dose cohort(s) in either the single- or multiple-dose studies, 
• Increase the duration of dosing in the multiple-dose cohorts from 7 days to ≤14 days 
If 2 or more subjects in a single cohort experience the same type of serious or medically adverse 
event, further dosing will be withheld until the SRG investigates the events.  Based on this 
assessment, the SRG will determine if the study should be terminated or continued and whether 
modification of planned dose levels and/or implementation of additional safety monitoring is 
indicated.   
For each cohort (including sentinel subjects, where applicable), the SRG will carefully review the 
available blinded safety, tolerability, clinical laboratory results, and PK data to determine whether 
dosing should stop or continue (and, if continued, at what dose, including whether to repeat the 
previous dose), whether additional sequential dosing should be implemented in future cohorts or 
whether the blind should be broken to identify whether the subjects received CVN766 or placebo. 
However, precautions must be taken not to unblind the study staff, including the investigator. 
If all doses are tolerated, then additional cohorts with higher doses may be considered; The actual 
choice of the subsequent dose level will occur after the full review of the available blinded safety, 
tolerability, clinical laboratory results, and available PK data in the preceding cohort. The 
subsequent dose level may be higher, lower, or remain the same as the preceding dose level. If 
necessary, additional cohort(s) may be added to fully characterize the safety and tolerability of 
CVN766. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all available 
safety, tolerability, and clinical laboratory results for the fasting drug administration to single-dose 
Cohort S3 (minimally including samples collected through Day 4) and available PK data. For each 
multiple-dose cohort after the first, the actual choice of dose level may be modified by the SRG 
after review of the available blinded safety, tolerability, and clinical laboratory results and PK data 
in the preceding multiple-dose and next-higher-dosage single-dose cohorts (i.e., multiple-dose 
Cohort M2 will not initiate until the data review for multiple-dose Cohort M1 and single-dose 


CVN766 
 
Study No. CVN766-101 
Page 24 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
cohort S4 is complete). Each subsequent dose level may be higher, lower, or remain the same as 
the preceding dose level. 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully 
characterize the safety and tolerability of CVN766. Such additional cohorts will follow the same 
schedule of events as for prior multiple-dose cohorts. Additional/Alternative PK timepoints may 
be implemented if the SRG determines this is necessary to fully characterize the PK profile of 
CVN766. 
All AEs reported during the Treatment Period, both within and across cohorts, up to the time of 
discharge, will be evaluated to assess the need for the subject and/or study termination in 
accordance with the prespecified criteria for discontinuation/termination (Section 6.3.1).  
Additionally, the SRG may decide not to escalate the dose for a particular cohort but rather 
administer the same or a lower dose level to the next cohort. Additional/ Alternative PK timepoints 
may be implemented if the SRG determines this is necessary to fully characterize the PK profile 
of CVN766. 
6.2 
Justification for Study Design, Dose, and Endpoints 
The study is double-blind and placebo-controlled to avoid subjective bias in the assessment of the 
safety and tolerability of CVN766. Dose escalation will be predicated on a review of available 
blinded safety, tolerability, and PK data observations for each prior dose cohort.  
The sponsor has selected the starting dose level considering the FDA Guidance for Industry 
(Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult 
Healthy Volunteers, 06 July 2005) and providing additional safety factors to the initial calculations 
based on the principles outlined in the guidance. The toxicity profile of CVN766 after oral dosing 
was examined in repeat dosing studies in rats and dogs. Scaling based on body surface area was 
conducted by multiplying the NOAELs for the most sensitive animal species by the appropriate 
conversion factors. Based on these calculations and applying a 10-fold safety margin below the 
NOAEL human-equivalent dose (HED), the maximum recommended starting dose (MRSD) for 
this first-in-human study is 167 mg for a 60 kg subject. The selected starting dose level is 5 mg. 
The study's multiple-ascending dose (MAD) portion seeks to prepare for subsequent repeat dosing 
studies in subjects. Each MAD dose level will have been studied or exceeded in the SAD portion 
of the study before its use in a MAD cohort.  
Nonclinical toxicity study data provide a basis for calculating the maximum exposure level that 
can be presumed safe. Escalating to the HED of the NOAEL in the most sensitive animal species, 
the maximum dose for clinical use is 1670 mg/day.  
The projected t1/2z in animal species ranged up to 6.5 hours, so sample collection through Inpatient 
Discharge 72 hours post-dose is expected to correspond to more than 5 half-lives and is anticipated 
to be adequate to document elimination of CVN766. The study design allows for collecting 
additional PK samples at later timepoints if preliminary emerging PK results are indicated.  
AEs, physical exams, vital signs, ECG findings, and clinical laboratory results are used as safety 
assessments to determine dose tolerability and dose-limiting effects of CVN766. The plasma PK 
and CSF parameters and PK endpoints will help elucidate the pharmacology of CVN766.  


CVN766 
 
Study No. CVN766-101 
Page 25 of 79
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CONFIDENTIAL 
Samples for DNA analysis will be collected and may be used to evaluate drug metabolic enzyme 
and transporter polymorphisms that may contribute to the variability in the PK of CVN766. 
6.3 
Premature Termination or Suspension of Study or Investigational Site 
6.3.1 Criteria for Premature Termination or Suspension of the Study 
The study will be completed as planned unless new information or other evaluation regarding the 
safety of the study medication indicates an adverse change in the risk profile for the compound, 
such that the SRG or Institutional Review Board (IRB) considers the risk is no longer acceptable 
for subjects participating in the study. 
In addition, if any of the following occur, further dosing will be withheld until the SRG reviews 
the relevant data, including unblinded data (if deemed necessary by the SRG request), and will 
decide whether it is safe to suspend dosing or continue dosing at either the planned or alternative 
dose levels or decides to prematurely terminate the study: 
1. Two or more subjects in any single cohort or across more than 1 cohort experience the same 
type of serious or Medically Significant event as defined by the Investigator 
2. Two or more subjects in any single cohort or across more than 1 cohort experience alanine 
aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations >5 × upper limits 
of normal (ULN) in the absence of a concomitant bilirubin increase (see point 3 below) 
3. One or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN in the presence of a total bilirubin increase >2 ×ULN or an 
international normalized ratio (INR) >1.5 without findings of cholestasis or other alternate 
etiology to explain the elevations (i.e., “Hy’s Law cases”) 
4. Two or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
6.3.2 Criteria for Premature Termination or Suspension of Investigational 
Sites 
A study site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant violation of Good Clinical Practice (GCP), protocol, or contractual agreement, 
is unable to ensure adequate study performance, or as otherwise permitted by the contractual 
agreement. 
6.3.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s) 
In the event that the sponsor, an IRB/independent ethics committee (IEC), or regulatory authority 
elects to terminate or suspend the study or the participation of an investigational site, a study-
specific procedure for early termination or suspension will be provided by the sponsor; applicable 
investigational sites will follow the procedure during the course of termination or study 
suspension. 


CVN766 
 
Study No. CVN766-101 
Page 26 of 79
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CONFIDENTIAL 
7.0 
SUBJECT POPULATION 
Screening for eligible subjects will be performed within 28 days prior to randomization or first 
dose.  
7.1 
Inclusion Criteria 
Subject eligibility is determined according to the following criteria prior to entry into the study: 
1. In the investigator's opinion, the subject can understand and sign the Informed Consent Form 
and comply with all protocol requirements.  
2. The subject is a healthy male or female adult who is 18 to 55 years of age, inclusive at the time 
of ICF. 
3. Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 32.0 kg/m2, inclusive 
at Screening.  
4. A male subject who is nonsterilized* and sexually active with a female partner of childbearing 
potential* agree to use two forms of adequate contraception* from signing the ICF throughout 
the study and for 90 days after the last dose. 
*Definitions and acceptable methods of contraception are defined in 
Section 9.1.13 Contraception and Pregnancy Avoidance Procedure, and 
reporting responsibilities are defined in Section 9.1.14 Pregnancy. 
5. A female subject of childbearing potential who complies with contraception requirements* or 
a female with no childbearing potential, defined as the subject has been surgically sterilized 
(hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (defined 
as continuous amenorrhea of at least 2 years and FSH>40 IU/L).  
      Note: hormoral contraceptives are not permitted as referenced in Table 3. 
7.2 
Exclusion Criteria 
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. Subject has received any investigational compound within 30 days prior to the first dose of 
study medication or within 5 half-lives, whichever is greater. 
2. Subject is a study site employee or an immediate family member of a study site employee.  
3. Subject has evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic 
disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious 
allergy, full-body allergic skin rash (including hives), psychiatric disorder, evidence of 
abnormal liver function test, evidence of abnormal renal function tests or other abnormality 
that may impact the ability of the subject to participate or potentially confound the study 
results.  
Note: Healthy volunteers with pre-existing stable disease, defined as diseases not requiring 
significant change in therapy or hospitalization for worsening disease during the 6 wks before 
enrolment, may be included at the discretion of the Investigator. 


CVN766 
Study No. CVN766-101 
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Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
4. There is any finding in the subject’s medical history, physical examination, or safety laboratory 
tests giving reasonable suspicion of a disease that would contraindicate taking CVN766 or a 
similar drug in the same class or that might interfere with the conduct of the study
5. Subject has a known hypersensitivity to any component of the formulation of CVN766.
6. Subject has a positive urine result for drugs of abuse at Screening or Inpatient Check-in (Day 
-1).
7. Subject has a history of a major psychiatric illness or currently receiving therapy for a 
psychiatric condition
8. Subject has a history of drug abuse or a history of alcohol abuse (more than 14 units/week) 
within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and 
drugs throughout the study.
9. Subject has taken any excluded medication, supplements, or food products listed in the 
Excluded Medications and Dietary Products table as listed in Table 3: Excluded Medications 
and Dietary Products.
10. Male subjects who do not agree to all the following rules: when sexually active with a female 
partner(s) of childbearing potential during the study, and for 90 days after the last dose of study 
drug: a) must use two acceptable methods of birth control (condom or surgical sterilization 
combined with highly effective method of contraception for the female partner) and b) refrain 
from sexual activity with female partners who do not use an acceptable method of birth control. 
Barrier contraception (condom) must be used by all-male subjects who were not surgically 
sterilized at least 90 days prior to screening. Male subjects must also agree to refrain from 
sperm donation during the study and until 90 days after the last dose of the study drug.
11. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova 
during the study or 30 days after the last dose of the study drug. Women of childbearing 
potential must agree to practice an acceptable method of birth control (e.g., , intrauterine 
device, barrier, abstinence).
Note: Hormonal contraceptives are not permitted as referenced in Table 3.
*Definitions and acceptable methods of contraception are defined in Section 9.1.13.
Contraception and Pregnancy Avoidance Procedure and reporting responsibilities are
defined in Section 9.1.14 Pregnancy. 
12. Subject has previously had a seizure or convulsion (lifetime, with the exception of febrile
seizures), including absence seizure.
13. Subject has current o recent (within 6 months) gastrointestinal disease that would be expected
to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention
known to impact absorption [e.g., bariatric surgery or bowel resection], esophageal reflux,
peptic ulcer disease, erosive esophagitis, or frequent [i.e., more than once per week] occurrence
of heartburn).
14. Subject has a history of cancer or other malignancy, except for basal cell carcinoma or
squamous cell carcinoma that has been in remission for at least 3 years prior to Day 1.


CVN766 
 
Study No. CVN766-101 
Page 28 of 79
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CONFIDENTIAL 
15. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody, or a human immunodeficiency virus infection at Screening. 
16. Subject who regularly use nicotine-containing products (including but not limited to cigarettes, 
electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). The 
casual users may participate but must agree to refrain from the time of Screening for the 
duration of the study or a positive urine cotinine test at Inpatient Check-in (Day 1). 
17. Subject has poor peripheral venous access (defined as more than three failed attempts to 
cannulate. 
18. Subject has donated or lost 450 mL or more of their blood volume (including plasmapheresis) 
or had a transfusion of any blood product within 45 days prior to Day 1. 
19. Subject has an abnormal (CS) ECG at Screening or Inpatient Check-in (Day -1). Entry of any 
subject with an abnormal (NCS) ECG must be approved and documented by signature by the 
Investigator or medically qualified sub-investigator.  
20. Subject has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 
40 to 90 mm Hg for diastolic, confirmed with repeat per PI discretion, at the Screening Visit 
or Inpatient Check-in (Day -1). 
21. Subject has a resting heart rate outside the range of 40 to 100 bpm, confirmed with repeat per 
PI discretion, at the Screening Visit or Inpatient Check-in (Day -1). 
22. Subject has a QT interval with Fridericia’s correction method (QTcF) >450 ms (males) or 
>470 ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat testing 
at the Screening Visit or Inpatient Check-in (Day -1) Visit. 
23. Subject has abnormal Screening or Inpatient Check-in (Day -1) laboratory values that suggest 
a CS underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 
the ULN, confirmed with one repeat testing. 
24. Subject has a risk of suicide according to the investigator’s clinical judgment or has made a 
suicide attempt in the previous 2 years. 
7.3 
Excluded Medications and Dietary Products 
Use of the agents in Table 3 (prescription or nonprescription) is prohibited from the time points 
specified until completion of all study activities. 


CVN766 
 
Study No. CVN766-101 
Page 29 of 79
Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
Table 3 
Prohibited Medications and Dietary Products 
28 days prior to Inpatient Check-in  
 
7 days prior to Inpatient Check-in  
72 hours prior to Inpatient 
Check-in  
 
Prescription medications (including 
hormonal contraceptives) 
OTC medications, including 
antacids, proton-pump inhibitors, 
and H2 receptor antagonists (a) 
Products containing caffeine or 
xanthine (e.g., tea or coffee) 
Nicotine-containing products 
Vitamin supplements 
poppy seeds 
Nutraceuticals (e.g., St. John’s wort, 
ginseng, kava kava, ginkgo biloba, 
Chinese herbs, and melatonin) 
Orexin receptor antagonists 
including suvorexant (Belsomra®), 
lemborexant (Dayvigo®), and 
related compounds 
 
Immunization/Vaccines (b) 
Alcohol-containing products 
 
Known strong inhibitors/inducers of 
CYPs 3A4/5 (c) 
 
 
CYP= cytochrome P-450, OTC=over the counter. 
(a) Occasional use of acetaminophen (~1 g/day) and 400mg ibuprofen TDS when required or other medication as 
approved by the sponsor’s Medical Monitor on a case-by-case basis is allowed except on Day 1 
(b) Inclusive of but not limited to H1N1 and flu vaccinations. Subjects who have received the COVID-19 Vaccine 
between -10 and -28 days may participate provided they did not experience any side effects of any description. 
COVID-19 vaccine doses may be administered 7 days post-study medication dosing.  
(c) e.g., chloramphenicol, clarithromycin, ketoconazole. 
Subjects must be instructed not to take any medications during study participation, including over-the-counter drug 
products, without first consulting with the investigator. 
7.4 
Diet, Fluid, Activity Control  
Subjects will be confined to the clinic for each of the dosing days as well as a period of time 
sufficient to collect additional post-dose PK samples and monitor for safety and tolerability (Day 
-1 through Day 4 for single-dose cohorts and Day-1 through Day 9 for multiple-dose cohorts). 
During confinement, subjects will be provided 3 standard meals and a snack per day, each 
containing approximately 30% fat (relative to the total calories). The meals served on the day of 
dosing should be similar in nutritional content for each subject in the study. The study menu should 
be recorded and submitted to the study file with a copy provided to the sponsor prior to the start 
of the study. Breakfast will not be provided on dosing days until at least 1 hour after dose 
administration unless otherwise indicated (i.e., Days 2-6 for MAD cohorts). The meal start and 
stop times and percentage of the meal consumed will be recorded in the source and appropriate 
electronic case report form (eCRF) for all meals served on dosing days.  
If a blood draw or any study procedure coincides with a meal, the blood draw will take precedence, 
followed by the study procedure and then the meal. 
Subjects will remain in bed at a semi-supine position for 4 hours following the dose administration, 
except as necessitated by the occurrence of an AE or study procedures (e.g., obtaining a 12-lead 
ECG). Subjects must refrain from strenuous exercise from 72 hours before Inpatient Check-in and 
until check-out. 


CVN766 
 
Study No. CVN766-101 
Page 30 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
On the dosing days where extensive PK and/or CSF sampling is indicated (i.e., single-dosing Day 
1 and first and last multiple-dose days, e.g., days 1 and 7), CVN766 or placebo suspension will be 
administered with approximately 240 mL of water after a fast of at least 10 hours. Subjects will 
continue to fast for an additional 4 hours after dosing and eat lunch following the 4-hour PK blood 
and CSF collection. Subjects may consume water ad libitum except for 1 hour before and 1 hour 
after drug administration. 
For the food effect cohort (S3), single-dose administration will be administered after ingesting a 
standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect 
bioavailability and fed bioequivalence studies, Dec 2002). Subjects will finish the entire content 
of their breakfast within 25 minutes and will receive an investigational product 30 minutes (±5 
minutes) after beginning the meal. The S3 (food effect) cohort meals may be staggered to ensure 
dosing occurs 30 minutes after the beginning of the meal. 
Subjects will also fast for at least 10 hours prior to safety laboratory collection times as indicated. 
However, consumption of water as desired is permitted during this time, except for dosing days, 
as indicated above. 
7.5 
Criteria for Discontinuation or Withdrawal of a Subject 
The primary reason for discontinuation or withdrawal of the subject from the study or study 
medication should be recorded in the eCRF using the following categories. For screen failure 
subjects, Section 9.1.15. 
1. The subject has experienced a PTE or AE that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health or the subject is unwilling to 
continue because of the PTE or AE. 
2. Liver Function Test (LFT) Abnormalities 
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests, until a subject’s laboratory profile has returned to 
normal/baseline status) if the following circumstances occur at any time during study 
medication treatment: 
– ALT or AST >8 × ULN, or 
– ALT or AST >5 × ULN and persists for more than 2 weeks, or 
– ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or INR >1.5, 
or 
– ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
3. Significant protocol deviation. The discovery post-randomization that the subject failed to 
meet protocol entry criteria or did not adhere to protocol requirements and continued 
participation poses an unacceptable risk to the subject’s health. 
4. Lost to follow-up. The subject did not return to the clinic and attempts to contact the subject 
were unsuccessful. Attempts to reach the subject must be documented. 


CVN766 
 
Study No. CVN766-101 
Page 31 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
5. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF. 
Note: All attempts should be made to determine the underlying reason for the withdrawal, and, 
where possible, the primary underlying reason should be recorded (i.e., withdrawal due to an 
AE). 
6. The sponsor, IRB, IEC, or regulatory agency terminates the study. 
7. Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
7.6 
Procedures for Discontinuation or Withdrawal of a Subject 
The investigator must discontinue a subject’s study participation at any time during the study when 
the subject meets the study discontinuation criteria described in Section 7.5. In addition, a subject 
may discontinue his or her participation without giving a reason at any time during the study. 
Should a subject’s involvement be terminated, the primary criterion for termination must be 
recorded by the Investigator. In addition, efforts should be made to perform all procedures 
scheduled for the Early Termination Visit. Discontinued or withdrawn subjects may be replaced 
at the  Sponsor’s discretion. 
Participants who withdraw from the study prior to dosing may be replaced. If a participant 
withdraws after the first dose of study medication or placebo, no replacement will occur. 


CVN766 
 
Study No. CVN766-101 
Page 32 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
8.0 
CLINICAL TRIAL MANAGEMENT 
8.1 
Study Medication and Materials 
This section contains information regarding all medication and materials provided directly by the 
sponsor and/or sourced by other means required by the study protocol, including important 
sections describing the management of clinical trial material. 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling 
Study drug refers to CVN766 and matching placebo. Study drug will be provided in bulk supply. 
An unblinded pharmacist will manage and prepare doses as oral suspensions as needed throughout 
the study.  
In this protocol, the term study medication refers to all or any of the drugs defined below. 
8.1.1.1 Investigational Drug 
CVN766 and Matching Placebo 
CVN766 drug substance is supplied as a bulk powder to the clinical site and then compounded 
into oral suspensions. A matching placebo suspension containing all of the components of the 
active oral suspension with the exception of the drug substance will also be compounded by the 
site. Compounding instructions will be outlined in a separate pharmacy manual and provided by 
the sponsor. See Table 4 for the composition of the drug product and matching placebo 
suspensions.  
The oral suspensions will be labeled with the appropriate study information and caution 
statements.  
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo 
Component 
CVN766 Oral Suspension (individual dose) 
Matchin
g Placebo 
CVN766 drug substance 
5 mg 
15 mg 
45 mg 
125 mg 
250 mg 
NA 
 Commercial 
suspending 
vehiclea 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
NA=Not applicable;  
a An off-the-shelf commercial suspending vehicle will be used, and the details of the vehicle will be provided in the 
Pharmacy Manual. 
8.1.1.2 Ancillary Materials  
Ancillary materials will be provided by either the clinical site and/or the sponsor based on 
availability.  
Ancillary material details are provided in the pharmacy manual. 
Unused ancillary materials, if provided by the sponsor, will be accounted for and disposed of as 
directed by the sponsor or their designee.  


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CVN766 
 
Study No. CVN766-101 
Page 34 of 79
Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
 
Table 5 
Planned Single and Multiple Dose Levels by Cohort 
Single-Dose Cohorts 
 
 
 
Cohort 
Planned Treatment* 
No. of Subjects 
Medication Type 
S1  
CVN766 5 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S2 
CVN766 15 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S3 Fasted 
CVN766 45 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S3 Fed (Same 8 subjects as 
in the S3 FASTED cohort) 
CVN766 45 mg 
6 
oral suspension 
 
Placebo 
2 
oral suspension 
S4 
CVN766 125 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S5 
CVN766 250 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
Multiple Dose Cohorts 
Cohort 
Planned Treatment* 
No. of Subjects 
Medication Type 
M1  
CVN766 45 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
M2  
CVN766 125 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
M3 
CVN766 250 mg 
6 
oral suspension 
 
Placebo 
2 
oral suspension 
* Dose (active or placebo) is in 10 mL of suspension. 
8.1.4 Overdose 
An overdose is defined as a known, deliberate, or accidental administration of an investigational 
drug, to or by a study subject, at a dose above that assigned to that individual subject according to 
the study protocol. 
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF, in order to capture this important safety information consistently in the database. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE eCRF(s) according to Section 9.7.2, PTEs and AEs. 
Serious adverse events (SAEs) associated with an overdose should be reported according to the 
procedure outlined in Section 9.7.4, Collection and Reporting of SAEs. 
In the event of an overdose, supportive measures should be employed as needed, e.g., 
administration of supportive therapy as dictated by the subject’s clinical status, removal of 
unabsorbed material from the gastrointestinal tract, or initiation of additional clinical monitoring.  


CVN766 
 
Study No. CVN766-101 
Page 35 of 79
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CONFIDENTIAL 
8.2 
Investigational Drug Assignment and Dispensing Procedures 
Subjects will be assigned to receive a unique randomization number.  
The clinical site will use the unique identifier to facilitate the pre-labeling of PK samples. It should 
also be contained on the PK transport vials shipped to the bioanalytical laboratory and will be used 
by the laboratory to report the subject data results. This unique identifier should only be used for 
the purposes described in this section. This identifier will be assigned upon randomization in the 
order in which subjects receive their first dose of the study drug.   
8.3 
Randomization Code Creation and Storage  
The sponsor or their designee will generate the randomization schedule and provide a copy to the 
site pharmacist and bioanalytical laboratory prior to the start of the study. All randomization 
information will be stored in a secured area, accessible only by authorized personnel.  
8.4 
Investigational Drug Blind Maintenance 
The investigational drug blind is maintained through a randomization schedule held by the 
dispensing pharmacist. 
8.5 
Unblinding Procedure 
The investigational drug blind shall not be broken by the investigative staff unless information 
concerning the investigational drug is necessary for the medical treatment of the subject. All study 
assessments and causality assessments should be performed, if possible, prior to unblinding. In the 
event of a medical emergency, if possible, the medical monitor should be contacted to discuss the 
need for unblinding before the investigational drug blind is broken. 
Unblinding envelopes will be supplied to the site prior to the first subject dosing and stored in a 
central and secure place to ensure access in the event of an emergency.  Study staff will be trained 
on unblinding procedures. 
The sponsor must be notified as soon as possible if the investigational drug blind is broken. The 
date, time, and reason the blind is broken must be recorded in the source documents, and the same 
information (except the time) must be recorded on the eCRF. 
If any site personnel inadvertently become unblinded, the sponsor must be notified, and the SRG 
will determine whether to discontinue dosing or withdraw from the study of all affected subjects. 
No change should be made to any assessment of the subject after unblinding. 
Following assessment of the AE data and pre-defined criteria for study termination, dose escalation 
may be interrupted/stopped and the blind broken for further analysis. Based on a review of 
unblinded data, the sponsor, in consultation with the Investigator, will decide if and how it is 
appropriate for the study to proceed. 
The Randomization schedule for all subjects will be released for analysis after the database for 
these cohorts is locked. The Investigator will be unblinded after database lock for all the cohorts 
if necessary. 


CVN766 
 
Study No. CVN766-101 
Page 36 of 79
Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
8.6 
Accountability and Destruction of Sponsor-Supplied Drugs 
Drug supplies will be counted and reconciled at the site before being returned to the sponsor or 
designee or being destroyed.  
The investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to subjects enrolled in the study. To document appropriate 
use of study medication, the investigator must maintain records of all study medication delivery to 
the site, site inventory used by each subject, and return to the sponsor or designee. 
Upon receipt of study medication, the investigator or designee must verify the contents of the 
shipments against the packing list, ensure the quantity is correct, and the medication is received 
within the labeled storage conditions. If quantity and conditions are acceptable, the investigator or 
designee should acknowledge the receipt of the shipment by signing the bottom half of the packing 
list and send via email and per instructions provided on the form. If any discrepancies exist 
between the packing list and the actual product received, the sponsor must be contacted to resolve 
the issue. The packing list should be filed in the investigator’s essential document file. The 
investigator must maintain 100% accountability for all study medication received and dispensed 
during their entire participation in the study. Proper drug accountability includes, but is not limited 
to: 
• Continuously monitoring expiration dates 
• Frequently verifying that actual inventory matches documented inventory 
• Verifying that the log is completed for the drug lot used to prepare each dose 
• Verifying that all containers used are documented accurately on the log 
• Verifying that required fields are completed accurately and legibly 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
The investigator or designee must record the current inventory of all study medication on a 
sponsor-approved drug accountability log. The following information will be recorded at a 
minimum: protocol number and title, name of the Investigator, site identifier and number, 
description of study medication, expiry date, and amount dispensed, including the initials of the 
person dispensing and receiving the study medication. The log should include all required 
information as a separate entry for each subject to whom study medication is dispensed. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform clinical study material accountability and reconciliation before clinical study 
materials are returned to the sponsor or its designee for destruction or destroyed at the site, as 
applicable. The investigator will retain the original documentation regarding clinical study 
material accountability, return, and/or destruction, and copies will be sent to the sponsor or 
designee. 
The investigator will be notified of any expiry date or retest date extension of clinical study 
material during the study conduct. On expiry date notification from the sponsor or designee, the 
site must complete all instructions outlined in the notification, including segregation of expired 
clinical study material for return to the sponsor or its designee for destruction. 


CVN766 
 
Study No. CVN766-101 
Page 37 of 79
Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
9.0 
STUDY PLAN 
9.1 
Study Procedures 
The following sections describe the study procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel whenever possible. The 
Schedule of Study Procedures is located in Appendix A. 
9.1.1 Informed Consent Procedure 
The requirements of the ICF are described in Section 14.2. 
The ICF must be obtained prior to the subject entering the study and before any protocol-related 
procedures are performed. 
A unique subject screening number (of the form xx-xxx), the first two numbers for the site, 
subsequent three numbers for subject identification will be assigned to each subject when the ICF 
is obtained. This subject ID will be used until the subject is assigned their 4-digit randomization 
number. 
9.1.1.1 Pharmacogenomic and Cerebrospinal Fluid Informed Consent Procedure 
Pharmacogenomics and cerebrospinal fluid informed consent is a component of the overall study 
ICF. The requirements are described in Section 14.2. 
The pharmacogenomic and (for applicable cohorts) cerebrospinal fluid sample collection is 
mandatory. 
9.1.2 Demographics, Medical History, and Medication History Procedure 
Demographic information to be obtained will include date of birth, sex, ethnicity, race as described 
by the subject, smoking status, and caffeine consumption at Screening. 
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases that stopped at or prior to signing the ICF. Ongoing conditions are 
considered concurrent medical conditions (see Section 9.1.7). 
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days before signing ICF. 
9.1.3 Physical Examination Procedure 
A physical examination performed by the investigator or medical officer consist of the following 
body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; 
(5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; 
(9) nervous system; (10) lymph nodes; (11) abbreviated neurological exam; and (12) other.  
Any abnormal change from the baseline physical examination (Screening and Inpatient Check-in 
[Day -1]) must be assessed as not CS or CS by the investigator and recorded in the source document 
and eCRF.  


CVN766 
 
Study No. CVN766-101 
Page 38 of 79
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CONFIDENTIAL 
All CS findings/changes, as determined by the investigator, from the baseline physical 
examination will be recorded as a PTE or concurrent medical condition in the source document 
and on the appropriate eCRF described in Section 9.8.1 or Section 9.8.2.  
On subsequent examinations, any abnormal change from the pretreatment physical examination 
assessment occurring immediately prior to the start of the investigational drug Inpatient Check-in 
(Day -1) must be assessed as not clinically significant (NCS) or CS by the investigator and 
recorded in the source document and eCRF. Any CS change or new diagnosis as a result of a CS 
change, as determined by the investigator, will be recorded as an AE in source documentation and 
on the PTE/AE eCRF. 
9.1.4 Weight, Height, and BMI 
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below:  
Height is recorded centimeters without decimal places, and for weight, it is kilograms (kg) with 1 
decimal place. BMI should be derived as: 
Metric:  
BMI = weight (kg)/[height (m)]2 
Results for BMI will be expressed with 1 decimal place. 
Example: 
Height=176 cm (or 1.76 m), weight=79.2 kg; BMI=79.2/1.762=25.57 kg/m2 captured as 
25.6 kg/m2.  
9.1.5 Vital Sign Procedure 
Vital signs will include tympanic body temperature, respiration, pulse, and blood pressure and be 
collected at timepoints specified in the Schedule of Study Procedures (Appendix A). For eligibility 
determination, the pulse will not be derived from ECG. Pulse and blood pressure will be measured 
after at least 5 minutes supine and again after 2 minutes standing.  
Vital signs should be measured at the same time (+/- 1 hour) of the day across visits if possible. 
When vital signs are scheduled at the same time as blood draws, the blood draw will take priority, 
and vital signs will be obtained within approximately 0.25 hours before or after the scheduled 
blood draw. 
9.1.6 Documentation of Concomitant Medications 
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by the sponsor. At each study visit, subjects will be asked whether they have taken 
any medication other than the study medication (used from signing of ICF through the end of the 
study), and all medication, including vitamin supplements, over-the-counter medications, and oral 
herbal preparations, must be recorded in the eCRF. Documentation will include generic medication 
name, dose, unit, frequency, route of administration, start and end dates, and reason for use. 


CVN766 
 
Study No. CVN766-101 
Page 39 of 79
Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
9.1.7 Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at the signing of ICF. This includes CS laboratory, ECG, or physical examination abnormalities 
noted at Screening examination. The condition (i.e., diagnosis) should be described. 
9.1.8 ECG Procedure  
Standard 12-lead ECGs will be recorded at timepoints specified in the Schedule of Study 
Procedures (Appendix A). Triplicate ECGs will be taken at each scheduled time. Additional 
unscheduled ECGs may be recorded where clinically necessary for subject safety. 
When an ECG is scheduled at the same time as blood draws or vital signs, then the blood draws 
and vital signs will take priority, and the ECG will be obtained within 0.5 hour before or after the 
scheduled blood draw/vital sign assessment. If an ECG coincides with a meal, ECG will take 
precedence, followed by the meal. 
All stationary 12-lead ECG machines will be supplied by the site. Subjects should be in a supine 
position following an approximate 10-minute rest period for ECG recordings. Should technical 
difficulties occur during the recording of the ECG, a reasonable attempt should be made to repeat 
the ECG shortly after the failed attempt.  
ECGs will be read automatically, and also, the investigator or sub-investigator will manually 
interpret the ECG using 1 of the following categories: within normal limits, abnormal but not CS, 
or abnormal and CS. Abnormal QTc readings will be manually recalculated and reported by the 
Investigator on the eCRF. All 12-lead ECGs will be stored for manual measurement of intervals, 
if necessary. Twelve-lead ECGs will be recorded using an ECG machine that automatically 
calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and 
QTcF and QTcB (Fridericia’s and Bazett’s correction) intervals. Paper ECG traces will be 
recorded for 10 seconds at a standard paper speed of 25 mm/sec, and gain of 10 m/mV or digital 
recordings will be used.  
One copy of the 12-lead ECG with the physician’s signature and date of assessment will be filed 
with the source documents and captured in the appropriate eCRF. If the original ECG is printed 
on thermal paper, the ECG report must be photocopied and certified. The photocopy will be filed 
with the original ECG in the source. 
All ECGs will be recorded at the time points detailed in Appendix A. 
9.1.9 Pharmacogenomic Sample Collection 
Every subject must sign ICF/be consented to the sampling of whole blood for pharmacogenomic 
analysis to participate in the study. 
One whole blood sample for DNA isolation and genotyping will be collected at time points 
specified in the Schedule of Study Procedures (Appendix A) into plastic dipotassium 
ethylenediamine-tetra acetic acid (K2EDTA) spray-coated tubes and stored under frozen 
conditions. In addition, two whole blood samples will be collected at time points specified in the 
Schedule of Study Procedures (Appendix A) for ribonucleic acid (RNA) pharmacogenomic 
analysis. The pre-dose RNA blood samples should be collected under fasted conditions and prior 
to any other blood collection. 


CVN766 
 
Study No. CVN766-101 
Page 40 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
DNA may be evaluated for the genetic contribution to how the drug is broken down or affects the 
body. This is called a “pharmacogenomics research study.” Specific purposes of this study include: 
• Identifying genetic reasons why certain people respond differently to CVN766 
• Finding out more information about how CVN766 works 
• Generating information needed for research, development, and regulatory approval of tests to 
predict response to CVN766 
• Identifying variations in genes related to the biological target of CVN766 
This information may be used, for example, to develop a better understanding of the safety and 
efficacy of CVN766 and other study medications and for improving the efficiency, design, and 
study methods of future research studies. 
The samples will be stored no longer than 15 years after completion of the CVN766 study and/or 
until the drug development of CVN766 is no longer actively pursued by the sponsor or its 
collaborators. No samples will be stored for longer than permitted by the applicable law, and 
samples will be destroyed upon notification from the sponsor. “Stored samples” in this context are 
defined as samples that are double coded (the samples are stripped of all personal identifying 
information but a key links the samples to the clinical data collected from the sample donor) and 
are used in the analysis of investigational drug or related drug. 
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; every 
subject must sign the ICF in order to participate in this study. DNA samples will be collected and 
may be used to evaluate drug metabolic enzyme and transporter polymorphisms that may 
contribute to the variability in the PK of CVN766. Also, since pharmacogenomics is an evolving 
science, many genes and their functions are not yet fully understood. Future data may suggest a 
role of some of these genes in drug response, which may lead to additional hypothesis-generating 
exploratory research and diagnostic development on stored samples. 
If necessary and feasible, a second aliquot of blood may be taken if isolation of DNA and RNA 
from the first sample was not successful or possible. 
Samples will be frozen at -70°C or lower and shipped separately on dry ice prior to extraction and 
storage at -70°C or lower. Samples should not be allowed to thaw until processed. 
Detailed instructions for the handling and shipping of samples are provided in a separate lab 
manual. 
Genotyping on collected samples may be deferred until after the completion of the study’s in-life 
activities. 
Each pharmacogenomic sample for a study subject should be identifiable on the requisition form 
with the 4-digit randomization number. 


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CVN766 
 
Study No. CVN766-101 
Page 43 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
9.1.11 PK Parameters 
PK parameters of CVN766 will be derived using non-compartmental analysis methods from the 
concentration-time data for all evaluable subjects. Actual sampling times, rather than scheduled 
sampling times, will be used in all computations involving sampling times. The following PK 
parameters will be determined from concentrations of CVN766 in plasma and CSF:  
 
Symbol/Term 
Definition 
Plasma 
AUCt 
Area under the plasma concentration-time curve from the time of dosing to the time of the 
last measurable concentration 
AUC∞  
Area under the plasma concentration-time curve from time 0 to infinity, calculated as 
AUC∞=AUCt+Clast/λz, where Clast is the last quantifiable concentration. 
AUC24 
Area under the plasma concentration-time curve from time 0 to 24 hours, calculated using 
the linear trapezoidal rule. 
AUCτ 
Area under the plasma concentration-time curve over the dosing interval (τ) 
Cmax 
Maximum observed plasma concentration. 
Cmin 
Minimum observed plasma concentration; pre dose trough concentration 
Minimum observed plasma concentration at steady state, on last day of dosing 
CL/F 
 
Apparent clearance after extravascular administration, calculated as Dose/AUC∞ after a 
single dose. 
CL/Fss 
Apparent clearance after extravascular administration at steady state, calculated as 
Dose/AUCtau 
λz 
Terminal elimination rate constant, calculated as the negative of the slope of the log-linear 
regression of the natural logarithm concentration-time curve during the terminal phase 
t1/2z 
Terminal elimination half-life, calculated as ln(2)/λz. 
tmax 
Time to reach Cmax. 
Vz/F 
 
Apparent volume of distribution during the terminal phase after extravascular 
administration, calculated as (CL/F)/λz. 
Vz/Fss 
Apparent volume of distribution during the terminal phase after extravascular 
administration at a steady-state, calculated as (CL/Fss)/λz 
CSF 
plasma: CSF ratio 
ratio of the drug concentration in plasma vs. CSF 
 
Additional PK parameters may be calculated as appropriate. 
9.1.12 Procedures for Clinical Laboratory Samples 
All samples will be collected in accordance with acceptable laboratory procedures on the 
days/times stipulated in the Schedule of Study Procedures (Appendix A). 
Table 1 lists the tests that will be obtained for each laboratory specimen. 
Table 10 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Urinalysis 
Special 
RBC 
ALT 
pH 
Prolactin 


CVN766 
 
Study No. CVN766-101 
Page 44 of 79
Clinical Protocol – FINAL2.0 
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CONFIDENTIAL 
WBC with differential  
     (% and absolute) 
Hemoglobin 
Hematocrit 
Platelets 
PT/INR 
Albumin 
Alkaline phosphatase 
Lipase (d) 
AST 
Total bilirubin 
Direct bilirubin 
Total protein 
Creatinine 
Blood urea nitrogen 
Creatine kinase 
GGT 
Potassium 
Sodium 
Glucose 
Chloride 
Bicarbonate 
Calcium 
Specific gravity 
Protein 
Glucose 
Blood  
Nitrite 
Microscopic Analysis 
(only if positive dipstick 
results):  
RBC/high power field 
WBC/high power field 
Epithelial cells, casts 
etc. 
TSH 
(and if abnormal) 
reflex FT4 
Diagnostic Screening: 
Serum 
Urine/ Blood 
Serum hCG (a) 
FSH (b)  
Hepatitis panel, including HBsAg and anti-HCV (e) 
Human Immunodeficiency Virus (HIV) antibody 
Drug screen including amphetamines (AMP), 
barbiturates (BAR), benzodiazepines (BZO), 
cannabinoids, cocaine (COC), opiates (OPI), 
alcohol, cotinine © methamphetamines, 
methadone (MET), 
methylenedioxymethamphetamine (MDMA), 
phencyclidine (PCP), tetrahydrocannabinol 
(THC) 
Urine Pregnancy Test (a) 
FT4= free T4, FSH= follicle-stimulating hormone, GGT=γ-glutamyl transferase, hCG= human chorionic 
gonadotropin, PT=prothrombin time, RBC=red blood cells, TSH= thyrotropin, WBC=white blood cells. 
(a) Serum hCG pregnancy test will be done at Screening,  
 Urine 
Pregnancy 
Test 
will 
be 
done 
at 
Check-in 
(Day 
-1).  
(b) FSH level will be obtained for female subjects at Screening if they are postmenopausal (i.e., last regular menstrual 
cycle >2 years) and not surgically sterile. The result must be >40 IU/L for the subject to be enrolled. 
(c) 
To 
be 
performed 
at 
Screening 
and 
Inpatient 
Check-in 
(Day 
-1). 
(d) To be performed at Day -1 and 24- and 48-hours post-dose. 
(e) Screening Visit only 
The local laboratory will perform all clinical laboratory tests. The results of laboratory tests will 
be returned to the investigator, who is responsible for reviewing and filing these results. All 
laboratory safety data will be transferred electronically to the sponsor or designee in the format 
requested by the sponsor. The investigator will maintain a copy of the laboratory accreditation and 
the reference ranges for the laboratory used.  
Laboratory reports must be signed and dated by the Investigator or sub-investigator, indicating that 
the report has been reviewed and any abnormalities have been assessed for clinical significance. 
Subjects will be referred to their primary care physician for follow-up of any clinically significant 
findings or where the investigator or medically trained sub-investigator deems appropriate. 
All CS laboratory abnormalities must be recorded as a PTE/AE in the subject’s source documents 
and on the appropriate eCRF. A CS laboratory abnormality that has been verified by retesting will 


CVN766 
 
Study No. CVN766-101 
Page 45 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
be followed until the abnormality returns to an acceptable level or a satisfactory explanation has 
been obtained. 
If subjects experience ALT or AST >3 ×ULN, follow-up laboratory tests at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR should be performed within a 
maximum of 7 days and preferably within 48 to 72 hours after the abnormality was found. 
(Please refer to Section 7.5 for discontinuation criteria and Section 9.8.3 for the appropriate 
guidance on Reporting of Abnormal LFT in relation to ALT or AST >3 ×ULN in conjunction with 
total bilirubin >2 ×ULN). 
If the ALT or AST remains elevated >3 ×ULN on these 2 consecutive occasions, the investigator 
must contact the Medical Monitor for consideration of additional testing, close monitoring, 
possible discontinuation of study medication, discussion of the relevant subject details and possible 
alternative etiologies. The abnormality should be recorded as an AE (please refer to Section 9.8.3 
Reporting of Abnormal LFT for reporting requirements). 
9.1.13 Contraception and Pregnancy Avoidance Procedure 
From the date of signing of ICF, throughout the duration of the study, and for 30 days after the last 
dose of study medication, females of childbearing potential* must use two acceptable methods of 
contraception and must agree not to donate eggs; Nonsterilized** male subjects who are sexually 
active with a female partner of childbearing potential* must use two acceptable method(s) of 
contraception throughout the duration of the study, and for 90 days after the last dose of study 
medication. In addition, males must be advised not to donate sperm for 90 days after the last dose 
of study medication. 
Females of childbearing potential are defined as any female who has experienced menarche and 
who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not 
postmenopausal.  
Menopause is defined as at least 2 years since last regular menses with an FSH>40 IU/L or at least 
5 years since last regular menses, confirmed before any study medication is implemented. Male 
subjects with potentially postmenopausal partners who are under the age of 55 years must use 
condoms unless their partner’s postmenopausal status has been confirmed by FSH level.  
**Sterilized males should be at least 90 days post-vasectomy and confirm that they have obtained 
documentation of the absence of sperm in the ejaculate. 
Acceptable and highly effective methods of contraception are: 
Note: hormonal contraceptives are not permitted as referenced in Table 3. 
• 
Nonhormonal intrauterine device (IUD) 
• 
Bilateral tubal occlusion 
• 
Vasectomised subject/partner with documented azoospermia 90 days after procedure, 
if that partner is the sole sexual partner 
• 
Same-sex intercourse, if used consistently for the duration of the study and post dosing 
as specified above  


CVN766 
 
Study No. CVN766-101 
Page 46 of 79
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Complete abstinence, defined as the complete avoidance of heterosexual intercourse - is an 
acceptable form of contraception if used consistently throughout the duration of study and for the 
durations after dosing specified for males and females above. It is not necessary to use any other 
method of contraception when complete abstinence is elected. Females of childbearing potential 
who choose complete abstinence must continue to have pregnancy tests as per protocol. The 
reliability of sexual abstinence needs to be evaluated by the Investigator in relation to the duration 
of the clinical trial and the preferred and usual lifestyle of the subject. 
Subjects will be provided with information on acceptable methods of contraception as part of the 
subject's informed consent process and will be asked to sign an ICF stating that they understand 
the requirements for avoidance of pregnancy, egg donation, and sperm donation during the study.  
9.1.14 Pregnancy 
Women who are pregnant or breastfeeding will not be included in this study.  
If any subject is found to be pregnant during the study, she should be withdrawn, and any sponsor-
supplied drug should be immediately discontinued. In addition, any pregnancies in the partner of 
a male subject during the study or for 90 days after the last dose should also be recorded following 
authorization from the subject’s partner.  
If the pregnancy occurs during administration of active study medication, e.g., after Visit 1 or 
within 30 days of the last dose of active study medication, the pregnancy should be reported 
immediately, using a pregnancy notification form, to the contact listed in Section 1.0. 
Should the pregnancy occur during or after administration of the blinded drug, the investigator 
must inform the subject of their right to receive treatment information. If the subject chooses to 
receive unblinded treatment information, the individual blind should be broken by the investigator. 
Subjects randomized to placebo need not be followed. 
If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time she became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable). 
All reported pregnancies will be followed up to the final outcome using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation 
after the birth of the child will also be conducted for 8 weeks. 
9.1.15 Documentation of Screen Failure 
Investigators must account for all subjects who sign ICF. If the subject is not eligible at this visit, 
the investigator should complete the eCRF screen failure form. 
The primary reason for screen failure is recorded in the eCRF using the following categories: 
• PTE/AE 
• Did not meet inclusion criteria or did meet exclusion criteria 
• Significant protocol deviation 
• Lost to follow-up 


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• Voluntary withdrawal 
• Study termination 
• Other 
Subject numbers assigned to subjects who fail screening should not be reused.  
If a subject fails screening, but is later successfully rescreened, the data for the subject will be 
entered as if these were two separate subjects. Therefore, the data should be entered as follows: 
1. The screen failure data should be entered as a screen failure subject. 
2. Rescreened subjects should be assigned a new subject number and treated as a stand-alone 
subject. 
9.1.16 Documentation of Randomization 
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for randomization into the treatment phase. 
If the subject is found to be not eligible for randomization, the investigator should record the 
primary reason for failure on the applicable eCRF. 
9.2 
Monitoring Subject Treatment Compliance 
Study medication will be administered while subjects are under observation in the clinical research 
unit. Following administration of the study medication, appropriate mouth and/or hand checks will 
be performed to ensure that the dose is swallowed and noted in the source document. The date and 
time of each dose will be recorded in the source documents and on the eCRFs. An inventory of the 
study medication supplies dispensed will be performed by the site pharmacist or authorized study 
designee and recorded onto the Drug Accountability Log in the subject’s source document records 
or equivalent. The exact dose time of consecutive subjects may be staggered to facilitate logistics 
at the site. 
9.3 
Schedule of Observations and Procedures 
The study-related procedures schedule for all evaluations is shown in Appendix A and is not 
duplicated in the following sections.  
9.3.1 Screening 
Subjects will be screened within 28 days prior to randomization. Subjects will be screened in 
accordance with predefined inclusion and exclusion criteria as described in Section 7.0. See 
Section 9.1.15 for procedures for documenting screening failures. Subjects who are screening 
failures may be screened a second time if their reason for failing screening is thought to be 
resolved. Rescreened subjects will receive a new Screening number. 
9.3.2 Inpatient Check-In 
All subjects will be admitted to the study clinic the day prior to randomization and first dose.  
Subjects participating in the food effect cohorts will also check into the study clinic the day prior 
to the scheduled dosing. 


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9.3.3 Final Visit (discharge day from clinic) 
Subjects will be confined to the study clinic for the duration of the treatment period to permit 
supervised dosing of study drug and repeat study assessments.  Subjects participating in the single-
dose study and food effect assessment will be discharged no sooner than 72 hours post-dose, and 
subjects participating in the multiple-dose study will be discharged no sooner than 48 hours 
following their last dose.   
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 
9.3.4 Early Termination 
Subjects who discontinue dosing or decide to check out of the study clinic early will be advised to 
allow the Investigator (or authorized designees) to complete early termination assessments for 
safety purposes prior to discharge. The reason for discontinuation must be documented in the 
source document and eCRF.  
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 
9.3.5 Follow-up Visit  
The Follow-up Visit will occur by telephone approximately 14 days (±2) after the final dose of 
study drug for the SAD cohorts and MAD cohorts unless abnormal CS findings were observed 
upon discharge or the SRG has determined additional PK sampling timepoints are indicated. In 
these cases, subjects must then be brought back to the clinic for re-evaluation per the investigator’s 
discretion.  
9.4 
Biological Sample Retention and Destruction  
In all cohorts except S3 (fed), blood serum will be obtained on Day -1 and Day 2, and the collected 
serum will be stored at -70C to enable additional, retrospective analyses as needed. Samples will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. 
Blood specimens for genome/gene analysis will be collected as described in Section 9.1.12, 
Pharmacogenomic Sample Collection. After extraction and purification, the genetic material will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. Blood and urine samples for PK analysis will be 
collected as described in Section 9.1.12, PK Sample Collection.  Once PK analysis is complete, 
backup plasma and urine samples will be preserved and retained at a biorepository selected by the 
sponsor for up to, but not longer than, 15 years or as required by applicable law, to enable the 
conduct of exploratory, qualitative, metabolite identification studies or measurement of target 
related biomarkers, should the sponsor decide these are informative. The sponsor has put a system 
to protect the subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction. 
The sample will be labeled with a unique sample identifier similar to labeling in the main study 
but using a code different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 


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code numbers; the samples are stripped of all personally identifying information, but a key linking 
the samples to clinical analysis data exists. This link means that the subject may be identified but 
only indirectly. The code numbers will be kept secure by or on behalf of the Sponsor. 
Subjects who consented and provided a pharmacogenomic sample for DNA and RNA analysis can 
withdraw their consent and request disposal of a stored sample at any time prior to analysis. The 
Investigator will notify the sponsor of any subject who has withdrawn consent for the DNA and 
RNA analysis. 
9.5 
Blood Volume 
Direct venipuncture or intravenous cannula is the preferred method of blood collection. Any other 
method will need to be approved by the sponsor. The maximum volume of blood at any single day 
is approximately 111 mL, with the maximum amount not to exceed 500mL for the duration of 
study participation.  
9.6 
CSF Volume 
CSF will be collected by lumbar puncture, performed by a skilled and qualified individual. The 
maximum volume of CSF to be collected will be approximately 10 mL per subject.  
9.7 
Definitions 
9.7.1 PTE 
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed the ICF to participate in a study but prior to administration of any study medication; it does 
not necessarily have to have a causal relationship with study participation. 
9.7.2 AE 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (e.g., a CS abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a drug whether or not it is 
considered related to the drug. 
9.7.3 Additional Points to Consider for PTEs and AEs 
An untoward finding generally may: 
• Indicate a new diagnosis or unexpected worsening of a pre-existing condition. (Intermittent 
events for pre-existing conditions underlying disease should not be considered PTEs or AEs) 
• Necessitate therapeutic intervention 
• Require an invasive diagnostic procedure 
• Require discontinuation or a change in dose of study medication or a concomitant medication 
• Be considered unfavorable by the investigator for any reason 


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• PTEs/AEs caused by a study procedure (e.g., a bruise after blood draw) should be recorded as 
a PTE/AE 
Diagnoses vs. signs and symptoms: 
• Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as a PTE(s) or as an AE(s). 
Laboratory values and ECG findings: 
• Changes in laboratory values or ECG parameters are only considered to be PTEs or AEs if 
they are judged to be CS (i.e., if some action or intervention is required or if the investigator 
judges the change to be beyond the range of normal physiologic fluctuation). A laboratory re-
test and/or continued monitoring of an abnormal value are not considered an intervention. In 
addition, repeated or additional noninvasive testing for verification, evaluation, or monitoring 
of an abnormality is not considered an intervention 
• If abnormal laboratory values or ECG findings are the results of pathology for which there is 
an overall diagnosis (e.g., increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as a PTE or as an AE 
Pre-existing conditions: 
• Pre-existing conditions (present at the time of signing of the ICF) are considered concurrent 
medical conditions and should NOT be recorded as PTEs or AEs. Baseline evaluations (e.g., 
laboratory tests, ECG, X-rays, etc.) should NOT be recorded as PTEs unless related to study 
procedures.  
• If a subject has a pre-existing episodic condition (e.g., asthma, epilepsy), any occurrence of an 
episode should only be captured as a PTE/AE if the episodes become more frequent, serious, 
or severe in nature; that is, investigators should ensure that the AE term recorded captures the 
change in the condition from Baseline (e.g., “worsening of…”) 
• If a subject has a concurrent degenerative condition (e.g., cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater extent 
than that which would be expected. Again, investigators should ensure that the AE term 
recorded captures the change in the condition (e.g., “worsening of…”) 
Worsening of PTEs or AEs: 
• If the subject experiences a worsening or complication of a PTE after starting administration 
of the study medication, the worsening or complication should be recorded appropriately as an 
AE.  
• If the subject experiences a worsening or complication of an AE after any change in study 
medication, the worsening or complication should be recorded as a new AE. Changes in 
severity of AEs /Serious PTEs: 
• If the subject experiences changes in the severity of an AE/serious PTE, the event should be 
captured once with the maximum severity recorded 


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Preplanned surgeries or procedures: 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to signing informed 
consent are not considered PTEs or AEs. However, if a preplanned procedure is performed 
early (e.g., as an emergency) due to a worsening of the pre-existing condition, the worsening 
of the condition should be captured appropriately as a PTE or an AE. Complications resulting 
from any planned surgery should be reported as AEs. 
Elective surgeries or procedures: 
• Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as PTEs or AEs,but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs 
Overdose: 
• Cases of overdose with any medication without manifested side effects are NOT considered 
PTEs or AEs, but instead will be documented on an Overdose page of the eCRF. Any 
manifested side effects will be considered PTEs or AEs and will be recorded on the AE page 
of the eCRF 
9.7.4 SAEs 
An SAE is defined as any untoward medical occurrence that at any dose: 
1. Results in DEATH. 
2. Is LIFE-THREATENING 
• The term “life-threatening” refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization 
4. Results in persistent or significant DISABILITY/INCAPACITY 
5. Leads to a CONGENITAL ANOMALY/BIRTH DEFECT 
6. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following: 
• May require intervention to prevent items 1 through 5 above 
• May expose the subject to danger, even though the event is not immediately life-
threatening or fatal or does not result in hospitalization 
• Includes any event or synonym described in the Medically Significant AE List (Table 11)  
PTEs that fulfill 1 or more of the serious criteria above are also to be considered SAEs and 
should be reported and followed up in the same manner (see Sections 9.8.1 and 9.8.2). 
 


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Table 11 
Medically Significant AE List (categorized as Serious Adverse Events) 
Term 
Acute respiratory failure/acute respiratory distress 
syndrome 
Hepatic necrosis 
Torsade de pointes / ventricular fibrillation / 
ventricular tachycardia 
Acute liver failure 
Anaphylactic shock 
Malignant hypertension 
Acute renal failure 
Convulsive seizure 
Pulmonary hypertension 
Agranulocytosis 
Pulmonary fibrosis 
Aplastic anemia 
Confirmed or suspected endotoxin shock 
Toxic epidermal necrolysis/Stevens-Johnson 
syndrome 
Confirmed or suspected transmission of infectious agent 
by a medicinal product 
 
Neuroleptic malignant syndrome / malignant 
hyperthermia 
 
Spontaneous abortion/stillbirth and fetal death 
 
9.7.5 Severity of PTEs and AEs 
The different categories of intensity (severity) are characterized as follows: 
Mild: 
The event is transient and easily tolerated by the subject. 
Moderate: 
The event causes the subject discomfort and interrupts the subject’s usual activities. 
Severe: 
The event causes considerable interference with the subject’s usual activities. 
9.7.6 Causality of AEs 
The relationship of each AE to study medication(s) will be assessed using the following categories: 
Related: 
An AE that follows a reasonable temporal sequence from the administration of a drug 
(including the course after withdrawal of the drug), or for which possible involvement of the 
drug can be argued, although factors other than the drug, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments, may also be responsible. 
Not Related: 
An AE that does not follow a reasonable temporal sequence from the administration of a drug 
and/or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments. 
9.7.7 Relationship to Study Procedures 
Relationship (causality) to study procedures should be determined for all PTEs and AEs. 
The relationship should be assessed as Related if the investigator considers that there is a 
reasonable possibility that an event is due to a study procedure. Otherwise, the relationship should 
be assessed as Not Related. 
9.7.8 Start Date  
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician. 


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9.7.9 Stop Date  
The stop date of the AE/serious PTE is the date at which the subject recovered, the event resolved 
but with sequelae, or the subject died. 
9.7.10 Frequency  
Episodic AEs/serious PTE (e.g., vomiting) or those which repeatedly occur over a period of 
consecutive days are intermittent. All other events are continuous. 
9.7.11 Action Concerning Study Medication  
• Drug withdrawn – a study medication is stopped due to the particular AE 
• Dose not changed – the particular AE did not require stopping a study medication 
• Unknown – only to be used if it has not been possible to determine what action has been taken 
• Not Applicable – a study medication was stopped for a reason other than the particular AE, 
e.g., the study has been terminated, the subject died, dosing with study medication was already 
stopped before the onset of the AE 
9.7.12 Outcome 
• Recovered/Resolved – Subject returned to first assessment status with respect to the 
AE/serious PTE 
• Recovering/Resolving – the intensity is lowered by one or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved, but has not 
returned to the normal range or to baseline; the subject died from a cause other than the 
particular AE/serious PTE with the condition remaining “recovering/resolving” 
• Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the 
intensity of the diagnosis, signs/ symptoms, or laboratory value on the last day of the observed 
study period had got worse than when it started; is an irreversible congenital anomaly; the 
subject died from another cause with the particular AE/serious PTE state remaining “Not 
recovered/not resolved” 
• Resolved with sequelae – the subject recovered from an acute AE/serious PTE but was left 
with permanent/significant impairment (e.g., recovered from a cardiovascular accident but 
with some persisting paresis 
• Fatal – the AEs/PTEs which are considered as the cause of death 
• Unknown – the course of the AE/serious PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study 


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9.8 
Procedures 
9.8.1 Collection and Reporting of AEs 
9.8.1.1 PTE and AE Collection Period 
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication Day 1 
or until screen failure. For subjects who discontinue prior to study medication administration, PTEs 
will be collected for the duration of study participation. 
Collection of AEs will commence from the time that the subject is first administered study 
medication Day 1. Routine collection of AEs will continue until 14 days following last dose. 
9.8.1.2 PTE and AE Reporting 
At each study visit, the investigator or designee will assess whether any subjective AEs have 
occurred. A neutral question, such as “How have you been feeling since your last visit?” may be 
asked. Subjects may report AEs occurring at any other time during the study. Subjects 
experiencing a serious PTE must be monitored until the symptoms subside and any clinically 
relevant changes in laboratory values have returned to baseline or there is a satisfactory explanation 
for the change. Non-serious PTEs, related or unrelated to the study procedure, need not be followed 
up for the purposes of the protocol. 
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or until there is a satisfactory explanation for the 
changes observed. All PTEs and AEs will be documented in the PTE/AE page of the eCRF, 
whether or not the investigator concludes that the event is related to the drug treatment. The 
following information will be documented for each event: 
1. Event term. 
2. Start and stop date and time. 
3. Frequency. 
4. Severity. 
5. Investigator’s opinion of the causal relationship between the event and administration of study 
medication(s) (related or not related) (not completed for PTEs). 
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details of 
the suspected procedure. 
7. Action concerning study medication (not applicable for PTEs). 
8. Outcome of event. 
9. Seriousness. 


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9.8.2 Collection and Reporting of SAEs 
When an SAE occurs through the AE collection period it should be reported according to the 
following procedure: 
An SAE form must be completed in English and signed by the investigator immediately or within 
24 hours of the first onset or notification of the event. The information should be completed as 
fully as possible but contain, at a minimum: 
• A short description of the event and the reason why the event is categorized as serious 
• Subject identification number 
• Investigator’s name 
• Name of the study medication(s) 
• Causality assessment 
The SAE form should be transmitted within 24 hours to the attention of the contact listed in Section 
1.0.  
Any SAE spontaneously reported to the investigator following the AE collection period should be 
reported to the sponsor if considered related to study participation. 
Reporting of Serious PTEs will follow the procedure described for SAEs. 
9.8.3 Reporting of Abnormal LFT 
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an LFT Increases eCRF must be completed 
providing additional information on relevant recent history, risk factors, clinical signs and 
symptoms, and results of any additional diagnostic tests performed. 
If a subject is noted to have ALT or AST >3 ×ULN and total bilirubin >2 ×ULN for which an 
alternative etiology has not been identified, the event should be recorded as an SAE and reported 
as per Section 9.8.2. The investigator must contact the Medical Monitor for discussion of the 
relevant subject details and possible alternative etiologies, such as acute viral hepatitis A or B or 
other acute liver disease or medical history/concurrent medical conditions. Follow-up laboratory 
tests as described in Section 9.1.8 must also be performed. In addition, an LFT Increases eCRF 
must be completed and transmitted with the SAE form (as per Section 9.8.3). 
9.9 
Follow-up of SAEs 
If information is not available at the time of the first report becomes available at a later date, the 
investigator should complete a follow-up SAE form or provide other written documentation and 
fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital notes 
(e.g., ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee, if requested. 
All SAEs should be followed up until resuspension or permanent outcome of the event. The 
timelines and procedures for follow-up reports are the same as those for the initial report. 


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9.9.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory 
Authorities  
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities and IRBs or IECs, as 
applicable, in accordance with national regulations in the countries where the study is conducted. 
Relative to the first awareness of the event by/or further provision to the sponsor or sponsor’s 
designee, SUSARs will be submitted to the regulatory authorities as an expedited report within 7 
days for fatal and life-threatening events and 15 days for other serious events, unless otherwise 
required by national regulations. The sponsor will also prepare an expedited report for other safety 
issues that might materially alter the current benefit-risk assessment of an investigational 
medicinal product or that would be sufficient to consider changes in the investigational medicinal 
products administration or in the overall conduct of the trial. The investigational site also will 
forward a copy of all expedited reports to his or her IRB or IEC in accordance with national 
regulations. 


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10.0 
STUDY-SPECIFIC COMMITTEES 
The Safety Review Group (SRG) will be comprised of the Investigator, Medical Monitor, 
Cerevance Medical Officer and may include other sponsor representatives. A pharmacokineticist 
and other subject matter experts may participate as needed. Responsibilities of the SRG are 
outlined in Section 6.1.3. 


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11.0 
DATA HANDLING AND RECORDKEEPING 
AEs, PTEs, medical history, and concurrent conditions will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization 
(WHO) Drug Dictionary. All terms will be coded using the dictionary version available at the start 
of the study. 
11.1 
CRFs (Electronic) 
Completed eCRFs are required for each subject who signs an informed consent. 
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRF. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. Data are transcribed directly onto eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by sponsor 
personnel (or designees) and will be answered by the site.  
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for change. Reasons for significant corrections should additionally be included.  
The Investigator must review the eCRFs for completeness and accuracy and must sign and date 
the appropriate eCRFs as indicated. Furthermore, the investigator must retain full responsibility 
for the accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The sponsor or its designee will be permitted to review the subject’s medical 
and hospital records pertinent to the study to ensure the accuracy of the eCRFs. The completed 
eCRFs are the sole property of the sponsor and should not be made available in any form to third 
parties, except for authorized representatives of appropriate governmental health or regulatory 
authorities, without the written permission of the sponsor. 
11.2 
Record Retention 
The investigator agrees to keep the records stipulated in Section 11.2 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated ICFs, subject authorization forms regarding the use of 
personal health information (if separate from the ICFs), an electronic copy of eCRFs, including 
the audit trail, and detailed records of drug disposition to enable evaluations or audits from 
regulatory authorities, the sponsor or its designees. Any source documentation printed on 
degradable thermal sensitive paper should be photocopied by the site and filed with the original in 
the subject’s chart to ensure long-term legibility. Furthermore, ICH E6 Section 4.9.5 requires the 
investigator to retain essential documents specified in ICH E6 (Section 8) until at least 2 years 
after the last approval of a marketing application for a specified drug indication being investigated 
or, if an application is not approved, until at least 2 years after the investigation is discontinued 
and regulatory authorities are notified. In addition, ICH E6 Section 4.9.5 states that the study 


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records should be retained until an amount of time specified by applicable regulatory requirements 
or for a time specified in the Clinical Study Site Agreement between the investigator and sponsor. 
Refer to the Phase 1 Site Specifications document for the sponsor’s requirements on record 
retention. The investigator should contact and receive written approval from the sponsor before 
disposing of any such documents. 


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12.0 
STATISTICAL METHODS 
12.1 
Statistical and Analytical Plans 
A statistical analysis plan (SAP) will be prepared and finalized prior to unblinding of the subject’s 
treatment assignment. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all study objectives. 
A targeted data review will be conducted prior to unblinding of the subject’s treatment assignment. 
This review will assess the accuracy and completeness of the study database, subject evaluability, 
and appropriateness of the planned statistical methods. 
12.1.1 Analysis Sets 
Safety Set 
The Safety Analysis Set will consist of all subjects who are enrolled and receive study drug. 
Subjects in this analysis set will be used for demographic, baseline characteristics, and safety 
summaries. 
PK Set 
The PK set will consist of all subjects who receive study drug and have at least 1 measurable 
plasma concentration. 
If any subjects are found to be non-compliant in dosing schedule or with incomplete data, a 
decision will be made on a case-by-case basis as to their inclusion in the analysis but will be 
presented in the subject listings. 
12.1.2 Analysis of Demographics and Other Baseline Characteristics 
Descriptive statistics (N, mean, SD, median, minimum, and maximum) will be generated for 
continuous demographic variables and baseline characteristics variables (age, height, weight, and 
BMI) for pooled placebo, CVN766 dose level, CVN766 overall, and overall. The number and 
percentage of subjects in each class of the categorical demographic variables and baseline 
characteristics variables (gender, ethnicity, and race) will be tabulated for pooled placebo, each 
CVN766 dose level, CVN766 overall, and overall. Individual subject demographic and baseline 
characteristics data will be listed. 
Demographic variables of screen failure subjects and reasons for screen failures will be 
summarized overall for subjects who are screened but not enrolled in the study. Individual 
demographic characteristics, date of informed consent, and reason for screen failure will be listed. 
12.1.3 PK Analysis 
The concentration of CVN766 in plasma, and CSF will be summarized by dose over each scheduled sampling time 
using descriptive statistics. Individual concentration data versus time will be presented in a data listing. Individual and 
mean plasma and CSF concentration data will be presented graphically.  Descriptive statistics (arithmetic mean, SD, 
median, minimum and maximum) will be used to summarize the plasma and CSF PK parameters for CVN766. In 
addition, geometric mean and coefficient of variation will be computed 
The effect of fed/fasting state on PK and bioavailability of CVN766 will be characterized. 


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CONFIDENTIAL 
Plots of Cmax and AUCs, as well as dose-normalized Cmax and AUCs, versus doses, will be 
generated. 
Dose proportionality will be tested for CVN766 Cmax and AUCs using a power model.  
A more detailed analysis will be presented in the SAP. 
12.1.4 Safety Analysis 
12.1.4.1 AEs 
All AEs will be coded by system organ class (SOC) and preferred term (PT) using MedDRA. 
Treatment-emergent AEs with onset occurring within 30 days (onset date – last date of dose +1 
≤30) after study drug administration will be listed and included in the summary tables. Treatment-
emergent AEs will be summarized by pooled placebo, each CVN766 dose level and CVN766 
overall by SOC and PT. The following summary tables will be included in the report: summary of 
TEAEs and drug-related AEs, relationship of AEs to study drug (related vs. not-related), severity 
of AEs, and related AEs. AEs leading to study drug discontinuation and SAEs will be listed. Data 
listings will be provided for all AEs, including PTE, TEAEs, AEs leading to study drug 
discontinuation, and SAEs. All AEs will be listed. 
12.1.4.2 Clinical Laboratory Evaluation 
Individual results of laboratory tests from hematology, chemistry, and urinalysis that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and change from baseline to post-dose 
laboratory data will be summarized for pooled placebo, each CVN766 dose level, and CVN766 
overall. All clinical laboratory data will be listed. 
12.1.4.3 Vital Signs 
Individual results of vital signs that are abnormal and CS will be summarized and listed. Baseline, 
post-dose, and changes from Baseline in vital sign measurements will be summarized by pooled 
placebo, each CVN766 dose level, and CVN766 overall. All vital sign data will be provided in the 
data listings. 
12.1.4.4 ECGs 
Individual results of quantitative ECG parameters from the 12-lead safety ECGs that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and changes from baseline in 
quantitative ECG parameters will be summarized by pooled placebo, each CVN766 dose level, 
and CVN766 overall. Shift tables may be generated for the investigator’s ECG interpretations that 
changed from baseline to the post-dose collections by the above groups. All ECG data will be 
provided in the data listings. 
12.1.4.5 Other Variables 
Physical exam findings and suicidal assessments will be presented in data listings. 
12.2 
Interim Analysis and Criteria for Early Termination 
No interim analysis is planned. 


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12.3 
Determination of Sample Size 
The sample size chosen of 8 subjects per cohort (6 active: 2 placebo) is considered to be sufficient 
for the evaluation of the safety, tolerability, and PK of each cohort. The sample size was not based 
on statistical power considerations.  


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13.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Study-Site Monitoring Visits 
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution guarantee access to source documents by the sponsor or its 
designee (contract research organization) and by the IRB or IEC. 
All aspects of the study and its documentation will be subject to review by the sponsor or designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, 
study medication, subject medical records, informed consent documentation, documentation of 
subject authorization to use personal health information (if separate from the ICFs), and review of 
eCRFs and associated source documents. It is important that the investigator and other study 
personnel are available during the monitoring visits and that sufficient time is devoted to the 
process. 
13.2 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
designee (and IRB or IEC, as required) to determine the appropriate course of action. There will 
be no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria. 
The site should document all protocol deviations in the subject’s source documents. In the event 
of a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessment. A Protocol Deviation Form should be completed by the site and signed by the sponsor 
or designee for any significant deviation from the protocol. 
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. Table 12 
defines the windows allowed for sample collections.  
Protocol Deviation Forms are to be completed for PK samples collected outside of the following 
intervals: 
Table 12 
Windows for PK Blood Sample Collection 
Minutes 
Nominal Sampling Time 
no more than 15 minutes pre-dose 
0 hour 
±5 
immediately post-dose to ≤6 hours 
±10 
>6 hours to ≤12 hours post-dose 
±15 
>12 hours to ≤24 hours 
±30 
>24 hours 
 


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13.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing 
visit. The auditor may ask to visit the facilities where laboratory samples are collected, where the 
medication is stored and prepared, and any other facility used during the study. In addition, there 
is the possibility that this study may be inspected by regulatory agencies, including those of 
Australia (i.e., Therapeutic Goods Administration [TGA]) and foreign governments (e.g., the 
FDA, the United Kingdom Medicines and Healthcare products Regulatory Agency, the 
Pharmaceuticals and Medical Devices Agency of Japan). If the study site is contacted for an 
inspection by a regulatory body, the sponsor should be notified immediately. The investigator and 
institution guarantee access for quality assurance auditors to all study documents as described in 
Section 13.1. 


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14.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual subjects (i.e., subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, 
and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct the study 
according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the “Responsibilities of the Investigator” that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities. 
14.1 
IRB and/or IEC Approval 
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. Those Americas sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services. 
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the ICFs, and, if applicable, subject recruitment materials and/or advertisements and other 
documents required by all applicable laws and regulations must be submitted to a central or local 
IRB or IEC for approval. The IRB’s or IEC’s written approval of the protocol and subject informed 
consent must be obtained and submitted to the sponsor or designee before the commencement of 
the study (i.e., before shipment of the sponsor-supplied drug or study-specific screening activity). 
The IRB or IEC approval must refer to the study by exact protocol title, number, and version date; 
identify versions of other documents (e.g., ICF) reviewed; and state the approval date. The sponsor 
will ship drug/notify site once the sponsor has confirmed the adequacy of site regulatory 
documentation and, when applicable, the sponsor has received permission from a competent 
authority to begin the trial. Until the site receives drug/notification, no protocol activities, 
including screening may occur. 
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by subjects, local safety reporting requirements, reports, and 
updates regarding the ongoing review of the study at intervals specified by the respective IRB or 
IEC, and submission of the investigator’s final status report to IRB or IEC. All IRB and IEC 
approvals and relevant documentation for these items must be provided to the sponsor or its 
designee. 
Subject incentives should not exert undue influence on participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor. 


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14.2 
Subject Information, Informed Consent, and Subject Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
applicable laws and regulations. The ICF, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and disclosures 
of the subject’s personal and personal health information for purposes of conducting the study. 
The ICF and the subject information sheet (if applicable) further explain the nature of the study, 
its objectives, and potential risks and benefits, as well as the date informed consent is given. The 
ICF will detail the requirements of the subject and the fact that he or she is free to withdraw at any 
time without providing a reason and without prejudice to their other medical care. 
The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and if applicable, the subject authorization form. The ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) must be approved by both the IRB or IEC 
and the sponsor prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject. It is the 
responsibility of the investigator to explain the detailed elements of the ICF, subject authorization 
form (if applicable), and subject information sheet (if applicable) to the subject. Information should 
be given in both oral and written form whenever possible and in the manner deemed appropriate 
by the IRB or IEC. In the event the subject is not capable of rendering adequate written informed 
consent, then the subject’s legally acceptable representative may provide such consent for the 
subject in accordance with applicable laws and regulations. 
The subject, or the subject’s legally acceptable representative, must be given ample opportunity 
to: (1) inquire about details of the study and (2) decide whether or not to participate in the study. 
If the subject, or the subject’s legally acceptable representative, determines he or she will 
participate in the study, then the ICF and subject authorization form (if applicable) must be signed 
and dated by the subject, or the subject’s legally acceptable representative, at the time of consent 
and prior to the subject entering into the study. The subject or the subject’s legally acceptable 
representative should be instructed to sign using their legal names, not nicknames, using blue or 
black ballpoint ink. The investigator must also sign and date the ICF and subject authorization (if 
applicable) at the time of consent and prior to the subject entering into the study; however, the 
sponsor may allow a designee of the investigator to sign to the extent permitted by applicable law. 
Once signed, the original ICF, subject authorization form (if applicable), and subject information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document 
the date the subject signs the informed consent in the subject’s medical record. Copies of the signed 
ICF, the signed subject authorization form (if applicable), and the subject information sheet (if 
applicable) shall be given to the subject. 
All revised ICFs must be reviewed and signed by relevant subjects or the relevant subject’s legally 
acceptable representative in the same manner as the original informed consent. The date the revised 
consent was obtained should be recorded in the subject’s medical record, and the subject should 
receive a copy of the revised ICF. 


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CONFIDENTIAL 
Subjects who consented and provided a pharmacogenomic sample for DNA analysis can withdraw 
their consent and request disposal of a stored sample at any time prior to analysis. Notify sponsor 
of consent withdrawal. 
14.3 
Subject Confidentiality 
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the sponsor’s clinical study database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or 
date of birth, and subject initials may be used to verify the subject and the accuracy of the subject’s 
unique identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (e.g., FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s study participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process (see Section 14.2). 
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (i.e., subject name, address, and other identifier fields 
not collected on the subject’s eCRF). 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy 
14.4.1 Publication and Disclosure 
The investigator is obliged to provide the sponsor with complete test results and all data derived 
by the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and/or advertisements, is the sole responsibility of the sponsor. 
The sponsor may publish any data and information from the study, including data and information 
generated by the investigator, without the consent of the investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and review 
of the document. All publications and presentations must be prepared in accordance with this 
section and the Clinical Study Site Agreement. In the event of any discrepancy between the 
protocol and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail. 
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. 


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14.4.2 Clinical Trial Registration  
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations, and guidance, the sponsor will register this clinical trial 
on ClinicalTrials.gov (and possibly on other publicly accessible websites) before the start of study.  
Sponsor contact information, along with the investigator’s city, state, country, and recruiting 
status, will be registered and available for public viewing. Once subjects receive investigator 
contact information, they may call the site and request enrollment into the trial. The investigative 
site(s) are encouraged to handle such trial inquiries according to their established subject screening 
process. If the caller asks additional questions beyond the topic of trial enrollment, they should be 
referred to the sponsor.  
14.4.3 Clinical Trial Results Disclosure  
If required at the conclusion of the study, the sponsor will post the results on ClinicalTrials.gov or 
other publicly accessible websites, as required by applicable national and local laws and/or 
regulations. 
14.5 
Insurance and Compensation for Injury 
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject compensation 
and treatment for injury. If the investigator has questions regarding this policy, he or she should 
contact the sponsor or sponsor’s designee. 


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CONFIDENTIAL 
15.0 
REFERENCES 
FDA Guidance for Industry: Food-effect bioavailability and fed bioequivalence studies (Dec 
2002). 
FDA Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials 
for Therapeutics in Adult Healthy Volunteers. US Dept of Health and Human Services, Food 
and Drug Administration, Center for Drug Evaluation and Research. 06 July 2005. Publication 
No. 5541. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. First-in-human study with ACT-
539313, a novel selective orexin-1 receptor antagonist. Br J Clin Pharmacol. 2020 
Jul;86(7):1377-1386. doi: 10.1111/bcp.14251. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. Multiple-dose clinical pharmacology 
of the selective orexin-1 receptor antagonist ACT-539313. Prog Neuropsychopharmacol Biol 
Psychiatry. 2021 Jun 8;108:110166. doi: 10.1016/j.pnpbp.2020.110166.  
Salvadore G, Bonaventure P, Shekhar A, Johnson PL, Lord B, Shireman BT, Lebold TP, 
Nepomuceno D, Dugovic C, Brooks S, Zuiker R, Bleys C, Tatikola K, Remmerie B, Jacobs 
GE, Schruers K, Moyer J, Nash A, Van Nueten LGM, Drevets WC. Translational evaluation 
of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for 
panic in rodents and humans. Transl Psychiatry. 2020 Sep 7;10(1):308. doi: 10.1038/s41398-
020-00937-9. 
 


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CONFIDENTIAL 
Appendix A Schedule of Study Procedures 


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CONFIDENTIAL 
SAD Cohorts 1, 2, 4, 5 
 
Screening 
Check-in Dosing & Observation Discharge (a) 
Outpatient 
Visit 
Early 
Termination  
Follow-up  
Study Day:  
-28 to -2  
Day -1  
Day 1 Day 2 
Day 3 
Day 4 
Day 8 
Day 14 (±2) (b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Demographics and medical history 
X 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 
Abbreviated Neuro Exam 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination  
X 
X 
 
 
 
X  
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight, height, and BMI (d) 
X 
X 
 
 
 
X 
X 
X 
 
Urine drug & cotinine screen 
X 
X 
 
 
 
 
 
 
 
Concomitant medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical conditions 
X 
X 
 
 
 
 
 
 
 
Clinical laboratory tests (f) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hepatitis panel and HIV antibody test 
X 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
Serum Pregnancy test (hCG)  
X 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
 
X 
 
 
 
 
 
 
 
CV Telemetry (n) 
 
 
X 
X 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
X 
 
PGx DNA sample collection (i) 
 
 
X 
 
 
 
 
 
 
PGx RNA collection (j) 
 
 
X 
 
 
 
 
 
 
PK blood collection (k) 
 
 
X 
X 
X 
X 
 
X 
 
Standardized pre-dose meal (S3 fed 
cohorts only) 
 
 
X 
 
 
 
 
 
 


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CONFIDENTIAL 
 
PGx=pharmacogenomic. 
(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must 
then be brought back to the clinic for re-evaluation per the investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose 
[within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at 
Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood 
pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, 
Day 8, Early Termination (if applicable), and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional 
tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to enable additional, retrospective analyses as 
needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and 
then every 12 hours until 48 hours post-dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample (6 mL) will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) 2.5 mL whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be 
collected during the food effect period. 
(k) Blood samples (6 mL) for PK analyses will be collected at time points indicated in Table 7. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
 
 
 
Study drug dosing 
 
 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 


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CONFIDENTIAL 
Cohort 3 SAD 
 Fasted-Fed Crossover 
 
Screening 
Dosing and 
Observation  
Inpatient 
D/C 
 
Inpatient 
No sooner than +14 days or 4 
half-lives of Day 8 visit 
 
 
+4 days 
post 
D/C 
E/T 
Follow-up 
Study Day:  
Days -28 
to -2  
Day 
-1  
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
8 
Day 
-1 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 14 (±2) (b) 
Informed consent 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Admitted to the Clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Abbreviated Neuro Exam 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination  
X 
X 
 
 
 
X  
X 
X 
 
 
 
X  
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight, height, and BMI (d) 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
 
Urine drug & cotinine screen 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Concomitant medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical conditions 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Clinical laboratory tests (f) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Hepatitis panel and HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy test (hCG)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
CV Telemetry (n) 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
PGx DNA sample collection (i) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PGx RNA collection (j) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PK blood collection (k) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 
Lumbar puncture & CSF collection (k) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Standardized pre-dose meal  
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 


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CONFIDENTIAL 
*S3 Cohort will return no sooner than Day 14 or 4 half-lives (whichever is greater) after Day 8 for the Fed portion. The Fed portion will commence on Day -1 
will all the same schedule of events with the exception of dosing will be post-meal.  
PGx=pharmacogenomic. 
(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must 
then be brought back to the clinic for re-evaluation per the investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose 
[within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at 
Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood 
pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, 
Day 8, Early Termination (if applicable), and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional 
tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to enable additional, retrospective analyses as 
needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and 
then every 12 hours until 48 hours post-dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample (6 mL) will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) 2.5 mL whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be 
collected during the food effect period. 
(k) Blood samples (6 mL) for PK analyses will be collected at time points indicated in Table 7. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
 
 
Study drug dosing 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discharged from Clinic 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 


CVN766 
 
Study No. CVN766-101 
Page 75 of 79
Clinical Protocol  - Final  Version 2.0 
October  2021
 
CONFIDENTIAL 
Multiple-Dose 
Regimen Cohorts 
SCR 
 
Check-
in 
 
Inpatient 
Dosing & Observation 
 
Inpatient 
Discharge 
(a) 
 
Outpatient Visit 
E/
T Follow-up 
 
Study Day:  
Days 
-28 to -2  Day -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day  
5 
 (model for 
additional 
dosing days) 
Day  
6 
Day of 
last dose 
 (e.g. 
Day7) 
1 day 
after last 
dose (e.g. 
Day 8) 
2 days after 
last dose 
(e.g. 
Day 9) 
3 days 
±0 after 
last dose 
(e.g.  
Day 10) 
(o) 
7 days ±1 after 
last dose (e.g.  
Day 14) 
 
14 days ±2 
after last 
dose (e.g. 
Day 21 ±2) 
(b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviated neuro exam 
 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Physical examination  
X 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Weight, height, and 
BMI (d) 
X 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Urine drug & cotinine 
screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical 
conditions 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory tests 
(f) 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
 
Hepatitis panel 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy test 
(hCG)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 


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CVN766 
 
Study No. CVN766-101 
Page 77 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
PGx=pharmacogenomic (a) Events listed as occurring at “Inpatient Discharge” visit will occur on that day prior to formal “Inpatient Discharge” but not 
necessarily at the time of Discharge. 
(b) The Follow-up Visit will occur by telephone on Day 21 (±2) unless abnormal CS findings were observed upon discharge. In these cases, subjects must then 
be brought back to the clinic for re-evaluation per Investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 and Day 7 
(pre-dose [within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), Days 2 through 6 (pre-dose and 12 hours post-dose), 
Day 8, Day 9, Early Termination (if applicable), and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood pressure and 
heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Days 1 through 8, Day 9, 
Early Termination (if applicable), and as appropriate at the Follow-up Visit Day 21 (±2 days). Hormone laboratory tests (PRL, thyrotropin [TSH], and FT4) will 
be collected on Days 1 and 7 (morning [fasting] and 3 hours after dosing), Day 9, and Day 14 under fasted conditions. Fasting lipase tests will be collected at 
Day -1, Days 2, 7, and 8 (pre-dose). An additional tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to 
enable additional, retrospective analyses as needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Screening, Inpatient Check-in (Day -1), Days 1 and 7 (pre-dose [within 1 hour prior to dosing], and at 
0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), Days 2 through 6 (pre-dose and 12 hours post-dose), Days 8 and 9, Early Termination (if applicable), and as 
appropriate at the Follow-up Visit Day 21 (±2 days). 
(i) One blood sample (6 mL) will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) 2.5 mL whole blood samples will be collected on Day 1 and Day 7 (pre-dose, 8- and 24-hours post-dose) for RNA pharmacogenomic analysis.  
(k) Blood samples (6 mL) for PK analyses will be collected at time points indicated in Table 8.  CSF samples (up to 10 mL) will be collected at 3 h post-dose by 
lumbar puncture only in cohorts M1 and M2, as indicated in Table 10. Cohort M3 also may, at SRG discretion, undergo PK sampling from CSF, the choice of 
day and sampling time to be decided by SRG. 
(l) PTEs will be collected from signing of ICF up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) 24-hour urine collection is only done for cohort M1, predose and over 24 hours 
(o) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the Day 10 visit is not necessary. 
 
 


CVN766 
 
Study No. CVN766-101 
Page 78 of 79
Clinical Protocol  - Final  Version 2.0 
October  2021
 
CONFIDENTIAL 
Appendix B Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations.  
The Investigator agrees to assume the following responsibilities. 
1. Conduct the study in accordance with the protocol. 
2. Personally conduct or supervise the staff who will assist in the protocol. 
3. Ensure that study-related procedures, including study-specific (non-routine/nonstandard 
panel) screening assessments, are NOT performed on potential subjects prior to the receipt of 
written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed 
of these obligations. 
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conforms 
to local regulatory requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity and 
all anticipated risks to subjects. Make at least yearly reports on the progress of the study to 
the IRB/IEC and issue a final report within 3 months of study completion. 
7. Ensure that requirements for informed consent, as outlined in local regulations, are met. 
8. Obtain valid ICF from each subject who participates in the study and document the date of 
consent in the subject’s medical chart. Valid informed consent is the most current version 
approved by the IRB/IEC. Each ICF should contain a subject authorization section that 
describes the uses and disclosures of a subject’s personal information (including personal 
health information) that will take place in connection with the study. If an ICF does not 
include such a subject authorization, then the Investigator must obtain a separate subject 
authorization form from each subject or the subject’s legally acceptable representative. 
9. Prepare and maintain adequate case histories of all persons entering into the study, including 
eCRFs, hospital records, laboratory results, etc., and maintain these data for a minimum of 
2 years following notification by the sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The Investigator should 
contact and receive written approval from the sponsor before disposing of any such 
documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor.  
12. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours. 


CVN766 
 
Study No. CVN766-101 
Page 79 of 79
Clinical Protocol – FINAL2.0 
October 2021
 
CONFIDENTIAL 
Appendix C Investigator Consent to Use of Personal Information  
Cerevance will collect and retain personal information of Investigator, including his or her name, 
address, and other personally identifiable information. In addition, Investigator’s personal 
information may be transferred to other parties located in countries throughout the world (e.g., 
the United Kingdom, United States, and Japan), including the following: 
• Cerevance, its affiliates, and licensing partners 
• Business partners assisting Cerevance, its affiliates, and licensing partners 
• Regulatory agencies and other health authorities 
• IRBs and IECs 
• Investigator’s personal information may be retained, processed, and transferred by Cerevance 
and these other parties for research purposes, including the following: 
• Assessment of the suitability of Investigator for the study and/or other clinical studies 
• Management, monitoring, inspection, and audit of the study 
• Analysis, review, and verification of the study results 
• Safety reporting and pharmacovigilance relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may 
contain the same chemical compound present in the study medication 
• Inspections and investigations by regulatory authorities relating to the study 
• Self-inspection and internal audit within Cerevance, its affiliates, and licensing partners 
• Archiving and audit of study records 
• Posting Investigator site contact information, study details, and results on publicly accessible 
clinical trial registries, databases, and websites 
• Investigator’s personal information may be transferred to other countries that do not have 
data protection laws that offer the same level of protection as data protection laws in the 
Investigator’s own country. 
• Investigator acknowledges and consents to the use of his or her personal information by 
Cerevance and other parties for the purposes described above. 
 


CVN766 
 
Study No. CVN766-101 
Page 1 of 78
Clinical Protocol  - Version 3.0 
26 November  2021
 
CONFIDENTIAL 
 
 
 
 
PROTOCOL 
 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, 
Tolerability, and Pharmacokinetic Study of Escalating Single and 
Multiple Doses of CVN766  
in Healthy Subjects  
 
 
 
Short Title: Phase 1 SAD/MAD Study of CVN766 
 
Sponsor: 
Cerevance Gamma, Inc. 
One Marina Park Drive, Suite 1410 
Boston, MA 02210 
 
Study Number: 
CVN766-101 
IND Number: 
Not Applicable 
EudraCT Number: 
Not Applicable 
Compound: 
CVN766 
Protocol Version:  
3.0, Amendment 2 
Date: 
26 November 2021 
CONFIDENTIAL PROPERTY OF CEREVANCE 
This document is a confidential communication of Cerevance Gamma, Inc. (“Cerevance”). Acceptance of this 
document constitutes the agreement by the recipient that no information contained herein will be published or 
disclosed without written authorization from Cerevance except to the extent necessary to obtain informed consent 
from those persons to whom the drug may be administered. Furthermore, the information is only meant for review 
and compliance by the recipient, their staff, and applicable institutional review committee and regulatory agencies to 
enable the conduct of the study. 


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CVN766 
 
Study No. CVN766-101 
Page 4 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
INVESTIGATOR AGREEMENT  
I confirm that I have read and that I understand this protocol, the Investigator’s Brochure, and any 
other product information provided by the sponsor. I agree to conduct this study in accordance 
with the requirements of this protocol and also to protect the rights, safety, privacy, and well-being 
of study subjects in accordance with the following: 
• The ethical principles that have their origin in the Declaration of Helsinki 
• International Council on Harmonisation, E6 GCP: Consolidated Guideline 
• All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations 
• Regulatory requirements for reporting serious adverse events (SAEs) are defined in Section  
9.9 of this protocol 
• Terms outlined in the Clinical Study Site Agreement 
• Appendix B – Responsibilities of the Investigator 
 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix C of this protocol. 
Signature of Investigator 
Date 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State/Provence) 
Location of Facility (Country) 
 


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CVN766 
 
Study No. CVN766-101 
Page 6 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
8.1 
Study Medication and Materials ..................................................................................32 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling ......................................32 
8.1.2 Drug Storage ..........................................................................................................33 
8.1.3 Dose and Regimen .................................................................................................33 
8.1.4 Overdose ................................................................................................................34 
8.2 
Investigational Drug Assignment and Dispensing Procedures ....................................35 
8.3 
Randomization Code Creation and Storage .................................................................35 
8.4 
Investigational Drug Blind Maintenance .....................................................................35 
8.5 
Unblinding Procedure ..................................................................................................35 
8.6 
Accountability and Destruction of Sponsor-Supplied Drugs .......................................36 
9.0 
STUDY PLAN ...................................................................................................................37 
9.1 
Study Procedures .........................................................................................................37 
9.1.1 Informed Consent Procedure .................................................................................37 
9.1.2 Demographics, Medical History, and Medication History Procedure ...................37 
9.1.3 Physical Examination Procedure ...........................................................................37 
9.1.4 Weight, Height, and BMI.......................................................................................38 
9.1.5 Vital Sign Procedure ..............................................................................................38 
9.1.6 Documentation of Concomitant Medications ........................................................38 
9.1.7 Documentation of Concurrent Medical Conditions ...............................................39 
9.1.8 ECG Procedure ......................................................................................................39 
9.1.9 Pharmacogenomic Sample Collection ...................................................................39 
9.1.10 PK Sample Collection ............................................................................................41 
9.1.11 PK Parameters ........................................................................................................42 
9.1.12 Procedures for Clinical Laboratory Samples .........................................................43 
9.1.13 Contraception and Pregnancy Avoidance Procedure .............................................45 
9.1.14 Pregnancy ...............................................................................................................46 
9.1.15 Documentation of Screen Failure ..........................................................................46 
9.1.16 Documentation of Randomization .........................................................................47 
9.2 
Monitoring Subject Treatment Compliance .................................................................47 
9.3 
Schedule of Observations and Procedures ...................................................................47 
9.3.1 Screening................................................................................................................47 
9.3.2 Inpatient Check-In .................................................................................................47 
9.3.3 Final Visit (discharge day from clinic) ..................................................................48 
9.3.4 Early Termination ..................................................................................................48 
9.3.5 Follow-up Visit ......................................................................................................48 
9.4 
Biological Sample Retention and Destruction .............................................................48 
9.5 
Blood Volume ..............................................................................................................49 
9.6 
CSF Volume.................................................................................................................49 


CVN766 
 
Study No. CVN766-101 
Page 7 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
9.7 
Definitions....................................................................................................................49 
9.7.1 PTE ........................................................................................................................49 
9.7.2 AE ..........................................................................................................................49 
9.7.3 Additional Points to Consider for PTEs and AEs ..................................................49 
9.7.4 SAEs ......................................................................................................................51 
9.7.5 Severity of PTEs and AEs......................................................................................52 
9.7.6 Causality of AEs ....................................................................................................52 
9.7.7 Relationship to Study Procedures ..........................................................................52 
9.7.8 Start Date ...............................................................................................................52 
9.7.9 Stop Date ................................................................................................................53 
9.7.10 Frequency ...............................................................................................................53 
9.7.11 Action Concerning Study Medication ...................................................................53 
9.7.12 Outcome .................................................................................................................53 
9.8 
Procedures ....................................................................................................................54 
9.8.1 Collection and Reporting of AEs ...........................................................................54 
9.8.2 Collection and Reporting of SAEs .........................................................................55 
9.8.3 Reporting of Abnormal LFT ..................................................................................55 
9.9 
Follow-up of SAEs ......................................................................................................55 
9.9.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities .....56 
10.0 
STUDY-SPECIFIC COMMITTEES .................................................................................57 
11.0 
DATA HANDLING AND RECORDKEEPING ..............................................................58 
11.1 
CRFs (Electronic) ........................................................................................................58 
11.2 
Record Retention .........................................................................................................58 
12.0 
STATISTICAL METHODS ..............................................................................................60 
12.1 
Statistical and Analytical Plans ....................................................................................60 
12.1.1 Analysis Sets ..........................................................................................................60 
12.1.2 Analysis of Demographics and Other Baseline Characteristics ............................60 
12.1.3 PK Analysis ...........................................................................................................60 
12.1.4 Safety Analysis ......................................................................................................61 
12.2 
Interim Analysis and Criteria for Early Termination ...................................................61 
12.3 
Determination of Sample Size .....................................................................................62 
13.0 
QUALITY CONTROL AND QUALITY ASSURANCE .................................................63 
13.1 
Study-Site Monitoring Visits .......................................................................................63 
13.2 
Protocol Deviations ......................................................................................................63 
13.3 
Quality Assurance Audits and Regulatory Agency Inspections ..................................64 
14.0 
ETHICAL ASPECTS OF THE STUDY ...........................................................................65 
14.1 
IRB and/or IEC Approval ............................................................................................65 
14.2 
Subject Information, Informed Consent, and Subject Authorization ..........................66 


CVN766 
 
Study No. CVN766-101 
Page 8 of 78
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26 November 2021
 
CONFIDENTIAL 
14.3 
Subject Confidentiality ................................................................................................67 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy ..................................67 
14.4.1 Publication and Disclosure ....................................................................................67 
14.4.2 Clinical Trial Registration ......................................................................................68 
14.4.3 Clinical Trial Results Disclosure ...........................................................................68 
14.5 
Insurance and Compensation for Injury .......................................................................68 
15.0 
REFERENCES ..................................................................................................................69 
 
LIST OF IN-TEXT TABLES 
Table 1 
Single-Dose Visit Schedule ...................................................................................21 
Table 2 
Multiple Dose Visit Schedule ................................................................................22 
Table 3 
Prohibited Medications and Dietary Products .......................................................29 
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo .......................32 
Table 5 
Planned Single and Multiple Dose Levels by Cohort ............................................34 
Table 6 
Collection of Blood Samples for PK Analysis in Single-Dose Cohorts ................41 
Table 7 
Collection of Blood Samples for PK Analysis in Multiple-Dose Cohorts ............41 
Table 8 
Collection of CSF Samples for PK Analysis in Single-Dose Cohorts ...................42 
Table 9 
Collection of CSF Samples for PK Analysis in Multiple-Dose Cohorts ...............42 
Table 10 
Clinical Laboratory Tests .......................................................................................43 
Table 11 
Medically Significant AE List (categorized as Serious Adverse Events) ..............52 
Table 12 
Windows for PK Blood Sample Collection ...........................................................63 
 
LIST OF IN-TEXT FIGURES 
Figure 1 
CVN766-101 Study Schematic ..............................................................................20 
LIST OF APPENDICES 
Appendix A: Schedule of Study Procedures ..................................................................................70 
 


CVN766 
 
Study No. CVN766-101 
Page 9 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
2.0 
STUDY SUMMARY 
Name of Sponsor(s): 
Cerevance, Inc. 
Compound: 
Title of Protocol: A Phase 1, Randomized, Double-Blind, 
Placebo-Controlled, Safety, Tolerability, and 
Pharmacokinetic Study of Escalating Single and Multiple 
Doses of CVN766 in Healthy Subjects  
IND No.:  
EudraCT No.: 
Not Applicable 
Study Number: CVN766-101 
Phase: 1 
Study Design: 
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in 
healthy subjects with concurrent PK sampling from blood plasma, urine, and cerebrospinal fluid. The overall study 
design is outlined below: 
  
Part 1: Single-Dose Regimen and Fasted-Fed Crossover 
For the single-dose regimen, approximately 40 healthy male or female subjects will be enrolled in 1 of 5 single-dose 
cohorts (designated as S1 through S5, respectively) in an ascending fashion. Each cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a single oral dose of CVN766 suspension, and 
2 subjects will receive a matching placebo suspension under overnight fasted conditions. Subjects will remain fasted 
for 4 hours post-dose. Consumption of water is permitted as desired except for 1 hour before and after administration 
of Study Drug. Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in each 
cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 or placebo to the 
remainder of subjects within the cohort. After blinded review by the Investigator of 24-hour post-dose adverse event 
listings (as applicable) from the sentinel group, the Investigator will advise the sponsor on acceptability to enroll the 
remaining 6 subjects in each cohort. In the event that a safety signal emerges in the sentinel group, a Safety Review 
Group (SRG) meeting may be required as requested by Investigator or Sponsor. To accommodate the lumbar 
puncture in the S3 fasted cohort, the remaining 6 subjects dosing may be staggered every two days after the sentinel 
group. The planned dose levels will be 5, 15, 45, 125, and 250 mg CVN766.  The SRG will review all available 
blinded safety, tolerability, clinical laboratory results (minimally including samples collected from subjects through 
72-hours post-dose), and pharmacokinetic (PK) data after each cohort and before subsequent dose escalation. Each 
following dose level may be higher, lower, or remain the same as the preceding cohort, dependent on the 
recommendation of the SRG.  
Additional cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety and tolerability 
of CVN766. For example, if cohort S5 is well-tolerated, additional cohorts with higher dose levels may be 
considered. Such additional cohorts will follow the same schedule of events as for cohorts S1 through S5. 
Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary to fully 
characterize the PK profile of CVN766. 


CVN766 
 
Study No. CVN766-101 
Page 10 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
To assess the effect of food on CVN766 bioavailability in suspension formulation, the single-dose administration 
will be repeated in a single cohort (S3) after ingestion of a standardized high-fat, high-calorie meal according to 
FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Dec 2002). Once the safety 
of the S3 cohort dose level has been assessed, the S3 cohort subjects will return to the clinic (no sooner than 14 days 
after their prior dose, or at least 4 half-lives, has lapsed based on preliminary PK data, whichever is longer). They 
will receive the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish at 
least approximately 85% of their breakfast within 30 minutes and receive an investigational product 30 minutes (± 
5 minutes) after beginning the meal. Sentinel dosing will not be required for subjects returning to the clinic for the 
fed regimen. If the CVN766 PK parameters in the fasted S3 cohort reveal poor absorption with inconclusive results, 
the fed cohort will be deferred until a higher dose level.    
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit for safety and 
PK assessments. On Day 1, subjects will undergo safety monitoring and PK sampling from blood plasma through 
72 hours post-dose and, for cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. The total 
confinement period will be 4 nights, unless extended at the discretion of the Investigator, e.g., for monitoring and/or 
management of AEs. Follow-up assessments will occur on approximately Days 8 and 14 and +21 and +28 for cohort 
S3. 
A summary of the single-dose regimen visit schedule is presented below:  
Screening a 
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b 
Inpatient PK,  
Safety and 
Lumbar 
Puncture Site 
Assessments 
(S3 fasted) 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
 
Day -28 to -2 
Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14 
±2 days 
 
(a) Screening will occur at study entry. S3 subjects returning for the “Fed” repetition of the single-dose 
regimen will not undergo Screening assessments except as required at Day -1. 
(b) CSF collection will apply only to cohort S3 (fasted). 
(c) Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs. 
(d) The final follow-up assessment will occur by telephone unless abnormal, clinically significant (CS) 
findings were observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
 
Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 healthy male and female subjects aged 18 to 55 will be enrolled 
in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. The dose 
levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-dose cohorts 
M1 through M3, respectively. Each multiple-dose cohort will consist of 8 subjects randomized to CVN766 or 
placebo, whereby 6 subjects will receive a daily oral dose of CVN766, and 2 subjects will receive matching placebo 
for 7 days. Dosing will be administered in the fasting state; the SRG can change this if exposure is higher in the fed 
state. The planned dosing duration for the multiple-dose cohorts is 7 days. However, the duration may be increased 
to ≤14 days at the discretion of the SRG if preliminary PK data suggest steady-state will not be achieved within 6 
days of daily dosing. For each dose on intensive PK sampling days (first and last days of dosing, e.g., Days 1 and 
7), subjects will remain fasted for 4 hours post-dose. On other dosing days (Days 2-6), subjects will remain fasted 
for 1-hour post-dose. Consumption of water is permitted as desired except for 1 hour before and after administration 
of Study Drug. Unlike the single-dose regimen, sentinel dosing within cohorts is not required in the multiple-dose 
regimen. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all safety, tolerability, and 
clinical laboratory results for the fasting drug administration to single-dose Cohort S3 (minimally including samples 
collected through Day 4) and available PK data. For each multiple-dose cohort after the first, the actual choice of 


CVN766 
 
Study No. CVN766-101 
Page 11 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
dose level may be modified by the SRG after the available blinded safety, tolerability, clinical laboratory results, 
and PK data in the preceding multiple-dose and corresponding single-dose cohorts (i.e., multiple-dose Cohort M2 
will not initiate until the data review for multiple-dose Cohort M1 and single-dose cohort S4 is complete). Each 
subsequent dose level may be higher, lower, or remain the same as the preceding. 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety 
and tolerability of CVN766. Such additional cohorts will follow the same schedule of events as for prior multiple-
dose cohorts.  Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary 
to fully characterize the PK profile of CVN766. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit 
for the duration of the dosing period and for at least 48 hours after the last dose for safety and PK assessments before 
discharge. On treatment Days 1 and 7, subjects will undergo safety monitoring and PK sampling from blood plasma 
through 48 hours post-dose and, in cohort M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, 
on treatment Day 7 (or last day of dosing, if extended beyond Day 7), subjects will additionally undergo PK sampling 
from CSF via lumbar puncture at 3 hours post-dose. If needed to resolve questions arising from prior cohorts’ data, 
subjects in cohort M3 also may, at SRG discretion, undergo PK sampling from CSF via lumbar puncture, the choice 
of day (e.g., Day 1 or Day 7) and sampling time to be decided by SRG. Subjects in MAD cohorts may be asked to 
return to the clinic for an additional PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK 
data, i.e., t½). The total confinement period will be 9 nights unless extended for additional dosing days or 
management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final dose. 
A summary of the multiple-dose regimen visit schedule is presented below: 
Screening 
Inpatient  
Check-in 
Dosing, PK, 
CSF, & Safety 
Assessments  a 
PK / Safety 
Assessments & 
inpatient 
discharge b 
Follow-Up Outpatient 
Visits c 
Follow-Up Call d 
Day -28 to -2 
Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g., 
Days 8-9) 
3 days ±0 after last dose 
(e.g., Day 10) & 
7 days ± 1 after last dose 
(e.g., Day 14) 
14 days ±2 after last 
dose (e.g., Day 21) 
(a) CSF sampling will occur on Day 7 in cohorts M1 and M2. Cohort M3 also may, at SRG discretion, undergo 
PK sampling from CSF, the choice of day and sampling time to be decided by SRG.  
(b) Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or, if 
necessary, to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after last dose (e.g., Day 
10) may be omitted at Investigator’s discretion. 
(d) The Follow-up Visit will occur by telephone unless abnormal, clinically significant (CS) findings are 
observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to ≤14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in cohort M1. 
Safety Review Group (SRG) 
The SRG will be comprised of the Investigator, Medical Monitor, Cerevance Responsible Medical Officer and may 
include other Cerevance representatives. A pharmacokineticist and other subject matter experts may participate as 
needed. The SRG will be responsible for ongoing review of safety, tolerability, and clinical laboratory results, and 
available PK data and deciding: 
1. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in single-
dose cohorts (based on a review of available data including at least 72 hours post-dose safety data and 
clinical laboratory results from each of the subjects in the current cohort),  
2. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in 
multiple-dose cohorts (based on a review of available data including at least 48 hours post 7th dose safety 
data from each of the subjects in the current cohort), 


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CVN766 
 
Study No. CVN766-101 
Page 13 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
Subjects have a known hypersensitivity to any component of the formulation of CVN766. Subjects have evidence 
of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, 
urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, psychiatric disorder, or other 
abnormality that may impact the ability of the subject to participate or potentially confound the study results. Any 
finding in the subject’s medical history, physical examination, or safety laboratory tests gives reasonable suspicion 
of a condition that might interfere with the conduct or interpretation of the study.  
A complete list of exclusion criteria is provided in Section 7.2.  
In addition, subjects may not use any excluded medications (including oral contraceptives as listed in Table 3), 
supplements, or food products. Concomitant medications and dietary products to be excluded are listed in Table 3. 
Main Criteria for Evaluation and Analyses: 
- Safety:  
Safety parameters will include AEs, clinical laboratory results, vital signs, physical examinations, electrocardiogram 
(ECG). AEs will be collected from signing the informed consent form (ICF) up until dosing on Day 1 as pretreatment 
events (PTEs), and any event that occurs from dosing until 14 days after the last dose will be captured as an AE. 
Vital signs will be recorded at Screening, Inpatient Check-in (Day -1), and throughout the dosing period. Vital signs 
will include tympanic body temperature measurement, blood pressure, respiration rate, and pulse (beats per minute 
[bpm]). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day 
-1) 15 minutes apart (the average will be used to determine eligibility). Heart rate and blood pressure will be 
measured after at least 5 minutes supine and again at 2 minutes after standing for all scheduled timepoints.  
Standard 12-lead ECGs will be recorded at Screening, Inpatient Check-in (Day -1), and periodically throughout the 
dosing period. Triplicate ECGs will be taken at each timepoint. 
A complete list of safety assessments is provided in Section 9.11, and the full Schedule of Study Procedures is 
provided in Appendix A. 
- PK:  
The plasma PK parameters are used as PK endpoints to determine drug exposure at each dose and facilitate dose 
escalations.  
Plasma samples will be collected for the determination of concentrations of CVN766 throughout the study as 
prescribed in the Schedule of Study Procedures (Appendix A). Cerebrospinal fluid (CSF) samples will be collected 
for the determination of concentrations of CVN766 as described in Section 9.6 and the Schedule of Study Procedures 
(Appendix A). PK sampling timepoints may be modified or added based on emerging PK data to most appropriately 
characterize the PK profile of CVN766 as determined by the SRG. 
PK parameters of CVN766 will be derived using noncompartmental analysis methods from the concentration-time 
data for all evaluable subjects. Actual sampling times, rather than scheduled sampling times, will be used in all 
computations involving sampling times. The following PK parameters will be determined from concentrations of 
CVN766 in plasma: Cmax, AUC from time 0 to the last quantifiable concentration (AUCt), AUC from time 0 to 
infinity (AUC∞), AUC from time 0 to 24 hours (AUC24), time to reach Cmax (tmax), terminal elimination rate constant 
(λz), terminal elimination half-life (t1/2z), apparent clearance (CL/F), and apparent volume of distribution (Vz/F). 
Multiple-dose PK will also include AUC over the dosing interval (AUCtau), apparent clearance at steady state 
(CL/Fss), apparent volume of distribution at steady state (Vz/Fss), steady-state nadir concentrations, and 
accumulation ratios  
The PK parameters to be determined from concentrations of CVN766 in CSF will include plasma: CSF ratio 
by time point.  
- Pharmacogenomics: 
One whole blood sample will be collected at pre-dose on Day 1 for pharmacogenomic analysis; this will only be 
collected once per subject. Two whole blood samples will be collected at pre-dose on Day 1 and at multiple 
timepoints post-dose for ribonucleic acid (RNA) pharmacogenomic analysis. The pre-dose RNA blood samples 
should be collected under fasted conditions and prior to any other blood collection. The samples will be stored for 
no longer than 15 years after completion of the CVN766 study and/or until the drug development of CVN766 is no 
longer actively pursued by Cerevance or its collaborators. No samples will be stored for longer than permitted by 
the applicable law, and samples will be destroyed upon notification from Cerevance. “Stored samples” in this context 
are defined as samples that are double coded (the samples are stripped of all personally identifying information, but 


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CVN766 
 
Study No. CVN766-101 
Page 16 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRSD 
maximum recommended starting dose 
NCS 
not clinically significant 
NOAEL 
no-observed-adverse-effect-level 
Ox1R 
orexin 1 receptor 
Ox2R 
orexin 2 receptor 
PK 
pharmacokinetic 
PRL 
prolactin 
PT 
preferred term 
PTE 
pretreatment event 
QTcB 
QT interval with Bazett’s correction method 
QTcF 
QT interval with Fridericia’s correction method 
RNA 
ribonucleic acid 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAD 
single-ascending dose 
SAP 
statistical analysis plan 
SOC 
system organ class 
SRG 
Safety Review Group 
SUSARs 
suspected unexpected serious adverse reactions 
t1/2z 
terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time to reach Cmax 
ULN 
upper limit of normal 
Vz/F 
apparent volume of distribution after extravascular administration 
Vz/Fss 
apparent volume of distribution after extravascular administration at steady state 
WHO 
World Health Organization 


CVN766 
 
Study No. CVN766-101 
Page 17 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
4.0 
INTRODUCTION 
4.1 
Background 
The neuropeptide orexin, also known as hypocretin, is produced exclusively in the orexigenic 
neurons in the hypothalamus. There are two forms of orexin, Orexin-A, and orexin-B, alternatively 
spliced from the same gene, HCRT.   There are two orexin receptors, orexin 1 receptor (Ox1R) 
and orexin 2 receptors (Ox2R), both of which are G-protein coupled receptors. Both orexin-A and 
orexin-B can bind to either receptor, and in each case, agonist binding results in an increase in 
intracellular calcium levels. However, while orexin-A is equipotent at both receptors, orexin-B 
shows a 10-fold selectivity for Ox2R.  
Ox1R is selectively expressed in key brain areas relating to psychiatric disorders. Ox1R-expressing 
neurons in the bed nucleus of the stria terminalis, amygdala, locus coeruleus, raphe nucleus, and 
the ventral tegmental area are important in regulating emotions of stress, anxiety, motivation, and 
reward. CVN766 is a potent and highly selective small-molecule Ox1R antagonist with no 
significant off-target activity. Nonclinical PK and toxicology studies with CVN766 and other 
Ox1R antagonists have established their pharmacological characteristics and probable safety 
profile. 
Ox2R is expressed in some overlapping areas, including the raphe nucleus, ventral tegmental area, 
but also areas important to arousal and sleep regulation, including the tuberomammillary nucleus. 
The widely used sleep aid suvorexant (Belsomra®), approved for use in Australia, is a dual Ox1R 
and Ox2R antagonist, but its sleep-inducing effects are generally attributed to its activity on Ox2R. 
A second dual Ox1R and Ox2R antagonist, lemborexant, appeared safe and effective in clinical 
studies, has been approved in many countries worldwide, and has been submitted for marketing 
authorization in Australia.  
Clinical effects to be expected of a selective Ox1R antagonist remain uncertain. CVN766 has not 
yet been studied in humans. Other selective Ox1R antagonists have reported early-stage human 
clinical trials, notably JNJ-61393215 (ClinicalTrials.gov Identifier: NCT04080752; Salvadore et 
al., 2020) and ACT-539313 (NCT01954589; Kaufmann et al., 2020; Kaufmann et al., 2021). Both 
drugs were well tolerated and deemed safe for investigational use, the most common AEs being 
somnolence and mild headache.   
4.2 
Rationale for the Proposed Study 
CVN766 is a highly selective orexin-1 receptor (Ox1R) antagonist and may have utility as 
treatment for psychiatric disorders including schizophrenia, panic disorder and anxiety, and 
addiction. Its safety and PK profile have been preliminarily established in nonclinical toxicology 
studies. The present study will be the first conducted in humans with CVN766 and will examine 
the compound's safety, tolerability, and PK in healthy subjects. 
Nonclinical pharmacology, toxicity, and pharmacokinetic (PK) studies support the proposed 
escalating single- and multiple-dose study of CVN766 in healthy subjects with a starting dose of 
5 mg. Section 6.2 outlines the justification for the planned dose ranges.  
 


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CVN766 
 
Study No. CVN766-101 
Page 20 of 78
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CONFIDENTIAL 
6.0 
STUDY DESIGN AND DESCRIPTION 
6.1 
Study Design 
This is a phase 1, randomized, double-blind, placebo-controlled, single- and multi-dose ascending 
study in healthy subjects. Figure 1 provides a schematic illustration of the study. 
Figure 1 
CVN766-101 Study Schematic 
 
 
6.1.1 Part 1: Single-Dose Regimen and Fasted-Fed Crossover 
Approximately 40 subjects will be enrolled in 1 of the 5 single-dose cohorts (designated as S1 
through S5, respectively) in an ascending fashion. Dose escalation will only occur after a fully 
blinded review of all available safety, tolerability, clinical laboratory results (minimally including 
samples collected from subjects through 72-hours post-dose), and available PK data, including at 
least a 72-hour follow-up of the most recent cohort. 


CVN766 
 
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The planned dose levels are provided in Table 5. Each cohort will consist of 8 subjects randomized 
to CVN766 or placebo, whereby 6 subjects will receive a single dose of CVN766 and 2 subjects 
will receive a matching placebo under overnight fasted conditions.  
Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in 
each cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 
to the remainder of subjects within the cohort. After blinded review of 24-hour post-dose safety 
and tolerability data, the remaining 6 subjects of each cohort may be dosed provided that the 
adverse event (AE) profile of CVN766 in the first 2 subjects is considered acceptable.  
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the 
unit for safety and PK assessments at least 72 hours after dosing. On Day 1, subjects will undergo 
safety monitoring (including labs, physical exam, neurological exam, cardia telemetry at 12-hours 
pre-dose) and PK sampling from blood plasma through 72 hours post-dose.  In addition, for cohort 
S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. For subjects participating in 
the SAD cohorts, the total confinement period will be 4 nights unless extended for management 
of AEs at the discretion of the Investigator. Follow-up assessments will occur on approximately 
Days 8 and 14. 
To assess the effect of food on bioavailability of CVN766 in suspension formulation, single-dose 
administration will be repeated in a single cohort after ingestion of a standardized high-fat high-
calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed 
bioequivalence studies, Dec 2002). Once the safety of the S3 cohort dose level has been assessed, 
the S3 cohort subjects will return to the clinic (no sooner than 14 days after their prior dose, or at 
least 4 half-lives has lapsed based on preliminary PK data, whichever is longer) and will receive 
the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish 
at least approximately 85% of their breakfast within 30 minutes and will receive an investigational 
product 30 minutes (± 5 minutes) after beginning the meal. Sentinel dosing will not be required 
for subjects returning to the clinic for the fed regimen.  If the CVN766 PK parameters in the fasted 
S3 cohort reveal poor absorption with inconclusive results, the fed cohort will be deferred until a 
higher dose level. 
An outline of the single-dose study visit schedule is included in Table 1. A Schedule of Study 
Procedures is listed in Appendix A. 
Table 1 
Single-Dose Visit Schedule 
Screening a 
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b 
Inpatient PK 
& Safety 
Assessments 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
Day -28 to -2 
Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14  
±2 days 
(a) Screening will occur at study entry. Subjects returning for the “Fed” repetition of the single-dose regimen 
will not undergo Screening assessments except as required at Day -1. 
(b) CSF collection will apply only to cohort S3 (fasted). 
(c) Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs. 
(d) The final follow-up assessment will occur by telephone unless abnormal CS findings are observed upon 
discharge. In these cases, subjects must return to the clinic for re-evaluation. 


CVN766 
 
Study No. CVN766-101 
Page 22 of 78
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6.1.2 Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 subjects will be enrolled in 1 of the 3 multiple-
dose cohorts (designated as M1 through M3, respectively) in an ascending fashion.  Dosing will 
be administered in the fasting state; this can be changed by the SRG if exposure is found to be 
higher in the fed state. The dose levels planned to be studied in the multiple-dose regimen (M1 
through M3) are provided in Table 5. Each multiple-dose cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a daily dose of CVN766, and 
2 subjects will receive matching placebo for 7 days. However, the duration may be increased to 
≤14 days at the discretion of the safety review group (SRG) if preliminary PK data suggest steady-
state will not be achieved within 6 days of daily dosing. Unlike the single-dose regimen, sentinel 
dosing within cohorts is not required in the multiple-dose regimen. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and 
remain in the unit for the duration of the dosing period and for at least 48 hours after the last dose 
for safety and PK assessments before discharge. On treatment Days 1 and 7, subjects will undergo 
safety monitoring and PK sampling from blood plasma through 48 hours post-dose and, in cohort 
M1 only, from urine through 24 hours post-dose. In cohorts M1 and M2, on treatment Day 7 (or 
last day of dosing, if extended beyond Day 7), subjects will additionally undergo PK sampling 
from CSF via lumbar puncture at 3 hours post-dose. If needed to resolve questions arising from 
prior cohorts’ data, subjects in cohort M3 also may, at SRG discretion, undergo PK sampling from 
CSF via lumbar puncture, the choice of day (e.g., Day 1 or Day 7) and sampling time to be decided 
by SRG. Subjects in MAD cohorts may be asked to return to the clinic for an additional plasma 
PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK data, i.e., t½. The 
total confinement period will be 9 nights unless extended for additional dosing days or for 
management of AEs. Follow-up assessments will occur approximately 7 and 14 days after the final 
dose. A summary of multiple-dose study visits is included in Appendix A.  
Table 2 
Multiple Dose Visit Schedule 
Screening 
Inpatient  
Check-in 
Dosing, 
PK, 
CSF, & Safety 
Assessments  a,f 
PK 
/ 
Safety 
Assessments 
& 
inpatient discharge b 
Follow-Up 
Outpatient 
Visits c 
Follow-Up Call d 
Day -28 to -2 
Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g. Days 
8-9) 
3 days ±0 after last dose 
(e.g. Day 10) & 
7 days ± 1 after last dose 
(e.g. Day 14) 
14 days ±2 after 
last dose (e.g. 
Day 21) 
(a) CSF sampling will occur on Day 7 in cohorts M1 and M2. Cohort M3 also may, at SRG discretion, undergo 
PK sampling from CSF, the choice of day and sampling time to be decided by SRG. 
(b) Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or if necessary, 
to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after the last dose (e.g., 
Day 10) may be omitted at Investigator’s discretion. 
(d) The Follow-up Visit will occur by telephone unless abnormal CS findings are observed upon discharge. In 
these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to ≤14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in cohort M1. 


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6.1.3 Dose Escalation  
The SRG will be comprised of the Investigator, Medical Monitor, Cerevance Responsible Medical 
Officer and may include other Cerevance representatives. A pharmacokineticist and other subject 
matter experts may participate as needed. The SRG will be responsible for ongoing review of 
safety, tolerability, clinical laboratory results, and available PK data and deciding to: 
• Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in single-dose cohorts (based on a review of available data including at least 72 
hours post-dose safety data and clinical laboratory results from each of the subjects in the 
current cohort),  
• Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in multiple-dose cohorts (based on a review of available data including at least 48 
hours post 7th dose safety data from each of the subjects in the current cohort), 
• Add additional dose cohort(s) in either the single- or multiple-dose studies, 
• Increase the duration of dosing in the multiple-dose cohorts from 7 days to ≤14 days 
If 2 or more subjects in a single cohort experience the same type of serious or medically adverse 
event, further dosing will be withheld until the SRG investigates the events.  Based on this 
assessment, the SRG will determine if the study should be terminated or continued and whether 
modification of planned dose levels and/or implementation of additional safety monitoring is 
indicated.   
For each cohort (including sentinel subjects, where applicable), the SRG will carefully review the 
available blinded safety, tolerability, clinical laboratory results, and PK data to determine whether 
dosing should stop or continue (and, if continued, at what dose, including whether to repeat the 
previous dose), whether additional sequential dosing should be implemented in future cohorts or 
whether the blind should be broken to identify whether the subjects received CVN766 or placebo. 
However, precautions must be taken not to unblind the study staff, including the investigator. 
If all doses are tolerated, then additional cohorts with higher doses may be considered; The actual 
choice of the subsequent dose level will occur after the full review of the available blinded safety, 
tolerability, clinical laboratory results, and available PK data in the preceding cohort. The 
subsequent dose level may be higher, lower, or remain the same as the preceding dose level. If 
necessary, additional cohort(s) may be added to fully characterize the safety and tolerability of 
CVN766. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all available 
safety, tolerability, and clinical laboratory results for the fasting drug administration to single-dose 
Cohort S3 (minimally including samples collected through Day 4) and available PK data. For each 
multiple-dose cohort after the first, the actual choice of dose level may be modified by the SRG 
after review of the available blinded safety, tolerability, and clinical laboratory results and PK data 
in the preceding multiple-dose and next-higher-dosage single-dose cohorts (i.e., multiple-dose 
Cohort M2 will not initiate until the data review for multiple-dose Cohort M1 and single-dose 
cohort S4 is complete). Each subsequent dose level may be higher, lower, or remain the same as 
the preceding dose level. 


CVN766 
 
Study No. CVN766-101 
Page 24 of 78
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CONFIDENTIAL 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully 
characterize the safety and tolerability of CVN766. Such additional cohorts will follow the same 
schedule of events as for prior multiple-dose cohorts. Additional/Alternative PK timepoints may 
be implemented if the SRG determines this is necessary to fully characterize the PK profile of 
CVN766. 
All AEs reported during the Treatment Period, both within and across cohorts, up to the time of 
discharge, will be evaluated to assess the need for the subject and/or study termination in 
accordance with the prespecified criteria for discontinuation/termination (Section 6.3.1).  
Additionally, the SRG may decide not to escalate the dose for a particular cohort but rather 
administer the same or a lower dose level to the next cohort. Additional/ Alternative PK timepoints 
may be implemented if the SRG determines this is necessary to fully characterize the PK profile 
of CVN766. 
6.2 
Justification for Study Design, Dose, and Endpoints 
The study is double-blind and placebo-controlled to avoid subjective bias in the assessment of the 
safety and tolerability of CVN766. Dose escalation will be predicated on a review of available 
blinded safety, tolerability, and PK data observations for each prior dose cohort.  
The sponsor has selected the starting dose level considering the FDA Guidance for Industry 
(Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult 
Healthy Volunteers, 06 July 2005) and providing additional safety factors to the initial calculations 
based on the principles outlined in the guidance. The toxicity profile of CVN766 after oral dosing 
was examined in repeat dosing studies in rats and dogs. Scaling based on body surface area was 
conducted by multiplying the NOAELs for the most sensitive animal species by the appropriate 
conversion factors. Based on these calculations and applying a 10-fold safety margin below the 
NOAEL human-equivalent dose (HED), the maximum recommended starting dose (MRSD) for 
this first-in-human study is 167 mg for a 60 kg subject. The selected starting dose level is 5 mg. 
The study's multiple-ascending dose (MAD) portion seeks to prepare for subsequent repeat dosing 
studies in subjects. Each MAD dose level will have been studied or exceeded in the SAD portion 
of the study before its use in a MAD cohort.  
Nonclinical toxicity study data provide a basis for calculating the maximum exposure level that 
can be presumed safe. Escalating to the HED of the NOAEL in the most sensitive animal species, 
the maximum dose for clinical use is 1670 mg/day.  
The projected t1/2z in animal species ranged up to 6.5 hours, so sample collection through Inpatient 
Discharge 72 hours post-dose is expected to correspond to more than 5 half-lives and is anticipated 
to be adequate to document elimination of CVN766. The study design allows for collecting 
additional PK samples at later timepoints if preliminary emerging PK results are indicated.  
AEs, physical exams, vital signs, ECG findings, and clinical laboratory results are used as safety 
assessments to determine dose tolerability and dose-limiting effects of CVN766. The plasma PK 
and CSF parameters and PK endpoints will help elucidate the pharmacology of CVN766.  
Samples for DNA analysis will be collected and may be used to evaluate drug metabolic enzyme 
and transporter polymorphisms that may contribute to the variability in the PK of CVN766. 


CVN766 
 
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6.3 
Premature Termination or Suspension of Study or Investigational Site 
6.3.1 Criteria for Premature Termination or Suspension of the Study 
The study will be completed as planned unless new information or other evaluation regarding the 
safety of the study medication indicates an adverse change in the risk profile for the compound, 
such that the SRG or Institutional Review Board (IRB) considers the risk is no longer acceptable 
for subjects participating in the study. 
In addition, if any of the following occur, further dosing will be withheld until the SRG reviews 
the relevant data, including unblinded data (if deemed necessary by the SRG request), and will 
decide whether it is safe to suspend dosing or continue dosing at either the planned or alternative 
dose levels or decides to prematurely terminate the study: 
1. Two or more subjects in any single cohort or across more than 1 cohort experience the same 
type of serious or Medically Significant event as defined by the Investigator 
2. Two or more subjects in any single cohort or across more than 1 cohort experience alanine 
aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations >5 × upper limits 
of normal (ULN) in the absence of a concomitant bilirubin increase (see point 3 below) 
3. One or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN in the presence of a total bilirubin increase >2 ×ULN or an 
international normalized ratio (INR) >1.5 without findings of cholestasis or other alternate 
etiology to explain the elevations (i.e., “Hy’s Law cases”) 
4. Two or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
6.3.2 Criteria for Premature Termination or Suspension of Investigational 
Sites 
A study site may be terminated prematurely or suspended if the site (including the investigator) is 
found in significant violation of Good Clinical Practice (GCP), protocol, or contractual agreement, 
is unable to ensure adequate study performance, or as otherwise permitted by the contractual 
agreement. 
6.3.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s) 
In the event that the sponsor, an IRB/independent ethics committee (IEC), or regulatory authority 
elects to terminate or suspend the study or the participation of an investigational site, a study-
specific procedure for early termination or suspension will be provided by the sponsor; applicable 
investigational sites will follow the procedure during the course of termination or study 
suspension. 


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Study No. CVN766-101 
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CONFIDENTIAL 
7.0 
SUBJECT POPULATION 
Screening for eligible subjects will be performed within 28 days prior to randomization or first 
dose.  
7.1 
Inclusion Criteria 
Subject eligibility is determined according to the following criteria prior to entry into the study: 
1. In the investigator's opinion, the subject can understand and sign the Informed Consent Form 
and comply with all protocol requirements.  
2. The subject is a healthy male or female adult who is 18 to 55 years of age, inclusive at the time 
of ICF. 
3. Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 32.0 kg/m2, inclusive 
at Screening.  
4. A male subject who is nonsterilized* and sexually active with a female partner of childbearing 
potential* agree to use two forms of adequate contraception* from signing the ICF throughout 
the study and for 90 days after the last dose. 
*Definitions and acceptable methods of contraception are defined in 
Section 9.1.13 Contraception and Pregnancy Avoidance Procedure, and 
reporting responsibilities are defined in Section 9.1.14 Pregnancy. 
5. A female subject of childbearing potential who complies with contraception requirements* or 
a female with no childbearing potential, defined as the subject has been surgically sterilized 
(hysterectomy, bilateral oophorectomy, or tubal ligation) or who are postmenopausal (defined 
as continuous amenorrhea of at least 2 years and FSH>40 IU/L).  
Note: hormonal contraceptives are not permitted for female participants, as referenced in Table 
3. Female partners of male participants can use hormonal contraceptives. 
7.2 
Exclusion Criteria 
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. Subject has received any investigational compound within 30 days prior to the first dose of 
study medication or within 5 half-lives, whichever is greater. 
2. Subject is a study site employee or an immediate family member of a study site employee.  
3. Subject has evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic 
disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious 
allergy, full-body allergic skin rash (including hives), psychiatric disorder, evidence of 
abnormal liver function test, evidence of abnormal renal function tests or other abnormality 
that may impact the ability of the subject to participate or potentially confound the study 
results.  
Note: Healthy volunteers with pre-existing stable disease, defined as diseases not requiring 
significant change in therapy or hospitalization for worsening disease during the 6 wks before 
enrolment, may be included at the discretion of the Investigator. 


CVN766 
 
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Page 27 of 78
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CONFIDENTIAL 
4. There is any finding in the subject’s medical history, physical examination, or safety laboratory 
tests giving reasonable suspicion of a disease that would contraindicate taking CVN766 or a 
similar drug in the same class or that might interfere with the conduct of the study 
5. Subject has a known hypersensitivity to any component of the formulation of CVN766. 
6. Subject has a positive urine result for drugs of abuse at Screening or Inpatient Check-in (Day -
1). 
7. Subject has a history of a major psychiatric illness or currently receiving therapy for a 
psychiatric condition 
8. Subject has a history of drug abuse or a history of alcohol abuse (more than 14 units/week) 
within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and 
drugs throughout the study. 
9. Subject has taken any excluded medication, supplements, or food products listed in the 
Excluded Medications and Dietary Products table as listed in Table 3. 
10. Male subjects who do not agree to all the following rules: when sexually active with a female 
partner(s) of childbearing potential during the study, and for 90 days after the last dose of study 
drug: a) must use two acceptable methods of birth control (condom or surgical sterilization 
combined with highly effective method of contraception for the female partner) and b) refrain 
from sexual activity with female partners who do not use an acceptable method of birth control. 
Barrier contraception (condom) must be used by all-male subjects who were not surgically 
sterilized at least 90 days prior to screening. Male subjects must also agree to refrain from 
sperm donation during the study and until 90 days after the last dose of the study drug. 
11. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova 
during the study or 30 days after the last dose of the study drug. Women of childbearing 
potential must agree to practice an acceptable method of birth control (e.g., intrauterine device, 
barrier, abstinence).  
Note: hormonal contraceptives are not permitted for female participants, as referenced in Table 
3. Female partners of male participants can use hormonal contraceptives. 
*Definitions and acceptable methods of contraception are defined in Section 9.1.13. 
Contraception and Pregnancy Avoidance Procedure and reporting responsibilities are 
defined in Section 9.1.14 Pregnancy. 
12. Subject has previously had a seizure or convulsion (lifetime, with the exception of febrile 
seizures), including absence seizure. 
13. Subject has current o recent (within 6 months) gastrointestinal disease that would be expected 
to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention 
known to impact absorption [e.g., bariatric surgery or bowel resection], esophageal reflux, 
peptic ulcer disease, erosive esophagitis, or frequent [i.e., more than once per week] occurrence 
of heartburn). 
14. Subject has a history of cancer or other malignancy, except for basal cell carcinoma or 
squamous cell carcinoma that has been in remission for at least 3 years prior to Day 1. 


CVN766 
 
Study No. CVN766-101 
Page 28 of 78
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CONFIDENTIAL 
15. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody, or a human immunodeficiency virus infection at Screening. 
16. Subject who regularly use nicotine-containing products (including but not limited to cigarettes, 
electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). The 
casual users (≤ 10 cigarettes/week)  may participate but must agree to refrain from the time of 
Screening for the duration of the study or a positive urine cotinine test at Inpatient Check-in 
(Day -1). 
17. Subject has poor peripheral venous access (defined as more than three failed attempts to 
cannulate. 
18. Subject has donated or lost 450 mL or more of their blood volume (including plasmapheresis) 
or had a transfusion of any blood product within 45 days prior to Day 1. 
19. Subject has an abnormal (CS) ECG at Screening or Inpatient Check-in (Day -1). Entry of any 
subject with an abnormal (NCS) ECG must be approved and documented by signature by the 
Investigator or medically qualified sub-investigator.  
20. Subject has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 
40 to 90 mm Hg for diastolic, confirmed with repeat per PI discretion, at the Screening Visit 
or Inpatient Check-in (Day -1). 
21. Subject has a resting heart rate outside the range of 40 to 100 bpm, confirmed with repeat per 
PI discretion, at the Screening Visit or Inpatient Check-in (Day -1). 
22. Subject has a QT interval with Fridericia’s correction method (QTcF) >450 ms (males) or 
>470 ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat testing 
at the Screening Visit or Inpatient Check-in (Day -1) Visit. 
23. Subject has abnormal Screening or Inpatient Check-in (Day -1) laboratory values that suggest 
a CS underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 
the ULN, confirmed with one repeat testing. 
24. Subject has a risk of suicide according to the investigator’s clinical judgment or has made a 
suicide attempt in the previous 2 years. 
7.3 
Excluded Medications and Dietary Products 
Use of the agents in Table 3 (prescription or nonprescription) is prohibited from the time points 
specified until completion of all study activities. 


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Table 3 
Prohibited Medications and Dietary Products 
 
CYP= cytochrome P-450, OTC=over the counter. 
(a) Occasional use of acetaminophen (~1 g/day) and 400mg ibuprofen TDS when required or other medication as 
approved by the sponsor’s Medical Monitor on a case-by-case basis is allowed except on Day 1 
(b) Inclusive of but not limited to H1N1 and flu vaccinations. Subjects who have received the COVID-19 Vaccine 
between -10 and -28 days may participate provided they did not experience any side effects of any description. 
COVID-19 vaccine doses may be administered 7 days post-study medication dosing.  
(c) e.g., chloramphenicol, clarithromycin, ketoconazole. 
(d) Certain prescription medications may be allowed on a case-by-case basis at the discretion of the Investigator and 
Sponsor.  
(e) Hormonal contraceptives are not permitted for female participants, as referenced in Table 3. Female partners of 
male participants can use hormonal contraceptives. 
Subjects must be instructed not to take any medications during study participation, including over-the-counter drug 
products, without first consulting with the investigator. 
7.4 
Diet, Fluid, Activity Control  
Subjects will be confined to the clinic for each of the dosing days as well as a period of time 
sufficient to collect additional post-dose PK samples and monitor for safety and tolerability (Day 
-1 through Day 4 for single-dose cohorts and Day-1 through Day 9 for multiple-dose cohorts). 
During confinement, subjects will be provided 3 standard meals and a snack per day, each 
containing approximately 30% fat (relative to the total calories). The meals served on the day of 
dosing should be similar in nutritional content for each subject in the study. The study menu should 
be recorded and submitted to the study file with a copy provided to the sponsor following 
28 days  
prior to  
Inpatient 
Check-in 
14 days 
 prior to 
Inpatient 
Check-in 
7 days 
prior to 
Inpatient 
Check-in 
72 hours  
prior to 
Inpatient 
Check-in  
48 hours  
prior to 
Inpatient 
Check-in 
24 hours  
prior to 
Inpatient 
Check-in 
Nutraceuticals 
(e.g., St. John’s 
wort, ginseng, 
kava kava, 
ginkgo biloba, 
Chinese herbs, 
and melatonin) 
Prescription 
medications 
(d)(including 
hormonal 
contraceptives(e
)) 
OTC 
medications, 
including 
antacids, 
proton-pump 
inhibitors, and 
H2 receptor 
antagonists (a) 
Nicotine-
containing 
products 
Alcohol-
containing 
products 
Products 
containing 
caffeine or 
xanthine (e.g., 
tea or coffee) 
Immunization/
Vaccines (b) 
 
Vitamin 
supplements 
Poppy seeds 
 
 
Known strong 
inhibitors/induc
ers of CYPs 
3A4/5 (c) 
 
Orexin receptor 
antagonists 
including 
suvorexant 
(Belsomra®), 
lemborexant 
(Dayvigo®), 
and related 
compounds 
 
 
 


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treatment. Breakfast will not be provided on dosing days until at least 4 hours after dose 
administration unless otherwise indicated (i.e., Days 2-6 for MAD cohorts). The meal start and 
stop times and percentage of the meal consumed will be recorded in the source, and appropriate 
electronic case report form (eCRF) for all meals served on dosing days.  
If a blood draw or any study procedure coincides with a meal, the blood draw will take precedence, 
followed by the study procedure and then the meal. 
Subjects will remain in bed at a semi-supine position for 4 hours following the dose administration, 
except as necessitated by the occurrence of an AE or study procedures (e.g., obtaining a 12-lead 
ECG). Subjects must refrain from strenuous exercise from 72 hours before Inpatient Check-in and 
until check-out. 
On the dosing days where extensive PK and/or CSF sampling is indicated (i.e., single-dosing Day 
1 and first and last multiple-dose days, e.g., days 1 and 7), CVN766 or placebo suspension will be 
administered with approximately 240 mL of water after a fast of at least 10 hours. Subjects will 
continue to fast for an additional 4 hours after dosing and eat lunch following the 4-hour PK blood 
and CSF collection. Subjects may consume water ad libitum except for 1 hour before and 1 hour 
after drug administration. 
For the food effect cohort (S3), single-dose administration will be administered after ingesting a 
standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect 
bioavailability and fed bioequivalence studies, Dec 2002). Subjects will finish at least 
approximately 85% of their breakfast within 30 minutes and will receive an investigational product 
30 minutes (±5 minutes) after beginning the meal. The S3 (food effect) cohort meals may be 
staggered to ensure dosing occurs 30 minutes after the beginning of the meal. 
Subjects will also fast for at least 10 hours prior to safety laboratory collection times as indicated. 
However, consumption of water as desired is permitted during this time, except for dosing days, 
as indicated above. 
7.5 
Criteria for Discontinuation or Withdrawal of a Subject 
The primary reason for discontinuation or withdrawal of the subject from the study or study 
medication should be recorded in the eCRF using the following categories. For screen failure 
subjects, Section 9.1.15. 
1. The subject has experienced a PTE or AE that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health or the subject is unwilling 
to continue because of the PTE or AE. 
2. Liver Function Test (LFT) Abnormalities 
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests, until a subject’s laboratory profile has returned to 
normal/baseline status) if the following circumstances occur at any time during study 
medication treatment: 
– ALT or AST >8 × ULN, or 
– ALT or AST >5 × ULN and persists for more than 2 weeks, or 


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– ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or INR >1.5, 
or 
– ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). 
3. Significant protocol deviation. The discovery post-randomization that the subject failed to 
meet protocol entry criteria or did not adhere to protocol requirements and continued 
participation poses an unacceptable risk to the subject’s health. 
4. Lost to follow-up. The subject did not return to the clinic, and attempts to contact the subject 
were unsuccessful. Attempts to reach the subject must be documented. 
5. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF. 
Note: All attempts should be made to determine the underlying reason for the withdrawal, and, 
where possible, the primary underlying reason should be recorded (i.e., withdrawal due to an 
AE). 
6. The sponsor, IRB, IEC, or regulatory agency terminates the study. 
7. Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
7.6 
Procedures for Discontinuation or Withdrawal of a Subject 
The investigator must discontinue a subject’s study participation at any time during the study when 
the subject meets the study discontinuation criteria described in Section 7.5. In addition, a subject 
may discontinue his or her participation without giving a reason at any time during the study. 
Should a subject’s involvement be terminated, the primary criterion for termination must be 
recorded by the Investigator. In addition, efforts should be made to perform all procedures 
scheduled for the Early Termination Visit. Discontinued or withdrawn subjects may be replaced 
at the  Sponsor’s discretion. 
Participants who withdraw from the study prior to dosing may be replaced. If a participant 
withdraws after the first dose of study medication or placebo, no replacement will occur. 


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8.0 
CLINICAL TRIAL MANAGEMENT 
8.1 
Study Medication and Materials 
This section contains information regarding all medication and materials provided directly by the 
sponsor and/or sourced by other means required by the study protocol, including important 
sections describing the management of clinical trial material. 
8.1.1 Dosage Form, Manufacturing, Packaging, and Labeling 
Study drug refers to CVN766 and matching placebo. Study drug will be provided in bulk supply. 
An unblinded pharmacist will manage and prepare doses as oral suspensions as needed throughout 
the study.  
In this protocol, the term study medication refers to all or any of the drugs defined below. 
8.1.1.1 Investigational Drug 
CVN766 and Matching Placebo 
CVN766 drug substance is supplied as a bulk powder to the clinical site and then compounded 
into oral suspensions. A matching placebo suspension containing all of the components of the 
active oral suspension with the exception of the drug substance will also be compounded by the 
site. Compounding instructions will be outlined in a separate pharmacy manual and provided by 
the sponsor. See Table 4 for the composition of the drug product and matching placebo 
suspensions.  
The oral suspensions will be labeled with the appropriate study information and caution 
statements.  
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo 
Component 
 
CVN766 Oral Suspension (individual dose) 
Matching 
Placebo 
CVN766 drug substance 
5 mg 
15 mg 
45 mg 
125 mg 
250 mg 
NA 
 Commercial suspending 
vehiclea 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
NA=Not applicable 
a An off-the-shelf commercial suspending vehicle will be used, and the details of the vehicle will be provided in the 
Pharmacy Manual. 
8.1.1.2 Ancillary Materials  
Ancillary materials will be provided by either the clinical site and/or the sponsor based on 
availability.  
Ancillary material details are provided in the pharmacy manual. 


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Table 5 
Planned Single and Multiple Dose Levels by Cohort 
Single-Dose Cohorts 
 
 
 
Cohort 
Planned Treatment* 
No. of Subjects 
Medication Type 
S1  
CVN766 5 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S2 
CVN766 15 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S3 Fasted 
CVN766 45 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S3 Fed (Same 8 subjects as 
in the S3 FASTED cohort) 
CVN766 45 mg 
6 
oral suspension 
 
Placebo 
2 
oral suspension 
S4 
CVN766 125 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
S5 
CVN766 250 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
Multiple Dose Cohorts 
Cohort 
Planned Treatment* 
No. of Subjects 
Medication Type 
M1  
CVN766 45 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
M2  
CVN766 125 mg 
6 
oral suspension 
Placebo 
2 
oral suspension 
M3 
CVN766 250 mg 
6 
oral suspension 
 
Placebo 
2 
oral suspension 
* Dose (active or placebo) is in 10 mL of suspension. 
8.1.4 Overdose 
An overdose is defined as a known, deliberate, or accidental administration of an investigational 
drug, to or by a study subject, at a dose above that assigned to that individual subject according to 
the study protocol. 
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF, in order to capture this important safety information consistently in the database. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE eCRF(s) according to Section 9.7.2, PTEs and AEs. 
Serious adverse events (SAEs) associated with an overdose should be reported according to the 
procedure outlined in Section 9.7.4, Collection and Reporting of SAEs. 
In the event of an overdose, supportive measures should be employed as needed, e.g., 
administration of supportive therapy as dictated by the subject’s clinical status, removal of 
unabsorbed material from the gastrointestinal tract, or the initiation of additional clinical 
monitoring.  


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8.2 
Investigational Drug Assignment and Dispensing Procedures 
Subjects will be assigned to receive a unique randomization number.  
The clinical site will use the unique identifier to facilitate the pre-labeling of PK samples. It should 
also be contained on the PK transport vials shipped to the bioanalytical laboratory and will be used 
by the laboratory to report the subject data results. This unique identifier should only be used for 
the purposes described in this section. This identifier will be assigned upon randomization in the 
order in which subjects receive their first dose of the study drug.   
8.3 
Randomization Code Creation and Storage  
The sponsor or their designee will generate the randomization schedule and provide a copy to the 
site pharmacist and bioanalytical laboratory prior to the start of the study. All randomization 
information will be stored in a secured area, accessible only by authorized personnel.  
8.4 
Investigational Drug Blind Maintenance 
The investigational drug blind is maintained through a randomization schedule held by the 
dispensing pharmacist. 
8.5 
Unblinding Procedure 
The investigational drug blind shall not be broken by the investigative staff unless information 
concerning the investigational drug is necessary for the medical treatment of the subject. All study 
assessments and causality assessments should be performed, if possible, prior to unblinding. In the 
event of a medical emergency, if possible, the medical monitor should be contacted to discuss the 
need for unblinding before the investigational drug blind is broken. 
Unblinding envelopes will be supplied to the site prior to the first subject dosing and stored in a 
central and secure place to ensure access in the event of an emergency.  Study staff will be trained 
on unblinding procedures. 
The sponsor must be notified as soon as possible if the investigational drug blind is broken. The 
date, time, and reason the blind is broken must be recorded in the source documents, and the same 
information (except the time) must be recorded on the eCRF. 
If any site personnel inadvertently become unblinded, the sponsor must be notified, and the SRG 
will determine whether to discontinue dosing or withdraw from the study of all affected subjects. 
No change should be made to any assessment of the subject after unblinding. 
Following assessment of the AE data and pre-defined criteria for study termination, dose escalation 
may be interrupted/stopped and the blind broken for further analysis. Based on a review of 
unblinded data, the sponsor, in consultation with the Investigator, will decide if and how it is 
appropriate for the study to proceed. 
The Randomization schedule for all subjects will be released for analysis after the database for 
these cohorts is locked. The Investigator will be unblinded after database lock for all the cohorts 
if necessary. 


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8.6 
Accountability and Destruction of Sponsor-Supplied Drugs 
Drug supplies will be counted and reconciled at the site before being returned to the sponsor or 
designee or being destroyed.  
The investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to subjects enrolled in the study. To document appropriate 
use of study medication, the investigator must maintain records of all study medication delivery to 
the site, site inventory used by each subject, and return to the sponsor or designee. 
Upon receipt of study medication, the investigator or designee must verify the contents of the 
shipments against the packing list, ensure the quantity is correct, and the medication is received 
within the labeled storage conditions. If quantity and conditions are acceptable, the investigator or 
designee should acknowledge the receipt of the shipment by signing the bottom half of the packing 
list and send via email and per instructions provided on the form. If any discrepancies exist 
between the packing list and the actual product received, the sponsor must be contacted to resolve 
the issue. The packing list should be filed in the investigator’s essential document file. The 
investigator must maintain 100% accountability for all study medication received and dispensed 
during their entire participation in the study. Proper drug accountability includes, but is not limited 
to: 
• Continuously monitoring expiration dates 
• Frequently verifying that actual inventory matches documented inventory 
• Verifying that the log is completed for the drug lot used to prepare each dose 
• Verifying that all containers used are documented accurately on the log 
• Verifying that required fields are completed accurately and legibly 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
The investigator or designee must record the current inventory of all study medication on a 
sponsor-approved drug accountability log. The following information will be recorded at a 
minimum: protocol number and title, name of the Investigator, site identifier and number, 
description of study medication, expiry date, and amount dispensed, including the initials of the 
person dispensing and receiving the study medication. The log should include all required 
information as a separate entry for each subject to whom study medication is dispensed. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform clinical study material accountability and reconciliation before clinical study 
materials are returned to the sponsor or its designee for destruction, or destroyed at the site, as 
applicable. The investigator will retain the original documentation regarding clinical study 
material accountability, return, and/or destruction, and copies will be sent to the sponsor or 
designee. 
The investigator will be notified of any expiry date or retest date extension of clinical study 
material during the study conduct. On expiry date notification from the sponsor or designee, the 
site must complete all instructions outlined in the notification, including segregation of expired 
clinical study material for return to the sponsor or its designee for destruction. 


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9.0 
STUDY PLAN 
9.1 
Study Procedures 
The following sections describe the study procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same investigator or site personnel whenever possible. The 
Schedule of Study Procedures is located in Appendix A. 
9.1.1 Informed Consent Procedure 
The requirements of the ICF are described in Section 14.2. 
The ICF must be obtained prior to the subject entering the study and before any protocol-related 
procedures are performed. 
A unique subject screening number (of the form xx-xxx), the first two numbers for the site, 
subsequent three numbers for subject identification will be assigned to each subject when the ICF 
is obtained. This subject ID will be used until the subject is assigned their 4-digit randomization 
number. 
9.1.1.1 Pharmacogenomic and Cerebrospinal Fluid Informed Consent Procedure 
Pharmacogenomics and cerebrospinal fluid informed consent is a component of the overall study 
ICF. The requirements are described in Section 14.2. 
The pharmacogenomic and (for applicable cohorts) cerebrospinal fluid sample collection is 
mandatory. 
9.1.2 Demographics, Medical History, and Medication History Procedure 
Demographic information to be obtained will include date of birth, sex, ethnicity, race as described 
by the subject, smoking status, and caffeine consumption at Screening. 
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases that stopped at or prior to signing the ICF. Ongoing conditions are 
considered concurrent medical conditions (see Section 9.1.7). 
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days before signing ICF. 
9.1.3 Physical Examination Procedure 
A physical examination performed by the investigator or medical officer consist of the following 
body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; 
(5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; 
(9) nervous system; (10) lymph nodes; and (11) other.  
Any abnormal change from the baseline physical examination (Screening and Inpatient Check-in 
[Day -1]) must be assessed as not CS or CS by the investigator and recorded in the source document 
and eCRF.  


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All CS findings/changes, as determined by the investigator, from the baseline physical 
examination will be recorded as a PTE or concurrent medical condition in the source document 
and on the appropriate eCRF described in Section 9.8.1 or Section 9.8.2.  
On subsequent examinations, any abnormal change from the pretreatment physical examination 
assessment occurring immediately prior to the start of the investigational drug Inpatient Check-in 
(Day -1) must be assessed as not clinically significant (NCS) or CS by the investigator and 
recorded in the source document and eCRF. Any CS change or new diagnosis as a result of a CS 
change, as determined by the investigator, will be recorded as an AE in source documentation and 
on the PTE/AE eCRF. 
9.1.4 Weight, Height, and BMI 
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below:  
Height is recorded centimeters without decimal places, and for weight, it is kilograms (kg) with 1 
decimal place. BMI should be derived as: 
Metric:  
BMI = weight (kg)/[height (m)]2 
Results for BMI will be expressed with 1 decimal place. 
Example: 
Height=176 cm (or 1.76 m), weight=79.2 kg; BMI=79.2/1.762=25.57 kg/m2 captured as 
25.6 kg/m2.  
9.1.5 Vital Sign Procedure 
Vital signs will include tympanic body temperature, respiration, pulse, and blood pressure and be 
collected at timepoints specified in the Schedule of Study Procedures (Appendix A). For eligibility 
determination, the pulse will not be derived from ECG. Pulse and blood pressure will be measured 
after at least 5 minutes supine and again after 2 minutes standing.  
Vital signs should be measured at the same time (+/- 1 hour) of the day across visits if possible. 
When vital signs are scheduled at the same time as blood draws, the blood draw will take priority, 
and vital signs will be obtained within approximately 0.25 hours before or after the scheduled 
blood draw. 
9.1.6 Documentation of Concomitant Medications 
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by the sponsor. At each study visit, subjects will be asked whether they have taken 
any medication other than the study medication (used from the signing of ICF through the end of 
the study), and all medication, including vitamin supplements, over-the-counter medications, and 
oral herbal preparations, must be recorded in the eCRF. Documentation will include generic 
medication name, dose, unit, frequency, route of administration, start and end dates, and reason 
for use. 


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9.1.7 Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at the signing of ICF. This includes CS laboratory, ECG, or physical examination abnormalities 
noted at Screening examination. The condition (i.e., diagnosis) should be described. 
9.1.8 ECG Procedure  
Standard 12-lead ECGs will be recorded at timepoints specified in the Schedule of Study 
Procedures (Appendix A). Triplicate ECGs will be taken at least 1-minute apart at each scheduled 
time. The average of the ECG measurements will be used for determining eligibility. Additional 
unscheduled ECGs may be recorded where clinically necessary for subject safety. 
When an ECG is scheduled at the same time as blood draws or vital signs, then the blood draws 
and vital signs will take priority, and the ECG will be obtained within 0.5 hour before or after the 
scheduled blood draw/vital sign assessment. If an ECG coincides with a meal, ECG will take 
precedence, followed by the meal. 
All stationary 12-lead ECG machines will be supplied by the site. Subjects should be in a supine 
position following an approximate 10-minute rest period for ECG recordings. Should technical 
difficulties occur during the recording of the ECG, a reasonable attempt should be made to repeat 
the ECG shortly after the failed attempt.  
ECGs will be read automatically, and also, the investigator or sub-investigator will manually 
interpret the ECG using 1 of the following categories: within normal limits, abnormal but not CS, 
or abnormal and CS. Abnormal QTc readings will be manually recalculated and reported by the 
Investigator on the eCRF. All 12-lead ECGs will be stored for manual measurement of intervals, 
if necessary. Twelve-lead ECGs will be recorded using an ECG machine that automatically 
calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and 
QTcF and QTcB (Fridericia’s and Bazett’s correction) intervals. Paper ECG traces will be 
recorded for 10 seconds at a standard paper speed of 25 mm/sec, and gain of 10 m/mV or digital 
recordings will be used.  
One copy of the 12-lead ECG with the physician’s signature and date of assessment will be filed 
with the source documents and captured in the appropriate eCRF. If the original ECG is printed 
on thermal paper, the ECG report must be photocopied and certified. The photocopy will be filed 
with the original ECG in the source. 
All ECGs will be recorded at the time points detailed in Appendix A. 
9.1.9 Pharmacogenomic Sample Collection 
Every subject must sign ICF/be consented to the sampling of whole blood for pharmacogenomic 
analysis to participate in the study. 
One whole blood sample for DNA isolation and genotyping will be collected at time points 
specified in the Schedule of Study Procedures (Appendix A) into plastic dipotassium 
ethylenediamine-tetra acetic acid (K2EDTA) spray-coated tubes and stored under frozen 
conditions. In addition, two whole blood samples will be collected at time points specified in the 
Schedule of Study Procedures (Appendix A) for ribonucleic acid (RNA) pharmacogenomic 


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analysis. The pre-dose RNA blood samples should be collected under fasted conditions and prior 
to any other blood collection. 
DNA may be evaluated for the genetic contribution to how the drug is broken down or affects the 
body. This is called a “pharmacogenomics research study.” Specific purposes of this study include: 
• Identifying genetic reasons why certain people respond differently to CVN766 
• Finding out more information about how CVN766 works 
• Generating information needed for research, development, and regulatory approval of tests to 
predict response to CVN766 
• Identifying variations in genes related to the biological target of CVN766 
This information may be used, for example, to develop a better understanding of the safety and 
efficacy of CVN766 and other study medications and for improving the efficiency, design, and 
study methods of future research studies. 
The samples will be stored no longer than 15 years after completion of the CVN766 study and/or 
until the drug development of CVN766 is no longer actively pursued by the sponsor or its 
collaborators. No samples will be stored for longer than permitted by the applicable law, and 
samples will be destroyed upon notification from the sponsor. “Stored samples” in this context are 
defined as samples that are double coded (the samples are stripped of all personal identifying 
information but a key links the samples to the clinical data collected from the sample donor) and 
are used in the analysis of investigational drug or related drug. 
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; every 
subject must sign the ICF in order to participate in this study. DNA samples will be collected and 
may be used to evaluate drug metabolic enzyme and transporter polymorphisms that may 
contribute to the variability in the PK of CVN766. Also, since pharmacogenomics is an evolving 
science, many genes and their functions are not yet fully understood. Future data may suggest a 
role of some of these genes in drug response, which may lead to additional hypothesis-generating 
exploratory research and diagnostic development on stored samples. 
If necessary and feasible, a second aliquot of blood may be taken if isolation of DNA and RNA 
from the first sample was not successful or possible. 
Samples will be frozen at -70°C or lower and shipped separately on dry ice prior to extraction and 
storage at -70°C or lower. Samples should not be allowed to thaw until processed. 
Detailed instructions for the handling and shipping of samples are provided in a separate lab 
manual. 
Genotyping on collected samples may be deferred until after the completion of the study’s in-life 
activities. 
Each pharmacogenomic sample for a study subject should be identifiable on the requisition form 
with the 4-digit randomization number. 


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CVN766 
 
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CONFIDENTIAL 
sampling times, will be used in all computations involving sampling times. The following PK 
parameters will be determined from concentrations of CVN766 in plasma and CSF:  
 
Symbol/Term 
Definition 
Plasma 
AUCt 
Area under the plasma concentration-time curve from the time of dosing to the time of the 
last measurable concentration 
AUC∞  
Area under the plasma concentration-time curve from time 0 to infinity, calculated as 
AUC∞=AUCt+Clast/λz, where Clast is the last quantifiable concentration. 
AUC24 
Area under the plasma concentration-time curve from time 0 to 24 hours, calculated using 
the linear trapezoidal rule. 
AUCτ 
Area under the plasma concentration-time curve over the dosing interval (τ) 
Cmax 
Maximum observed plasma concentration. 
Cmin 
Minimum observed plasma concentration; pre-dose trough concentration 
Minimum observed plasma concentration at steady state, on last day of dosing 
CL/F 
 
Apparent clearance after extravascular administration, calculated as Dose/AUC∞ after a 
single dose. 
CL/Fss 
Apparent clearance after extravascular administration at steady state, calculated as 
Dose/AUCtau 
λz 
Terminal elimination rate constant, calculated as the negative of the slope of the log-linear 
regression of the natural logarithm concentration-time curve during the terminal phase 
t1/2z 
Terminal elimination half-life, calculated as ln(2)/λz. 
tmax 
Time to reach Cmax. 
Vz/F 
 
Apparent volume of distribution during the terminal phase after extravascular 
administration, calculated as (CL/F)/λz. 
Vz/Fss 
Apparent volume of distribution during the terminal phase after extravascular 
administration at a steady-state, calculated as (CL/Fss)/λz 
CSF 
plasma: CSF ratio 
ratio of the drug concentration in plasma vs. CSF 
 
Additional PK parameters may be calculated as appropriate. 
9.1.12 Procedures for Clinical Laboratory Samples 
All samples will be collected in accordance with acceptable laboratory procedures on the 
days/times stipulated in the Schedule of Study Procedures (Appendix A). 
Table 10 lists the tests that will be obtained for each laboratory specimen. 
Table 10 
Clinical Laboratory Tests 
Hematology 
Serum Chemistry 
Urinalysis 
Special 
RBC 
WBC with differential  
     (% and absolute) 
Hemoglobin 
Hematocrit 
ALT 
Albumin 
Alkaline phosphatase 
Lipase (d) 
AST 
pH 
Specific gravity 
Protein 
Glucose 
Blood  
Prolactin 
TSH 
(and if abnormal) 
reflex FT4 


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Platelets 
PT/INR 
Total bilirubin 
Direct bilirubin 
Total protein 
Creatinine 
BUN/Urea 
Creatine kinase 
GGT 
Potassium 
Sodium 
Glucose 
Chloride 
Bicarbonate 
Calcium 
Nitrite 
Microscopic Analysis 
(only if positive dipstick 
results):  
RBC/high power field 
WBC/high power field 
Epithelial cells, casts 
etc. 
Diagnostic Screening: 
Serum 
Urine/ Blood 
Serum hCG (a) 
FSH (b)  
Hepatitis panel, including HBsAg and anti-HCV (e) 
Human Immunodeficiency Virus (HIV) antibody 
Drug screen including amphetamines (AMP), 
barbiturates (BAR), benzodiazepines (BZO), 
cannabinoids, cocaine (COC), opiates (OPI), 
alcohol, cotinine c methamphetamines, 
methadone (MET), 
methylenedioxymethamphetamine (MDMA), 
phencyclidine (PCP), tetrahydrocannabinol 
(THC) 
Urine Pregnancy Test (a) 
Alcohol (can be performed via breath test) 
FT4= free T4, FSH= follicle-stimulating hormone, GGT=γ-glutamyl transferase, hCG= human chorionic 
gonadotropin, PT=prothrombin time, RBC=red blood cells, TSH= thyrotropin, WBC=white blood cells. 
(a) Serum hCG pregnancy test will be done at Screening,  Urine Pregnancy Test will be done at Check-in (Day -1).  
(b) FSH level will be obtained for female subjects at Screening if they are postmenopausal (i.e., last regular 
menstrual cycle >2 years) and not surgically sterile. The result must be >40 IU/L for the subject to be enrolled. 
(c) To be performed at Inpatient Check-in (Day -1). 
(d) To be performed at Day -1 and 24- and 48-hours post-dose. 
(e) Screening Visit only 
The local laboratory will perform all clinical laboratory tests. The results of laboratory tests will 
be returned to the investigator, who is responsible for reviewing and filing these results. All 
laboratory safety data will be transferred electronically to the sponsor or designee in the format 
requested by the sponsor. The investigator will maintain a copy of the laboratory accreditation and 
the reference ranges for the laboratory used.  
Laboratory reports must be signed and dated by the Investigator or sub-investigator, indicating that 
the report has been reviewed and any abnormalities have been assessed for clinical significance. 
Subjects will be referred to their primary care physician for follow-up of any clinically significant 
findings or where the investigator or medically trained sub-investigator deems appropriate. 
All CS laboratory abnormalities must be recorded as a PTE/AE in the subject’s source documents 
and on the appropriate eCRF. A CS laboratory abnormality that has been verified by retesting will 
be followed until the abnormality returns to an acceptable level, or a satisfactory explanation has 
been obtained. 


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If subjects experience ALT or AST >3 ×ULN, follow-up laboratory tests at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR should be performed within a 
maximum of 7 days and preferably within 48 to 72 hours after the abnormality was found. 
(Please refer to Section 7.5 for discontinuation criteria and Section 9.8.3 for the appropriate 
guidance on Reporting of Abnormal LFT in relation to ALT or AST >3 ×ULN in conjunction with 
total bilirubin >2 ×ULN). 
If the ALT or AST remains elevated >3 ×ULN on these 2 consecutive occasions, the investigator 
must contact the Medical Monitor for consideration of additional testing, close monitoring, 
possible discontinuation of study medication, discussion of the relevant subject details and possible 
alternative etiologies. The abnormality should be recorded as an AE (please refer to Section 9.8.3 
Reporting of Abnormal LFT for reporting requirements). 
9.1.13 Contraception and Pregnancy Avoidance Procedure 
From the date of signing of ICF, throughout the duration of the study, and for 30 days after the last 
dose of study medication, females of childbearing potential* must use two acceptable methods of 
contraception and must agree not to donate eggs; Nonsterilized** male subjects who are sexually 
active with a female partner of childbearing potential* must use two acceptable method(s) of 
contraception throughout the duration of the study, and for 90 days after the last dose of study 
medication. In addition, males must be advised not to donate sperm for 90 days after the last dose 
of study medication. 
Females of childbearing potential are defined as any female who has experienced menarche and 
who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not 
postmenopausal.  
Menopause is defined as at least 2 years since last regular menses with an FSH>40 IU/L or at least 
5 years since last regular menses, confirmed before any study medication is implemented. Male 
subjects with potentially postmenopausal partners who are under the age of 55 years must use 
condoms unless their partner’s postmenopausal status has been confirmed by FSH level.  
**Sterilized males should be at least 90 days post-vasectomy and confirm that they have obtained 
documentation of the absence of sperm in the ejaculate. 
Acceptable and highly effective methods of contraception are: 
Note: hormonal contraceptives are not permitted for female participants, as referenced in Table 
3. Female partners of male participants can use hormonal contraceptives.. 
• 
Nonhormonal intrauterine device (IUD) 
• 
Bilateral tubal occlusion 
• 
Vasectomised subject/partner with documented azoospermia 90 days after the 
procedure, if that partner is the sole sexual partner 
• 
Same-sex intercourse, if used consistently for the duration of the study and post-dosing 
as specified above  
Complete abstinence, defined as the complete avoidance of heterosexual intercourse - is an 
acceptable form of contraception if used consistently throughout the study and for the durations 


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after dosing specified for males and females above. It is not necessary to use any other method of 
contraception when complete abstinence is elected. Females of childbearing potential who choose 
complete abstinence must continue to have pregnancy tests as per protocol. The reliability of 
sexual abstinence needs to be evaluated by the Investigator in relation to the duration of the clinical 
trial and the preferred and usual lifestyle of the subject. 
Subjects will be provided with information on acceptable methods of contraception as part of the 
subject's informed consent process and will be asked to sign an ICF stating that they understand 
the requirements for avoidance of pregnancy, egg donation, and sperm donation during the study.  
9.1.14 Pregnancy 
Women who are pregnant or breastfeeding will not be included in this study.  
If any subject is found to be pregnant during the study, she should be withdrawn, and any sponsor-
supplied drug should be immediately discontinued. In addition, any pregnancies in the partner of 
a male subject during the study or for 90 days after the last dose should also be recorded following 
authorization from the subject’s partner.  
If the pregnancy occurs during administration of active study medication, e.g., after Visit 1 or 
within 30 days of the last dose of active study medication, the pregnancy should be reported 
immediately, using a pregnancy notification form, to the contact listed in Section 1.0. 
Should the pregnancy occur during or after administration of the blinded drug, the investigator 
must inform the subject of their right to receive treatment information. If the subject chooses to 
receive unblinded treatment information, the individual blind should be broken by the investigator. 
Subjects randomized to placebo need not be followed. 
If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time she became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable). 
All reported pregnancies will be followed up to the final outcome using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation 
after the birth of the child will also be conducted for 8 weeks. 
9.1.15 Documentation of Screen Failure 
Investigators must account for all subjects who sign ICF. If the subject is not eligible at this visit, 
the investigator should complete the eCRF screen failure form. 
The primary reason for screen failure is recorded in the eCRF using the following categories: 
• PTE/AE 
• Did not meet inclusion criteria or did meet exclusion criteria 
• Significant protocol deviation 
• Lost to follow-up 
• Voluntary withdrawal 


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• Study termination 
• Other 
Subject numbers assigned to subjects who fail screening should not be reused.  
If a subject fails screening, but is later successfully rescreened, the data for the subject will be 
entered as if these were two separate subjects. Therefore, the data should be entered as follows: 
1. The screen failure data should be entered as a screen failure subject. 
2. Rescreened subjects should be assigned a new subject number and treated as a stand-alone 
subject. 
9.1.16 Documentation of Randomization 
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for randomization into the treatment phase. 
If the subject is not eligible for randomization, the investigator should record the primary reason 
for failure on the applicable eCRF. 
9.2 
Monitoring Subject Treatment Compliance 
Study medication will be administered while subjects are under observation in the clinical research 
unit. Following administration of the study medication, appropriate mouth and/or hand checks will 
be performed to ensure that the dose is swallowed and noted in the source document. The date and 
time of each dose will be recorded in the source documents and on the eCRFs. An inventory of the 
study medication supplies dispensed will be performed by the site pharmacist or authorized study 
designee and recorded onto the Drug Accountability Log in the subject’s source document records 
or equivalent. The exact dose time of consecutive subjects may be staggered to facilitate logistics 
at the site. 
9.3 
Schedule of Observations and Procedures 
The study-related procedures schedule for all evaluations is shown in Appendix A and is not 
duplicated in the following sections.  
9.3.1 Screening 
Subjects will be screened within 28 days prior to randomization. Subjects will be screened in 
accordance with predefined inclusion and exclusion criteria as described in Section 7.0. See 
Section 9.1.15 for procedures for documenting screening failures. Subjects who are screening 
failures may be screened a second time if their reason for failing screening is thought to be 
resolved. Rescreened subjects will receive a new Screening number. 
9.3.2 Inpatient Check-In 
All subjects will be admitted to the study clinic the day prior to randomization and first dose.  
Subjects participating in the food effect cohorts will also check into the study clinic the day prior 
to the scheduled dosing. 


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9.3.3 Final Visit (discharge day from clinic) 
Subjects will be confined to the study clinic for the duration of the treatment period to permit 
supervised dosing of study drug and repeat study assessments.  Subjects participating in the single-
dose study and food effect assessment will be discharged no sooner than 72 hours post-dose, and 
subjects participating in the multiple-dose study will be discharged no sooner than 48 hours 
following their last dose.   
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 
9.3.4 Early Termination 
Subjects who discontinue dosing or decide to check out of the study clinic early will be advised to 
allow the Investigator (or authorized designees) to complete early termination assessments for 
safety purposes prior to discharge. The reason for discontinuation must be documented in the 
source document and eCRF.  
For all subjects receiving study medication, the investigator must complete the End of Study eCRF 
page. 
9.3.5 Follow-up Visit  
The Follow-up Visit will occur by telephone approximately 14 days (±2) after the final dose of 
study drug for the SAD cohorts and MAD cohorts unless abnormal CS findings were observed 
upon discharge or the SRG has determined additional PK sampling timepoints are indicated. In 
these cases, subjects must then be brought back to the clinic for re-evaluation per the investigator’s 
discretion.  
9.4 
Biological Sample Retention and Destruction  
In all cohorts except S3 (fed), blood serum will be obtained on Day -1 and Day 2, and the collected 
serum will be stored at -70C to enable additional, retrospective analyses as needed. Samples will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. 
Blood specimens for genome/gene analysis will be collected as described in Section 9.1.9, 
Pharmacogenomic Sample Collection. After extraction and purification, the genetic material will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. Blood and urine samples for PK analysis will be 
collected as described in Section 9.1.10, PK Sample Collection.  Once PK analysis is complete, 
backup plasma and urine samples will be preserved and retained at a biorepository selected by the 
sponsor for up to, but not longer than, 15 years or as required by applicable law, to enable the 
conduct of exploratory, qualitative, metabolite identification studies or measurement of target 
related biomarkers, should the sponsor decide these are informative. The sponsor has put a system 
to protect the subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction. 
The sample will be labeled with a unique sample identifier similar to labeling in the main study 
but using a code different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 


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code numbers; the samples are stripped of all personally identifying information, but a key linking 
the samples to clinical analysis data exists. This link means that the subject may be identified but 
only indirectly. The code numbers will be kept secure by or on behalf of the Sponsor. 
Subjects who consented and provided a pharmacogenomic sample for DNA and RNA analysis can 
withdraw their consent and request disposal of a stored sample at any time prior to analysis. The 
Investigator will notify the sponsor of any subject who has withdrawn consent for the DNA and 
RNA analysis. 
9.5 
Blood Volume 
Direct venipuncture or intravenous cannula is the preferred method of blood collection. Any other 
method will need to be approved by the sponsor. The maximum volume of blood at any single day 
is approximately 111 mL, with the maximum amount not to exceed 500mL for the duration of 
study participation.  
9.6 
CSF Volume 
CSF will be collected by lumbar puncture, performed by a skilled and qualified individual. The 
maximum volume of CSF to be collected will be approximately 10 mL per subject.  
9.7 
Definitions 
9.7.1 PTE 
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed the ICF to participate in a study but prior to administration of any study medication; it does 
not necessarily have to have a causal relationship with study participation. 
9.7.2 AE 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (e.g., a CS abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a drug whether or not it is 
considered related to the drug. 
9.7.3 Additional Points to Consider for PTEs and AEs 
An untoward finding generally may: 
• Indicate a new diagnosis or unexpected worsening of a pre-existing condition. (Intermittent 
events for pre-existing conditions underlying disease should not be considered PTEs or AEs) 
• Necessitate therapeutic intervention 
• Require an invasive diagnostic procedure 
• Require discontinuation or a change in dose of study medication or a concomitant medication 
• Be considered unfavorable by the investigator for any reason 


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• PTEs/AEs caused by a study procedure (e.g., a bruise after blood draw) should be recorded as 
a PTE/AE 
Diagnoses vs. signs and symptoms: 
• Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as a PTE(s) or as an AE(s). 
Laboratory values and ECG findings: 
• Changes in laboratory values or ECG parameters are only considered to be PTEs or AEs if 
they are judged to be CS (i.e., if some action or intervention is required or if the investigator 
judges the change to be beyond the range of normal physiologic fluctuation). A laboratory re-
test and/or continued monitoring of an abnormal value are not considered an intervention. In 
addition, repeated or additional noninvasive testing for verification, evaluation, or monitoring 
of an abnormality is not considered an intervention 
• If abnormal laboratory values or ECG findings are the results of pathology for which there is 
an overall diagnosis (e.g., increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as a PTE or as an AE 
Pre-existing conditions: 
• Pre-existing conditions (present at the time of signing of the ICF) are considered concurrent 
medical conditions and should NOT be recorded as PTEs or AEs. Baseline evaluations (e.g., 
laboratory tests, ECG, X-rays, etc.) should NOT be recorded as PTEs unless related to study 
procedures.  
• If a subject has a pre-existing episodic condition (e.g., asthma, epilepsy), any occurrence of an 
episode should only be captured as a PTE/AE if the episodes become more frequent, serious, 
or severe in nature; that is, investigators should ensure that the AE term recorded captures the 
change in the condition from Baseline (e.g., “worsening of…”) 
• If a subject has a concurrent degenerative condition (e.g., cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater extent 
than that which would be expected. Again, investigators should ensure that the AE term 
recorded captures the change in the condition (e.g., “worsening of…”) 
Worsening of PTEs or AEs: 
• If the subject experiences a worsening or complication of a PTE after starting administration 
of the study medication, the worsening or complication should be recorded appropriately as an 
AE.  
• If the subject experiences a worsening or complication of an AE after any change in study 
medication, the worsening or complication should be recorded as a new AE. Changes in 
severity of AEs /Serious PTEs: 
• If the subject experiences changes in the severity of an AE/serious PTE, the event should be 
captured once with the maximum severity recorded 


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Preplanned surgeries or procedures: 
• Preplanned procedures (surgeries or therapies) that were scheduled prior to signing informed 
consent are not considered PTEs or AEs. However, if a preplanned procedure is performed 
early (e.g., as an emergency) due to a worsening of the pre-existing condition, the worsening 
of the condition should be captured appropriately as a PTE or an AE. Complications resulting 
from any planned surgery should be reported as AEs. 
Elective surgeries or procedures: 
• Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as PTEs or AEs but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs 
Overdose: 
• Cases of overdose with any medication without manifested side effects are NOT considered 
PTEs or AEs, but instead will be documented on an Overdose page of the eCRF. Any 
manifested side effects will be considered PTEs or AEs and will be recorded on the AE page 
of the eCRF 
9.7.4 SAEs 
An SAE is defined as any untoward medical occurrence that at any dose: 
1. Results in DEATH. 
2. Is LIFE-THREATENING 
• The term “life-threatening” refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization 
4. Results in persistent or significant DISABILITY/INCAPACITY 
5. Leads to a CONGENITAL ANOMALY/BIRTH DEFECT 
6. Is an IMPORTANT MEDICAL EVENT that satisfies any of the following: 
• May require intervention to prevent items 1 through 5 above 
• May expose the subject to danger, even though the event is not immediately life-
threatening or fatal or does not result in hospitalization 
• Includes any event or synonym described in the Medically Significant AE List (Table 11)  
PTEs that fulfill 1 or more of the serious criteria above are also considered SAEs and should be 
reported and followed up in the same manner (see Sections 9.8.1 and 9.8.2). 
 


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Table 11 
Medically Significant AE List (categorized as Serious Adverse Events) 
Term 
Acute respiratory failure/acute respiratory distress syndrome 
Hepatic necrosis 
Torsade de pointes / ventricular fibrillation / ventricular 
tachycardia 
Acute liver failure 
Anaphylactic shock 
Malignant hypertension 
Acute renal failure 
Convulsive seizure 
Pulmonary hypertension 
Agranulocytosis 
Pulmonary fibrosis 
Aplastic anemia 
Confirmed or suspected endotoxin shock 
Toxic epidermal necrolysis/Stevens-Johnson syndrome 
Confirmed or suspected transmission of an 
infectious agent by a medicinal product 
 
Neuroleptic malignant syndrome / malignant 
hyperthermia 
 
Spontaneous abortion/stillbirth and fetal death 
 
9.7.5 Severity of PTEs and AEs 
The different categories of intensity (severity) are characterized as follows: 
Mild: 
The event is transient and easily tolerated by the subject. 
Moderate: 
The event causes the subject discomfort and interrupts the subject’s usual activities. 
Severe: 
The event causes considerable interference with the subject’s usual activities. 
9.7.6 Causality of AEs 
The relationship of each AE to study medication(s) will be assessed using the following categories: 
Related: 
An AE that follows a reasonable temporal sequence from the administration of a drug 
(including the course after withdrawal of the drug), or for which possible involvement of the 
drug can be argued, although factors other than the drug, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments, may also be responsible. 
Not Related: 
An AE that does not follow a reasonable temporal sequence from the administration of a drug 
and/or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments. 
9.7.7 Relationship to Study Procedures 
Relationship (causality) to study procedures should be determined for all PTEs and AEs. 
The relationship should be assessed as Related if the investigator considers that there is a 
reasonable possibility that an event is due to a study procedure. Otherwise, the relationship should 
be assessed as Not Related. 
9.7.8 Start Date  
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician. 


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9.7.9 Stop Date  
The stop date of the AE/serious PTE is the date at which the subject recovered, the event resolved 
but with sequelae, or the subject died. 
9.7.10 Frequency  
Episodic AEs/serious PTE (e.g., vomiting) or those which repeatedly occur over a period of 
consecutive days are intermittent. All other events are continuous. 
9.7.11 Action Concerning Study Medication  
• Drug withdrawn – a study medication is stopped due to the particular AE 
• Dose not changed – the particular AE did not require stopping a study medication 
• Unknown – only to be used if it has not been possible to determine what action has been taken 
• Not Applicable – a study medication was stopped for a reason other than the particular AE, 
e.g., the study has been terminated, the subject died, dosing with study medication was already 
stopped before the onset of the AE 
9.7.12 Outcome 
• Recovered/Resolved – Subject returned to first assessment status with respect to the 
AE/serious PTE 
• Recovering/Resolving – the intensity is lowered by one or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved, but has not 
returned to the normal range or to baseline; the subject died from a cause other than the 
particular AE/serious PTE with the condition remaining “recovering/resolving” 
• Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the 
intensity of the diagnosis, signs/ symptoms, or laboratory value on the last day of the observed 
study period had got worse than when it started; is an irreversible congenital anomaly; the 
subject died from another cause with the particular AE/serious PTE state remaining “Not 
recovered/not resolved.” 
• Resolved with sequelae – the subject recovered from an acute AE/serious PTE but was left 
with permanent/significant impairment (e.g., recovered from a cardiovascular accident but 
with some persisting paresis 
• Fatal – the AEs/PTEs which are considered as the cause of death 
• Unknown – the course of the AE/serious PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study 


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9.8 
Procedures 
9.8.1 Collection and Reporting of AEs 
9.8.1.1 PTE and AE Collection Period 
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication Day 1 
or until screen failure. For subjects who discontinue prior to study medication administration, PTEs 
will be collected for the duration of study participation. 
Collection of AEs will commence from the time that the subject is first administered study 
medication Day 1. Routine collection of AEs will continue until 14 days following last dose. 
9.8.1.2 PTE and AE Reporting 
At each study visit, the investigator or designee will assess whether any subjective AEs have 
occurred. A neutral question, such as “How have you been feeling since your last visit?” may be 
asked. Subjects may report AEs occurring at any other time during the study. Subjects 
experiencing a serious PTE must be monitored until the symptoms subside and any clinically 
relevant changes in laboratory values have returned to baseline, or there is a satisfactory 
explanation for the change. Non-serious PTEs, related or unrelated to the study procedure, need 
not be followed up for the purposes of the protocol. 
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or until there is a satisfactory explanation for the 
changes observed. All PTEs and AEs will be documented in the PTE/AE page of the eCRF, 
whether or not the investigator concludes that the event is related to the drug treatment. The 
following information will be documented for each event: 
1. Event term 
2. Start and stop date and time 
3. Frequency 
4. Severity 
5. Investigator’s opinion of the causal relationship between the event and administration of study 
medication(s) (related or not related) (not completed for PTEs) 
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details of 
the suspected procedure 
7. Action concerning study medication (not applicable for PTEs) 
8. Outcome of event 
9. Seriousness 


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9.8.2 Collection and Reporting of SAEs 
When an SAE occurs through the AE collection period, it should be reported according to the 
following procedure: 
An SAE form must be completed in English and signed by the investigator immediately or within 
24 hours of the first onset or notification of the event. The information should be completed as 
fully as possible but contain, at a minimum: 
• A short description of the event and the reason why the event is categorized as serious 
• Subject identification number 
• Investigator’s name 
• Name of the study medication(s) 
• Causality assessment 
The SAE form should be transmitted within 24 hours to the attention of the contact listed in Section 
1.0.  
Any SAE spontaneously reported to the investigator following the AE collection period should be 
reported to the sponsor if considered related to study participation. 
Reporting of Serious PTEs will follow the procedure described for SAEs. 
9.8.3 Reporting of Abnormal LFT 
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an LFT Increases eCRF must be completed 
providing additional information on relevant recent history, risk factors, clinical signs and 
symptoms, and results of any additional diagnostic tests performed. 
If a subject is noted to have ALT or AST >3 ×ULN and total bilirubin >2 ×ULN for which an 
alternative etiology has not been identified, the event should be recorded as an SAE and reported 
as per Section 9.8.2. The investigator must contact the Medical Monitor for discussion of the 
relevant subject details and possible alternative etiologies, such as acute viral hepatitis A or B or 
other acute liver disease or medical history/concurrent medical conditions. Follow-up laboratory 
tests as described in Section 9.1.8 must also be performed. In addition, an LFT Increases eCRF 
must be completed and transmitted with the SAE form (as per Section 9.8.3). 
9.9 
Follow-up of SAEs 
If information is not available at the time of the first report becomes available at a later date, the 
investigator should complete a follow-up SAE form or provide other written documentation and 
fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital notes 
(e.g., ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee if requested. 
All SAEs should be followed up until resuspension or the permanent outcome of the event. The 
timelines and procedures for follow-up reports are the same as those for the initial report. 


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9.9.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory 
Authorities  
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities and IRBs or IECs, as 
applicable, in accordance with national regulations in the countries where the study is conducted. 
Relative to the first awareness of the event by/or further provision to the sponsor or sponsor’s 
designee, SUSARs will be submitted to the regulatory authorities as an expedited report within 7 
days for fatal and life-threatening events and 15 days for other serious events, unless otherwise 
required by national regulations. The sponsor will also prepare an expedited report for other safety 
issues that might materially alter the current benefit-risk assessment of an investigational 
medicinal product or that would be sufficient to consider changes in the investigational medicinal 
products administration or in the overall conduct of the trial. The investigational site also will 
forward a copy of all expedited reports to his or her IRB or IEC in accordance with national 
regulations. 


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10.0 
STUDY-SPECIFIC COMMITTEES 
The Safety Review Group (SRG) will be comprised of the Investigator, Medical Monitor, 
Cerevance Medical Officer and may include other sponsor representatives. A pharmacokineticist 
and other subject matter experts may participate as needed. The responsibilities of the SRG are 
outlined in Section 6.1.3. 


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11.0 
DATA HANDLING AND RECORDKEEPING 
AEs, PTEs, medical history, and concurrent conditions will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization 
(WHO) Drug Dictionary. All terms will be coded using the dictionary version available at the start 
of the study. 
11.1 
CRFs (Electronic) 
Completed eCRFs are required for each subject who signs an informed consent. 
The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRF. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. Data are transcribed directly onto eCRFs. 
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by sponsor 
personnel (or designees) and will be answered by the site.  
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for the change. Reasons for significant corrections should additionally be included.  
The Investigator must review the eCRFs for completeness and accuracy and must sign and date 
the appropriate eCRFs as indicated. Furthermore, the investigator must retain full responsibility 
for the accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The sponsor or its designee will be permitted to review the subject’s medical 
and hospital records pertinent to the study to ensure the accuracy of the eCRFs. The completed 
eCRFs are the sole property of the sponsor and should not be made available in any form to third 
parties, except for authorized representatives of appropriate governmental health or regulatory 
authorities, without the written permission of the sponsor. 
11.2 
Record Retention 
The investigator agrees to keep the records stipulated in Section 11.2 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated ICFs, subject authorization forms regarding the use of 
personal health information (if separate from the ICFs), an electronic copy of eCRFs, including 
the audit trail, and detailed records of drug disposition to enable evaluations or audits from 
regulatory authorities, the sponsor or its designees. Any source documentation printed on 
degradable thermal sensitive paper should be photocopied by the site and filed with the original in 
the subject’s chart to ensure long-term legibility. Furthermore, ICH E6 Section 4.9.5 requires the 
investigator to retain essential documents specified in ICH E6 (Section 8) until at least 2 years 
after the last approval of a marketing application for a specified drug indication being investigated 
or, if an application is not approved, until at least 2 years after the investigation is discontinued 
and regulatory authorities are notified. In addition, ICH E6 Section 4.9.5 states that the study 


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records should be retained until an amount of time specified by applicable regulatory requirements 
or for a time specified in the Clinical Study Site Agreement between the investigator and sponsor. 
Refer to the Phase 1 Site Specifications document for the sponsor’s requirements on record 
retention. The investigator should contact and receive written approval from the sponsor before 
disposing of any such documents. 


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12.0 
STATISTICAL METHODS 
12.1 
Statistical and Analytical Plans 
A statistical analysis plan (SAP) will be prepared and finalized prior to unblinding of the subject’s 
treatment assignment. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all study objectives. 
A targeted data review will be conducted prior to unblinding of the subject’s treatment assignment. 
This review will assess the accuracy and completeness of the study database, subject evaluability, 
and appropriateness of the planned statistical methods. 
12.1.1 Analysis Sets 
Safety Set 
The Safety Analysis Set will consist of all subjects who are enrolled and receive study drug. 
Subjects in this analysis set will be used for demographic, baseline characteristics, and safety 
summaries. 
PK Set 
The PK set will consist of all subjects who receive study drug and have at least 1 measurable 
plasma concentration. 
If any subjects are found to be non-compliant in dosing schedule or with incomplete data, a 
decision will be made on a case-by-case basis as to their inclusion in the analysis but will be 
presented in the subject listings. 
12.1.2 Analysis of Demographics and Other Baseline Characteristics 
Descriptive statistics (N, mean, SD, median, minimum, and maximum) will be generated for 
continuous demographic variables and baseline characteristics variables (age, height, weight, and 
BMI) for pooled placebo, CVN766 dose level, CVN766 overall, and overall. The number and 
percentage of subjects in each class of the categorical demographic variables and baseline 
characteristics variables (gender, ethnicity, and race) will be tabulated for pooled placebo, each 
CVN766 dose level, CVN766 overall, and overall. Individual subject demographic and baseline 
characteristics data will be listed. 
Demographic variables of screen failure subjects and reasons for screen failures will be 
summarized overall for subjects who are screened but not enrolled in the study. Individual 
demographic characteristics, date of informed consent, and reason for screen failure will be listed. 
12.1.3 PK Analysis 
The concentration of CVN766 in plasma and CSF will be summarized by dose over each scheduled 
sampling time using descriptive statistics. Individual concentration data versus time will be 
presented in a data listing. Individual and mean plasma and CSF concentration data will be 
presented graphically.  Descriptive statistics (arithmetic mean, SD, median, minimum and 
maximum) will be used to summarize the plasma and CSF PK parameters for CVN766. In 
addition, geometric mean and coefficient of variation will be computed 
The effect of fed/fasting state on PK and bioavailability of CVN766 will be characterized. 


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Plots of Cmax and AUCs, as well as dose-normalized Cmax and AUCs, versus doses, will be 
generated. 
Dose proportionality will be tested for CVN766 Cmax and AUCs using a power model.  
A more detailed analysis will be presented in the SAP. 
12.1.4 Safety Analysis 
12.1.4.1 AEs 
All AEs will be coded by system organ class (SOC) and preferred term (PT) using MedDRA. 
Treatment-emergent AEs with onset occurring within 30 days (onset date – last date of dose +1 
≤30) after study drug administration will be listed and included in the summary tables. Treatment-
emergent AEs will be summarized by pooled placebo, each CVN766 dose level and CVN766 
overall by SOC and PT. The following summary tables will be included in the report: summary of 
TEAEs and drug-related AEs, relationship of AEs to study drug (related vs. not-related), severity 
of AEs, and related AEs. AEs leading to study drug discontinuation and SAEs will be listed. Data 
listings will be provided for all AEs, including PTE, TEAEs, AEs leading to study drug 
discontinuation, and SAEs. All AEs will be listed. 
12.1.4.2 Clinical Laboratory Evaluation 
Individual results of laboratory tests from hematology, chemistry, and urinalysis that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and change from baseline to post-dose 
laboratory data will be summarized for pooled placebo, each CVN766 dose level, and CVN766 
overall. All clinical laboratory data will be listed. 
12.1.4.3 Vital Signs 
Individual results of vital signs that are abnormal and CS will be summarized and listed. Baseline, 
post-dose, and changes from Baseline in vital sign measurements will be summarized by pooled 
placebo, each CVN766 dose level, and CVN766 overall. All vital sign data will be provided in the 
data listings. 
12.1.4.4 ECGs 
Individual results of quantitative ECG parameters from the 12-lead safety ECGs that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and changes from baseline in 
quantitative ECG parameters will be summarized by pooled placebo, each CVN766 dose level, 
and CVN766 overall. Shift tables may be generated for the investigator’s ECG interpretations that 
changed from baseline to the post-dose collections by the above groups. All ECG data will be 
provided in the data listings. 
12.1.4.5 Other Variables 
Physical exam findings and suicidal assessments will be presented in data listings. 
12.2 
Interim Analysis and Criteria for Early Termination 
No interim analysis is planned. 


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12.3 
Determination of Sample Size 
The sample size chosen of 8 subjects per cohort (6 active: 2 placebo) is considered to be sufficient 
for the evaluation of the safety, tolerability, and PK of each cohort. The sample size was not based 
on statistical power considerations.  


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13.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Study-Site Monitoring Visits 
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution guarantee access to source documents by the sponsor or its 
designee (contract research organization) and by the IRB or IEC. 
All aspects of the study and its documentation will be subject to review by the sponsor or designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, 
study medication, subject medical records, informed consent documentation, documentation of 
subject authorization to use personal health information (if separate from the ICFs), and review of 
eCRFs and associated source documents. It is important that the investigator and other study 
personnel are available during the monitoring visits and that sufficient time is devoted to the 
process. 
13.2 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study subjects. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
designee (and IRB or IEC, as required) to determine the appropriate course of action. There will 
be no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria. 
The site should document all protocol deviations in the subject’s source documents. In the event 
of a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessment. A Protocol Deviation Form should be completed by the site and signed by the sponsor 
or designee for any significant deviation from the protocol. 
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. Table 12 
defines the windows allowed for sample collections.  
Protocol Deviation Forms are to be completed for PK samples collected outside of the following 
intervals: 
Table 12 
Windows for PK Blood Sample Collection 
Minutes 
Nominal Sampling Time 
no more than 15 minutes pre-dose 
0 hour 
±5 
immediately post-dose to ≤6 hours 
±10 
>6 hours to ≤12 hours post-dose 
±15 
>12 hours to ≤24 hours 
±30 
>24 hours 
 


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13.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing 
visit. The auditor may ask to visit the facilities where laboratory samples are collected, where the 
medication is stored and prepared and any other facility used during the study. In addition, there 
is the possibility that this study may be inspected by regulatory agencies, including those of 
Australia (i.e., Therapeutic Goods Administration [TGA]) and foreign governments (e.g., the 
FDA, the United Kingdom Medicines and Healthcare products Regulatory Agency, the 
Pharmaceuticals and Medical Devices Agency of Japan). If the study site is contacted for an 
inspection by a regulatory body, the sponsor should be notified immediately. The investigator and 
institution guarantee access for quality assurance auditors to all study documents as described in 
Section 13.1. 


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14.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual subjects (i.e., subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, 
and the ICH Harmonised Tripartite Guideline for GCP. Each investigator will conduct the study 
according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the “Responsibilities of the Investigator” that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities. 
14.1 
IRB and/or IEC Approval 
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. Those Americas sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services. 
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the ICFs, and, if applicable, subject recruitment materials and/or advertisements and other 
documents required by all applicable laws and regulations must be submitted to a central or local 
IRB or IEC for approval. The IRB’s or IEC’s written approval of the protocol and subject informed 
consent must be obtained and submitted to the sponsor or designee before the commencement of 
the study (i.e., before shipment of the sponsor-supplied drug or study-specific screening activity). 
The IRB or IEC approval must refer to the study by exact protocol title, number, and version date; 
identify versions of other documents (e.g., ICF) reviewed; and state the approval date. The sponsor 
will ship drug/notify site once the sponsor has confirmed the adequacy of site regulatory 
documentation and, when applicable, the sponsor has received permission from a competent 
authority to begin the trial. Until the site receives drug/notification, no protocol activities, 
including screening, may occur. 
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by subjects, local safety reporting requirements, reports, and 
updates regarding the ongoing review of the study at intervals specified by the respective IRB or 
IEC, and submission of the investigator’s final status report to IRB or IEC. All IRB and IEC 
approvals and relevant documentation for these items must be provided to the sponsor or its 
designee. 
Subject incentives should not exert undue influence on participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor. 


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14.2 
Subject Information, Informed Consent, and Subject Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
applicable laws and regulations. The ICF, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and disclosures 
of the subject’s personal and personal health information for purposes of conducting the study. 
The ICF and the subject information sheet (if applicable) further explain the nature of the study, 
its objectives, and potential risks and benefits, as well as the date informed consent is given. The 
ICF will detail the requirements of the subject and the fact that he or she is free to withdraw at any 
time without providing a reason and without prejudice to their other medical care. 
The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and if applicable, the subject authorization form. The ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) must be approved by both the IRB or IEC 
and the sponsor prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject. It is the 
responsibility of the investigator to explain the detailed elements of the ICF, subject authorization 
form (if applicable), and subject information sheet (if applicable) to the subject. Information should 
be given in both oral and written form whenever possible and in the manner deemed appropriate 
by the IRB or IEC. In the event the subject is not capable of rendering adequate written informed 
consent, then the subject’s legally acceptable representative may provide such consent for the 
subject in accordance with applicable laws and regulations. 
The subject, or the subject’s legally acceptable representative, must be given ample opportunity 
to: (1) inquire about details of the study and (2) decide whether or not to participate in the study. 
If the subject, or the subject’s legally acceptable representative, determines they will participate in 
the study, then the ICF and subject authorization form (if applicable) must be signed and dated by 
the subject, or the subject’s legally acceptable representative, at the time of consent and prior to 
the subject entering into the study. The subject or the subject’s legally acceptable representative 
should be instructed to sign using their legal names, not nicknames, using blue or black ballpoint 
ink. The investigator must also sign and date the ICF and subject authorization (if applicable) at 
the time of consent and prior to the subject entering into the study; however, the sponsor may allow 
a designee of the investigator to sign to the extent permitted by applicable law. 
Once signed, the original ICF, subject authorization form (if applicable), and subject information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document 
the date the subject signs the informed consent in the subject’s medical record. Copies of the signed 
ICF, the signed subject authorization form (if applicable), and the subject information sheet (if 
applicable) shall be given to the subject. 
All revised ICFs must be reviewed and signed by relevant subjects or the relevant subject’s legally 
acceptable representative in the same manner as the original informed consent. The date the revised 
consent was obtained should be recorded in the subject’s medical record, and the subject should 
receive a copy of the revised ICF. 


CVN766 
 
Study No. CVN766-101 
Page 67 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
Subjects who consented and provided a pharmacogenomic sample for DNA analysis can withdraw 
their consent and request disposal of a stored sample at any time prior to analysis. Notify sponsor 
of consent withdrawal. 
14.3 
Subject Confidentiality 
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the sponsor’s clinical study database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or 
date of birth, and subject initials may be used to verify the subject and the accuracy of the subject’s 
unique identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (e.g., FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals, and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s study participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process (see Section 14.2). 
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (i.e., subject name, address, and other identifier fields 
not collected on the subject’s eCRF). 
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy 
14.4.1 Publication and Disclosure 
The investigator is obliged to provide the sponsor with complete test results and all data derived 
by the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and/or advertisements, is the sole responsibility of the sponsor. 
The sponsor may publish any data and information from the study, including data and information 
generated by the investigator, without the consent of the investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and review 
of the document. All publications and presentations must be prepared in accordance with this 
section and the Clinical Study Site Agreement. In the event of any discrepancy between the 
protocol and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail. 
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. 


CVN766 
 
Study No. CVN766-101 
Page 68 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
14.4.2 Clinical Trial Registration  
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations, and guidance, the sponsor will register this clinical trial 
on ClinicalTrials.gov (and possibly on other publicly accessible websites) before the start of study.  
Sponsor contact information, along with the investigator’s city, state, country, and recruiting 
status, will be registered and available for public viewing. Once subjects receive investigator 
contact information, they may call the site and request enrollment into the trial. The investigative 
site(s) are encouraged to handle such trial inquiries according to their established subject screening 
process. If the caller asks additional questions beyond the topic of trial enrollment, they should be 
referred to the sponsor.  
14.4.3 Clinical Trial Results Disclosure  
If required at the conclusion of the study, the sponsor will post the results on ClinicalTrials.gov or 
other publicly accessible websites, as required by applicable national and local laws and/or 
regulations. 
14.5 
Insurance and Compensation for Injury 
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject compensation 
and treatment for injury. If the investigator has questions regarding this policy, they should contact 
the sponsor or sponsor’s designee. 


CVN766 
 
Study No. CVN766-101 
Page 69 of 78
Clinical Protocol – Version 3.0 
26 November 2021
 
CONFIDENTIAL 
15.0 
REFERENCES 
FDA Guidance for Industry: Food-effect bioavailability and fed bioequivalence studies (Dec 
2002). 
FDA Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials 
for Therapeutics in Adult Healthy Volunteers. US Dept of Health and Human Services, Food 
and Drug Administration, Center for Drug Evaluation and Research. 06 July 2005. Publication 
No. 5541. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. First-in-human study with ACT-
539313, a novel selective orexin-1 receptor antagonist. Br J Clin Pharmacol. 2020 
Jul;86(7):1377-1386. doi: 10.1111/bcp.14251. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. Multiple-dose clinical pharmacology 
of the selective orexin-1 receptor antagonist ACT-539313. Prog Neuropsychopharmacol Biol 
Psychiatry. 2021 Jun 8;108:110166. doi: 10.1016/j.pnpbp.2020.110166.  
Salvadore G, Bonaventure P, Shekhar A, Johnson PL, Lord B, Shireman BT, Lebold TP, 
Nepomuceno D, Dugovic C, Brooks S, Zuiker R, Bleys C, Tatikola K, Remmerie B, Jacobs 
GE, Schruers K, Moyer J, Nash A, Van Nueten LGM, Drevets WC. Translational evaluation 
of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for 
panic in rodents and humans. Transl Psychiatry. 2020 Sep 7;10(1):308. doi: 10.1038/s41398-
020-00937-9. 
 


CVN766 
 
Study No. CVN766-101 
Page 70 of 78
Clinical Protocol  - Version 3.0 
26 November  2021
 
CONFIDENTIAL 
Appendix A: Schedule of Study Procedures 
SAD Cohorts 1, 2, 4, 5 
 
Screening 
Check-in 
Dosing & Observation 
Discharge 
(a) 
 
Outpatient 
Visit 
Early 
Termination  Follow-up  
Study Day:  
-28 to -2  
Day -1  
Day 1 
Day 2 
Day 3 
Day 4 
Day 8 
Day 14 (±2) 
(b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Demographics and medical 
history 
X 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 
Neurological Exam (o) 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination  
X 
X 
 
 
 
X  
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight, height, and BMI (d) 
X 
X 
 
 
 
X 
X 
X 
 
Urine drug screen 
X 
X 
 
 
 
 
 
 
 
Cotinine screen 
 
X 
 
 
 
 
 
 
 
Concomitant medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical conditions 
X 
X 
 
 
 
 
 
 
 
Clinical laboratory tests (f) 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hepatitis panel and HIV 
antibody test 
X 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
Serum Pregnancy test (hCG)  
X 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
 
X 
 
 
 
 
 
 
 
CV Telemetry (n) 
 
 
X 
X 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
X 
 
PGx DNA sample collection 
(i) 
 
 
X 
 
 
 
 
 
 
PGx RNA collection (j) 
 
 
X 
 
 
 
 
 
 


CVN766 
 
Study No. CVN766-101 
Page 71 of 78
Clinical Protocol – Version 3.0 
 26 November 2021
 
CONFIDENTIAL 
PGx=pharmacogenomic.(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not 
necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these 
cases, subjects must then be brought back to the clinic for re-evaluation per the investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), 
Day 1 (pre-dose [within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 
72 hours post-dose, and at Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the Follow-up Visit Day 14 
(±2 days). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, 
Days 2 through 4, Day 8, Early Termination (if applicable), and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours 
and 48 hours post-dose. An additional tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -
70C to enable additional, retrospective analyses asneeded. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours 
post-dose), and then every 12 hours until 48 hours post-dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) Whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will 
also be collected during the food effect period. 
(k) Blood samples for PK analyses will be collected at time points indicated in Table 6. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
(o) Neurological exam to consist of light touch, power in limbs, and brief cranial nerve examination. 
 
 
 
PK blood collection (k) 
 
 
X 
X 
X 
X 
 
X 
 
Standardized pre-dose meal 
(S3 fed cohorts only) 
 
 
X 
 
 
 
 
 
 
Study drug dosing 
 
 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 


CVN766 
 
Study No. CVN766-101 
Page 72 of 78
Clinical Protocol – Version 3.0 
 26 November 2021
 
CONFIDENTIAL 
Cohort 3 SAD 
 Fasted-Fed Crossover 
 
Screening 
Dosing and Observation  
Inpatient 
D/C 
 
Inpatient 
No sooner than +14 days or 4 half-
lives of Day 8 visit 
 
 
+4 
days 
post 
D/C 
E/T 
F/U 
Study Day: 
Days 
-28 to -2 
Day -1 Day 1 Day 2 Day 3 Day 4 
 
 
Day 8 Day -1 Day 1 Day 2 Day 3 Day 4 
Day 14 
(±2) 
(b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admitted to the Clinic 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Neurological Exam (o) 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
Physical examination  
X 
X 
 
 
 
X  
X 
X 
 
 
 
X  
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight, height, and BMI (d) 
X 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
 
Urine drug screen 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Cotinine screen 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical conditions 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Clinical laboratory tests (f) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Hepatitis panel and HIV antibody 
test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy test (hCG)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy test 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
CV Telemetry (n) 
 
 
X 
X 
 
 
 
X 
X 
X 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
PGx DNA sample collection (i) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PGx RNA collection (j) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PK blood collection (k) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 


CVN766 
 
Study No. CVN766-101 
Page 73 of 78
Clinical Protocol – Version 3.0 
 26 November 2021
 
CONFIDENTIAL 
*S3 Cohort will return no sooner than Day 14 or 4 half-lives (whichever is greater) after Day 8 for the Fed portion. The Fed portion will commence on Day -1 
will all the same schedule of events with the exception of dosing will be post-meal.  
PGx=pharmacogenomic. 
(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must 
then be brought back to the clinic for re-evaluation per the investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose 
[within 1 hour and 30 minutes prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at 
Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood 
pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, 
Day 8, Early Termination (if applicable), and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional 
tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected serum will be stored at -70C to enable additional, retrospective analyses as 
needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and 
then every 12 hours until 48 hours post-dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) Whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be collected 
during the food effect period. 
(k) Blood samples for PK analyses will be collected at time points indicated in Table 6. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
(o) Neurological exam to consist of light touch, power in limbs, and brief cranial nerve examination. 
 
 
Lumbar puncture & CSF collection 
(k) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Standardized pre-dose meal  
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Study drug dosing 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
PTE assessment (l) 
X 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
AE assessment (m) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Discharged from Clinic 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 


CVN766 
 
Study No. CVN766-101 
Page 74 of 78
Clinical Protocol  - Version 3.0 
26 November  2021
 
CONFIDENTIAL 
Multiple-Dose 
Regimen Cohorts 
SCR 
 
Check-
in 
 
Inpatient 
Dosing & Observation 
 
Inpatient 
Discharge 
(a) 
 
Outpatient Visit 
E/T Follow-up 
 
Study Day:  
Days 
-28 to -2  Day -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day  
5 
 (model for 
additional 
dosing 
days) 
Day 6 
Day of last 
dose 
 (e.g. Day7) 
1 day after 
last dose 
(e.g. Day 8) 
2 days after 
last dose 
(e.g. 
Day 9) 
3 days ±0 
after last 
dose (e.g.  
Day 10) 
(o) 
7 days ±1 
after last 
dose (e.g.  
Day 14) 
 
14 days ±2 
after last 
dose (e.g. 
Day 21 ±2) 
(b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neurological exam (p) 
 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Physical examination  
X 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Weight, height, and 
BMI (d) 
X 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Urine drug screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cotinine screen 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent medical 
conditions 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory tests 
(f) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Hepatitis panel and HIV 
antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (g) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy test 
(hCG)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG (h) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
 


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Study No. CVN766-101 
Page 77 of 78
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CONFIDENTIAL 
Appendix B Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations.  
The Investigator agrees to assume the following responsibilities. 
1. Conduct the study in accordance with the protocol. 
2. Personally conduct or supervise the staff who will assist in the protocol. 
3. Ensure that study-related procedures, including study-specific (non-routine/nonstandard 
panel) screening assessments, are NOT performed on potential subjects prior to the receipt of 
written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed 
of these obligations. 
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conforms 
to local regulatory requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity and 
all anticipated risks to subjects. Make at least yearly reports on the progress of the study to 
the IRB/IEC and issue a final report within 3 months of study completion. 
7. Ensure that requirements for informed consent, as outlined in local regulations, are met. 
8. Obtain valid ICF from each subject who participates in the study and document the date of 
consent in the subject’s medical chart. Valid informed consent is the most current version 
approved by the IRB/IEC. Each ICF should contain a subject authorization section that 
describes the uses and disclosures of a subject’s personal information (including personal 
health information) that will take place in connection with the study. If an ICF does not 
include such a subject authorization, then the Investigator must obtain a separate subject 
authorization form from each subject or the subject’s legally acceptable representative. 
9. Prepare and maintain adequate case histories of all persons entering into the study, including 
eCRFs, hospital records, laboratory results, etc., and maintain these data for a minimum of 
2 years following notification by the sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The Investigator should 
contact and receive written approval from the sponsor before disposing of any such 
documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor.  
12. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours. 


CVN766 
 
Study No. CVN766-101 
Page 78 of 78
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CONFIDENTIAL 
Appendix C Investigator Consent to Use of Personal Information  
Cerevance will collect and retain personal information of the Investigator, including their name, 
address, and other personally identifiable information. In addition, Investigator’s personal 
information may be transferred to other parties located in countries throughout the world (e.g., 
the United Kingdom, United States, and Japan), including the following: 
• Cerevance, its affiliates, and licensing partners 
• Business partners assisting Cerevance, its affiliates, and licensing partners 
• Regulatory agencies and other health authorities 
• IRBs and IECs 
• Investigator’s personal information may be retained, processed, and transferred by Cerevance 
and these other parties for research purposes, including the following: 
• Assessment of the suitability of Investigator for the study and/or other clinical studies 
• Management, monitoring, inspection, and audit of the study 
• Analysis, review, and verification of the study results 
• Safety reporting and pharmacovigilance relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study 
• Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may 
contain the same chemical compound present in the study medication 
• Inspections and investigations by regulatory authorities relating to the study 
• Self-inspection and internal audit within Cerevance, its affiliates, and licensing partners 
• Archiving and audit of study records 
• Posting Investigator site contact information, study details, and results on publicly accessible 
clinical trial registries, databases, and websites 
• Investigator’s personal information may be transferred to other countries that do not have 
data protection laws that offer the same level of protection as data protection laws in the 
Investigator’s own country. 
• Investigator acknowledges and consents to the use of their personal information by 
Cerevance and other parties for the purposes described above. 
 


CVN766
Study No. CVN766-101
Page 1 of 76
Clinical Protocol  - Version 4.0
01 June 2022
CONFIDENTIAL 
PROTOCOL 
 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, 
Tolerability, and Pharmacokinetic Study of Escalating Single and 
Multiple Doses of CVN766  
in Healthy Subjects  
Short Title: Phase 1 SAD/MAD Study of CVN766 
 
Sponsor: 
Cerevance Gamma, Inc. 
One Marina Park Drive, Suite 1410 
Boston, MA 02210 
 
Study Number:
CVN766-101
IND Number:
Not Applicable
EudraCT Number: 
Not Applicable
Compound: 
CVN766 
Protocol Version:  
4.0, Amendment 3
Date: 
 01 June 2022
CONFIDENTIAL PROPERTY OF CEREVANCE 
This document is a confidential communication of Cerevance Gamma, Inc. (“Cerevance”). Acceptance of this 
document constitutes the agreement by the recipient that no information contained herein will be published or 
disclosed without written authorization from Cerevance except to the extent necessary to obtain informed consent 
from those persons to whom the drug may be administered. Furthermore, the information is only meant for review 
and compliance by the recipient, their staff, and relevant institutional review committee and regulatory agencies to 
enable the conduct of the study. 


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1.0
ADMINISTRATIVE INFORMATION
1.1
Contacts  
A separate contact information list will be provided for each site.  
 
Contact Type / Role 
Contact 
Serious adverse event and pregnancy reporting
 
Novotech
Medical Monitor  
(carries overall responsibility for the conduct of the study) 
, MD 
Responsible Medical Officer 
(medical advice on protocol and compound)
, MD 
PPD
PPD


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1.2
Approval 
REPRESENTATIVES OF CEREVANCE
This study will be conducted with the highest respect for the individual participants in 
accordance with the requirements of this clinical study protocol and also in accordance with the 
following: 
The ethical principles that have their origin in the Declaration of Helsinki
International Council on Harmonisation (ICH) E6 Good Clinical Practice (GCP)
Consolidated Guideline
All applicable laws and regulations, including, without limitation, data privacy laws, clinical 
trial disclosure laws, and regulations
SIGNATURES 
Approved by:
Signature __
__      
Date__________________________
, M.D.
Medical Monitor
01-JUN-2022
PPD
PPD


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INVESTIGATOR AGREEMENT 
I confirm that I have read and understand this protocol, the Investigator’s Brochure, and any other 
product information provided by the sponsor. I agree to conduct this study in accordance with the 
requirements of this protocol and also to protect the rights, safety, privacy, and well-being of study 
subjects in accordance with the following: 
 The ethical principles that have their origin in the Declaration of Helsinki 
 International Council on Harmonisation, E6 GCP: Consolidated Guideline 
 All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations
 Regulatory requirements for reporting serious adverse events (SAEs) are defined in Section  
9.9 of this protocol 
 Terms outlined in the Clinical Study Site Agreement 
 Appendix B – Responsibilities of the Investigator 
 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix C of this protocol. 
Signature of Investigator 
Date
 
Investigator Name (print or type) 
Investigator’s Title 
Location of Facility (City, State/Provence) 
Location of Facility (Country) 


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CONFIDENTIAL 
TABLE OF CONTENTS
1.0 
ADMINISTRATIVE INFORMATION...........................................................................2
1.1 
Contacts.....................................................................................................................2
1.2
Approval....................................................................................................................3
2.0
STUDY SUMMARY ......................................................................................................9
3.0 
STUDY REFERENCE INFORMATION ...................................................................... 15
3.1 
List of Abbreviations ...............................................................................................15
4.0 
INTRODUCTION ......................................................................................................... 17
4.1
Background .............................................................................................................17
4.2
Rationale for the Proposed Study.............................................................................17
5.0 
STUDY OBJECTIVES AND ENDPOINTS..................................................................18
5.1 
Objectives................................................................................................................ 18
5.1.1
Primary Objective..............................................................................................18
5.1.2
Secondary Objectives.........................................................................................18
5.2 
Endpoints................................................................................................................. 18
5.2.1
Primary Endpoints ............................................................................................. 18
5.2.2
Secondary Endpoints..........................................................................................18
5.2.3
Additional Endpoints .........................................................................................19
6.0 
STUDY DESIGN AND DESCRIPTION.......................................................................19
6.1 
Study Design ........................................................................................................... 19
6.1.1
Part 1: Single-Dose Regimen and Fasted-Fed Crossover .................................... 20
6.1.2
Part 2: Multiple-Dose Regimen .......................................................................... 21
6.1.3
Dose Escalation.................................................................................................. 22
6.2 
Justification for Study Design, Dose, and Endpoints ................................................ 23
6.3
Premature Termination or Suspension of Study or Investigational Site.....................24
6.3.1
Criteria for Premature Termination or Suspension of the Study..........................24
6.3.2
Criteria for Premature Termination or Suspension of Investigational Sites .........25
6.3.3
Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s)................................................................25
7.0 
SUBJECT POPULATION.............................................................................................25
7.1 
Inclusion Criteria ..................................................................................................... 25
7.2 
Exclusion Criteria.................................................................................................... 26
7.3 
Excluded Medications and Dietary Products ............................................................ 28
7.4 
Diet, Fluid, Activity Control ....................................................................................29
7.5 
Criteria for Discontinuation or Withdrawal of a Subject ........................................... 30
7.6 
Procedures for Discontinuation or Withdrawal of a Subject...................................... 31
8.0 
CLINICAL TRIAL MANAGEMENT ........................................................................... 31
PPD


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CONFIDENTIAL 
8.1
Study Medication and Materials...............................................................................31
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling ..................................... 31
8.1.2
Drug Storage...................................................................................................... 32
8.1.3
Dose and Regimen ............................................................................................. 33
8.1.4
Overdose............................................................................................................34
8.2
Investigational Drug Assignment and Dispensing Procedures ..................................34
8.3 
Randomization Code Creation and Storage ..............................................................34
8.4 
Investigational Drug Blind Maintenance .................................................................. 35
8.5 
Unblinding Procedure .............................................................................................. 35
8.6
Accountability and Destruction of Sponsor-Supplied Drugs.....................................35
9.0
STUDY PLAN..............................................................................................................37
9.1 
Study Procedures ..................................................................................................... 37
9.1.1
Informed Consent Procedure..............................................................................37
9.1.2
Demographics, Medical History, and Medication History Procedure .................. 37
9.1.3
Physical Examination Procedure ........................................................................38
9.1.4
Weight, Height, and BMI...................................................................................38
9.1.5
Vital Sign Procedure ..........................................................................................39
9.1.6
Documentation of Concomitant Medications......................................................39
9.1.7
Documentation of Concurrent Medical Conditions ............................................. 39
9.1.8
ECG Procedure.................................................................................................. 39
9.1.9
Pharmacogenomic Sample Collection ................................................................40
9.1.10 PK Sample Collection........................................................................................ 41
9.1.11 PK Parameters ................................................................................................... 43
9.1.12 Procedures for Clinical Laboratory Samples.......................................................44
9.1.13 Contraception and Pregnancy Avoidance Procedure...........................................46
9.1.14 Pregnancy ..........................................................................................................47
9.1.15 Documentation of Screen Failure .......................................................................48
9.1.16 Documentation of Randomization...................................................................... 48
9.2 
Monitoring Subject Treatment Compliance..............................................................49
9.3 
Schedule of Observations and Procedures ................................................................ 49
9.3.1
Screening........................................................................................................... 49
9.3.2
Inpatient Check-In .............................................................................................49
9.3.3
Final Visit (discharge day from clinic) ...............................................................49
9.3.4
Early Termination..............................................................................................50
9.3.5
Follow-up Visit.................................................................................................. 50
9.4 
Biological Sample Retention and Destruction .......................................................... 50
9.5 
Blood Volume .........................................................................................................51
9.6 
CSF Volume ............................................................................................................ 51


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CONFIDENTIAL 
9.7
Definitions...............................................................................................................51
9.7.1
PTE....................................................................................................................51
9.7.2
AE .....................................................................................................................51
9.7.3
Additional Points to Consider for PTEs and AEs................................................51
9.7.4
SAEs..................................................................................................................53
9.7.5
Severity of PTEs and AEs..................................................................................54
9.7.6
Causality of AEs................................................................................................ 54
9.7.7
Relationship to Study Procedures.......................................................................54
9.7.8
Start Date ........................................................................................................... 55
9.7.9
Stop Date...........................................................................................................55
9.7.10 Frequency ..........................................................................................................55
9.7.11 Action Concerning Study Medication ................................................................. 55
9.7.12 Outcome ............................................................................................................ 55
9.8 
Procedures ............................................................................................................... 56
9.8.1
Collection and Reporting of AEs ........................................................................ 56
9.8.2
Collection and Reporting of SAEs...................................................................... 57
9.8.3
Reporting of Abnormal LFT ..............................................................................57
9.9 
Follow-up of SAEs .................................................................................................. 58
9.9.1
Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities..... 58
10.0 
STUDY-SPECIFIC COMMITTEES .............................................................................58
11.0 
DATA HANDLING AND RECORDKEEPING ............................................................ 58
11.1 
CRFs (Electronic).................................................................................................... 58
11.2 
Record Retention ..................................................................................................... 59
12.0 
STATISTICAL METHODS..........................................................................................60
12.1 
Statistical and Analytical Plans ................................................................................60
12.1.1 Analysis Sets......................................................................................................60
12.1.2 Analysis of Demographics and Other Baseline Characteristics ...........................60
12.1.3 PK Analysis ....................................................................................................... 61
12.1.4 Safety Analysis .................................................................................................. 61
12.2 
Interim Analysis and Criteria for Early Termination ................................................ 62
12.3 
Determination of Sample Size .................................................................................. 62
13.0 
QUALITY CONTROL AND QUALITY ASSURANCE............................................... 62
13.1 
Study-Site Monitoring Visits ...................................................................................62
13.2 
Protocol Deviations.................................................................................................. 62
13.3 
Quality Assurance Audits and Regulatory Agency Inspections ................................63
14.0 
ETHICAL ASPECTS OF THE STUDY........................................................................63
14.1 
IRB and/or IEC Approval ........................................................................................ 64
14.2 
Subject Information, Informed Consent, and Subject Authorization .........................64


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14.3
Subject Confidentiality ............................................................................................66
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy .................................66
14.4.1 Publication and Disclosure ................................................................................. 66
14.4.2 Clinical Trial Registration.................................................................................. 67
14.4.3 Clinical Trial Results Disclosure ........................................................................67
14.5
Insurance and Compensation for Injury....................................................................67
15.0 
REFERENCES.............................................................................................................. 68
LIST OF IN-TEXT TABLES
Table 1
Single-Dose Visit Schedule................................................................................21
Table 2 
Multiple Dose Visit Schedule.............................................................................22
Table 3 
Prohibited Medications and Dietary Products.....................................................28
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo ...................... 32
Table 5 
Planned Single and Multiple Dose Levels by Cohort..........................................33
Table 6 
Collection of Blood Samples for PK Analysis in Single-Dose Cohorts ...............41
Table 7 
Collection of Blood Samples for PK Analysis in Multiple-Dose Cohorts............ 42
Table 8 
Collection of CSF Samples for PK Analysis in Single-Dose Cohorts.................. 43
Table 9 
Collection of CSF Samples for PK Analysis in Multiple-Dose Cohorts ..............43
Table 10 
Clinical Laboratory Tests...................................................................................45
Table 11 
Windows for PK Blood Sample Collection ........................................................ 63
LIST OF IN-TEXT FIGURES
Figure 1 Study Schema .............................................................................................................19
LIST OF APPENDICES
Appendix A: Schedule of Study Procedures .............................................................................. 69
Appendix B: Responsibilities of the Investigator.....................................................................75
Appendix C: Investigator Consent to Use of Personal Information .......................................... 76


CVN766
Study No. CVN766-101
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CONFIDENTIAL
2.0
STUDY SUMMARY
Name of Sponsor(s):
Cerevance, Inc.
Compound:
CVN766
Title of Protocol: A Phase 1, Randomized, Double-Blind, 
Placebo-Controlled, Safety, Tolerability, and 
Pharmacokinetic Study of Escalating Single and Multiple 
Doses of CVN766 in Healthy Subjects 
IND No.: 
EudraCT No.:
Not Applicable
Study Number: CVN766-101
Phase: 1
Study Design:
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in 
healthy subjects with concurrent PK sampling from blood plasma, urine, and cerebrospinal fluid. The overall study 
design is outlined below: 
  
Part 1: Single-Dose Regimen and Fasted-Fed Crossover
For the single-dose regimen, approximately 40 healthy male or female subjects will be enrolled in 1 of 5 single-dose 
cohorts (designated as S1 through S5, respectively) in an ascending fashion. An optional 8 subject (Cohort S3a)
may be added in parallel with Cohort S3. Cohort S3a dose level will be consistent with Cohort S3 (45 mg planned) 
in a fasted condition only and without lumbar puncture, aligned with the Schedule of Procedures (Appendix A) and
other SAD Cohorts. Each cohort will consist of 8 subjects randomized to CVN766 or placebo. In each cohort, 6 
subjects will receive a single oral dose of CVN766 suspension, and 2 subjects will receive a matching placebo 
suspension under overnight fasted conditions. Subjects will remain fasted for 4 hours post-dose. Consumption of 
water is permitted as desired except for 1 hour before and after administration of Study Drug. Sentinel dosing (1 
subject to receive CVN766 and 1 subject to receive placebo) will be used in each cohort to ensure adequate safety 
and tolerability evaluation prior to administering CVN766 or placebo to the remainder of the subjects within the 
cohort. After blinded review by the Investigator of 24-hour post-dose adverse event listings (as applicable) from the 
sentinel group, the Investigator will advise the sponsor on the acceptability of enrolling the remaining 6 subjects in 
each cohort. In the event that a safety signal emerges in the sentinel group, a Safety Review Group (SRG) meeting 
may be required as requested by Investigator or Sponsor. To accommodate the lumbar puncture in the S3 fasted
cohort, the remaining 6 subjects' dosing may be staggered every two days after the sentinel group. The planned dose 
levels will be 5, 15, 45, 125, and 250 mg CVN766.  The SRG will review all available blinded safety, tolerability, 
clinical laboratory results (minimally including samples collected from subjects through 72-hours post-dose), and
available pharmacokinetic (PK) data prior to all dose escalations and after the completion of all subjects in a cohort. 
If Cohort S3a (optional cohort) is enrolled and completed prior to Cohort 3, the SRG may determine dose escalation 
to Cohort S4 after evaluating data from Cohort 3a alone. Each following dose level may be higher, lower, or remain 
the same as the preceding cohort, dependent on the recommendation of the SRG. 
Additional cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety and tolerability 


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Page 10 of 76
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01 June 2022
CONFIDENTIAL 
of CVN766. For example, if Cohort S5 is well-tolerated, additional cohorts with higher dose levels may be 
considered. Such additional cohorts will follow the same schedule of events as for Cohorts S1 through S5.
Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary to fully 
characterize the PK profile of CVN766. 
To assess the effect of food on CVN766 bioavailability in suspension formulation, the single-dose administration 
will be repeated in a single cohort (S3) after ingestion of a standardized high-fat, high-calorie meal according to 
FDA Guidance for Industry (Food-effect bioavailability and fed bioequivalence studies, Dec 2002). Once the safety 
of the Cohort S3  dose level has been assessed, the  Cohort S3  subjects will return to the clinic (no sooner than 14 
days after their prior dose, or at least 4 half-lives, has lapsed based on preliminary PK data, whichever is longer). 
They will receive the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish 
at least approximately 85% of their breakfast within 30 minutes and receive an investigational product 30 minutes 
(± 5 minutes) after beginning the meal. Sentinel dosing will not be required for subjects returning to the clinic for 
the fed regimen. If the CVN766 PK parameters in the fasted S3 cohort reveal poor absorption with inconclusive 
results, the fed cohort will be deferred until a higher dose level.   
Subjects for all cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit for safety and 
PK assessments. On Day 1, subjects will undergo safety monitoring and PK sampling from blood plasma through 
72 hours post-dose and, for Cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose. The total 
confinement period will be 4 nights unless extended at the discretion of the Investigator, e.g., for monitoring and/or 
management of AEs. Follow-up assessments will occur on approximately Days 8 and 14 and +21 and +28 for Cohort
S3. 
A summary of the single-dose regimen visit schedule is presented below:  
Screening a
Inpatient  
Check-in 
Dosing, PK, 
CSF & Safety 
Assessments b
Inpatient PK,  
Safety and 
Lumbar 
Puncture Site 
Assessments 
(S3 fasted) 
Inpatient 
Discharge c 
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d 
 
Day -28 to -2 
Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8
±1 day 
Day 14
±2 days 
(a) Screening will occur at study entry. S3 subjects returning for the “Fed” repetition of the single-dose 
regimen will not undergo Screening assessments except as required on Day -1. 
(b)
CSF collection will apply only to Cohort S3 (fasted). 
(c)
Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs.
(d)
The final follow-up assessment will occur by telephone unless abnormal, clinically significant (CS)
findings were observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation.
Part 2: Multiple-Dose Regimen 
For the multiple-dose regimen, approximately 24 healthy male and female subjects aged 18 to 55 will be enrolled 
in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. The dose 
levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-dose 
Cohorts M1 through M3, respectively. Each multiple-dose cohort will consist of 8 subjects randomized to CVN766 
or placebo, whereby 6 subjects will receive a daily oral dose of CVN766, and 2 subjects will receive matching 
placebo for 7 days. Dosing will be administered in the fasting state; the SRG can change this if exposure is higher 
in the fed state. The planned dosing duration for the multiple-dose cohorts is 7 days. However, the duration may be 
gest steady-state will not be achieved 
within 6 days of daily dosing. For each dose on intensive PK sampling days (first and last days of dosing, e.g., Days 
1 and 7), subjects will remain fasted for 4 hours post-dose. On other dosing days (Days 2-6), subjects will remain 
fasted for 1-hour post-dose. Consumption of water is permitted as desired except for 1 hour before and after 
administration of Study Drug. Unlike the single-dose regimen, sentinel dosing within cohorts is not required in the 
multiple-dose regimen. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all safety, tolerability, and 
clinical laboratory results for the fasting drug administration to single-dose Cohort S3 or Cohort S3a (minimally 


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including samples collected through Day 4) and available PK data. For each multiple-dose cohort after the first, the 
actual choice of dose level may be modified by the SRG after the available blinded safety, tolerability, clinical 
laboratory results, and PK data in the preceding multiple-dose and corresponding single-dose cohorts (i.e., multiple-
dose Cohort M2 will not initiate until the data review for multiple-dose Cohort M1 and single-dose Cohort S4 is 
complete). Each subsequent dose level may be higher, lower, or remain the same as the preceding.
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully characterize the safety
and tolerability of CVN766. Such additional cohorts will follow the same schedule of events as for prior multiple-
dose cohorts.  Additional/Alternative PK timepoints may be implemented if the SRG determines this is necessary 
to fully characterize the PK profile of CVN766. 
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and remain in the unit 
for the duration of the dosing period and for at least 48 hours after the last dose for safety and PK assessments before 
discharge. On treatment Days 1 and 7, subjects will undergo safety monitoring and PK sampling from blood plasma 
through 48 hours post-dose and, in Cohort M1 only, from urine through 24 hours post-dose. Additionally, Cohorts
M1 and M2, on treatment Day 7 (or last day of dosing, if extended beyond Day 7), subjects will undergo additional 
PK sampling from CSF via lumbar puncture at 3 hours post-dose. However, if the SRG determines additional PK 
sampling from CSF via lumbar puncture is not necessary for Cohort M2, the lumbar puncture may be omitted. 
Likewise, if needed to resolve questions arising from prior Cohorts’ data, subjects in Cohort M3 also may, at SRG 
discretion, undergo PK sampling from CSF via lumbar puncture, the choice of day (e.g., Day 1 or Day 7) and 
sampling time to be decided by SRG. Subjects in MAD cohorts may be asked to return to the clinic for an additional 
PK sample 3 days after the last dose (e.g., Day 10) depending on emerging PK data, i.e., t½). The total confinement 
period will be 9 nights unless extended for additional dosing days or management of AEs. Follow-up assessments 
will occur approximately 7 and 14 days after the final dose. 
A summary of the multiple-dose regimen visit schedule is presented below: 
Screening 
Inpatient 
Check-in 
Dosing, PK, 
CSF, & Safety 
Assessments  a
PK / Safety 
Assessments & 
inpatient 
discharge b 
Follow-Up Outpatient 
Visits c 
Follow-Up Call d
Day -28 to -2 
Day -1 
Days 1-7 e 
1 and 2 days after 
last dose (e.g., 
Days 8-9) 
3 days ±0 after last dose 
(e.g., Day 10) &
7 days ± 1 after last dose 
(e.g., Day 14)
14 days ±2 after last 
dose (e.g., Day 21) 
(a) CSF sampling is planned on Day 7 in Cohorts M1 and M2 (CSF sampling for Cohort M2 may be omitted
at the discretion of the SRG). Cohort M3 also may, at SRG discretion, undergo PK sampling from CSF, 
the choice of day and sampling time to be decided by SRG.  
(b)
Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or, if 
necessary, to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after last dose (e.g., Day 
10) may be omitted at Investigator’s discretion. 
(d)
The Follow-up Visit will occur by telephone unless abnormal, clinically significant (CS) findings are 
observed upon discharge. In these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to 14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f) 
Urine sampling will occur on Day1 and Day 7 in Cohort M1. 
Safety Review Group (SRG) 
The SRG will comprise of the Investigator, Medical Monitor, Cerevance Responsible Medical Officer and may 
include other Cerevance representatives. A pharmacokineticist and other subject matter experts may participate as 
needed. The SRG will be responsible for the ongoing review of safety, tolerability, clinical laboratory results, and 
available PK data and deciding: 
1. Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in single-
dose cohorts (based on a review of available data, including at least 72 hours post-dose safety data and 


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clinical laboratory results from a minimum of 5 subjects in the current cohort),  
2.
Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or higher) in 
multiple-dose cohorts (based on a review of available data, including at least 48 hours post 7th dose safety 
data from a minimum of 5 subjects in the current cohort), 
3.
Add additional dose cohort(s) in either the single- or multiple-dose studies,
4. Increase the duration of dosing in the multiple-dose cohorts from 7 days to 14 days, 
In addition, if 2 or more subjects in a single cohort experience the same type of serious or medically significant 
event, further dosing will be withheld until the SRG investigates the events. Based on this assessment, the SRGwill 
determine if the study should be terminated or continued and whether modification of planned dose levels and/or 
implementation of additional safety monitoring is indicated.   
Primary Objective: 
To characterize the safety and tolerability profile of escalating dose levels of CVN766 suspension when 
administered as a single oral dose or daily oral doses for 7 days in healthy subjects and determine the recommended 
phase 2 dose (RP2D). 
Secondary Objectives: 
• To characterize the single-dose PK profile of CVN766 in plasma and CSF 
• To characterize the multiple-dose PK profile of CVN766 in plasma and CSF 
• To assess the effect of food on the bioavailability of CVN766 
Exploratory Objectives: 
• To explore possible drug metabolic enzyme and transporter polymorphisms that may contribute to variability in 
CVN766 PK, pharmacodynamics, or safety 
Subject Population: Healthy male and female subjects 18 to 55 years old 
Number of Subjects: 
Each dose cohort: 8 subjects (6 active:2 placebo) 
Estimated total: 64 subjects  
(5 single-dose cohorts, 3 multiple-dose cohorts)  
Number of Sites:
2 (Australia) 
Dose Level(s):
Planned single-dose levels are placebo, 5 mg, 15 mg, 45 
mg, 125 mg, and 250 mg CVN766. 
Planned multiple dose levels are placebo, 45 mg, 125 mg, 
and 250 mg CVN766. 
Route of Administration:
Oral 
Duration of Treatment: 
Single or daily oral doses for up to 7 days (+7 days as 
necessary to reach steady-state and as required by  Safety 
Review Group).  
Period of Evaluation:
Screening Period: up to 28 days 
Treatment Period: 1-7 days (+7 days, as necessary). 
Food Effect washout period (for select cohort only): 
at least 14 days 
Follow-up Period: approximately 14 days 
Total Duration:  
 Single-dose cohorts: approximately 6 weeks 
 Food effect cohort: approximately 8 weeks 
 Multiple-dose cohorts: approximately 7 weeks 
Main Criteria for Inclusion:
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Healthy male and female subjects who are 18 to 55 years of age, inclusive and have a body mass index (BMI) 
between 18.0 and 32.0 kg/m2 inclusive at Screening.
A complete list of inclusion criteria is provided in Section 7.1. 
Main Criteria for Exclusion:
Subjects have a known hypersensitivity to any component of the formulation of CVN766. Subjects have evidence 
of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, 
urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, psychiatric disorder, or other 
abnormality that may impact the ability of the subject to participate or potentially confound the study results. Any 
finding in the subject’s medical history, physical examination, or safety laboratory tests gives reasonable suspicion 
of a condition that might interfere with the conduct or interpretation of the study. 
A complete list of exclusion criteria is provided in Section 7.2.  
In addition, subjects may not use any excluded medications (including oral contraceptives as listed in Table 3), 
supplements, or food products. Concomitant medications and dietary products to be excluded are listed in Table 3.
Main Criteria for Evaluation and Analyses:
- Safety:  
Safety parameters will include AEs, clinical laboratory results, vital signs, physical examinations, and 
electrocardiogram (ECG). AEs will be collected from signing the informed consent form (ICF) up until dosing on 
Day 1 as pretreatment events (PTEs), and any event that occurs from dosing until 14 days after the last dose will be 
captured as an AE. Vital signs will be recorded at Screening, Inpatient Check-in (Day -1), and throughout the dosing 
period. Vital signs will include tympanic body temperature measurement, blood pressure, respiration rate, and pulse 
(beats per minute [bpm]). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline 
(Check-in Day -1) 15 minutes apart (the average will be used to determine eligibility). Heart rate and blood pressure 
will be measured after at least 5 minutes supine and again at 2 minutes after standing for all scheduled timepoints.
Standard 12-lead ECGs will be recorded at Screening, Inpatient Check-in (Day -1), and periodically throughout the 
dosing period. Triplicate ECGs will be taken at each timepoint. 
A complete list of safety assessments is provided in Section 9.1, and the full Schedule of Study Procedures is 
provided in Appendix A. 
- PK:  
The plasma PK parameters are used as PK endpoints to determine drug exposure at each dose and facilitate dose 
escalations.  
Plasma samples will be collected for the determination of concentrations of CVN766 throughout the study as 
prescribed in the Schedule of Study Procedures (Appendix A). Cerebrospinal fluid (CSF) samples will be collected 
for the determination of concentrations of CVN766 as described in Section 9.6 and the Schedule of Study Procedures 
(Appendix A). PK sampling timepoints may be modified or added based on emerging PK data to most appropriately 
characterize the PK profile of CVN766 as determined by the SRG.
PK parameters of CVN766 will be derived using noncompartmental analysis methods from the concentration-time 
data for all evaluable subjects. Actual sampling times, rather than scheduled sampling times, will be used in all 
computations involving sampling times. The following PK parameters will be determined from concentrations of 
CVN766 in plasma: Cmax, AUC from time 0 to the last quantifiable concentration (AUCt), AUC from time 0 to 
infinity (AUC ), AUC from time 0 to 24 hours (AUC24), time to reach Cmax (tmax), terminal elimination rate constant 
z), terminal elimination half-life (t1/2z), apparent clearance (CL/F), and apparent volume of distribution (Vz/F). 
Multiple-dose PK will also include AUC over the dosing interval (AUCtau), apparent clearance at steady state 
(CL/Fss), apparent volume of distribution at steady state (Vz/Fss), steady-state nadir concentrations, and 
accumulation ratios  
The PK parameters to be determined from concentrations of CVN766 in CSF will include plasma: CSF ratio 
by time point.  
- Pharmacogenomics: 
One whole blood sample will be collected at pre-dose on Day 1 for pharmacogenomic analysis; this will only be 
collected once per subject. Two whole blood samples will be collected at pre-dose on Day 1 and at multiple 
timepoints post-dose for ribonucleic acid (RNA) pharmacogenomic analysis. The pre-dose RNA blood samples 


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should be collected under fasted conditions and prior to any other blood collection. The samples will be stored for 
no longer than 15 years after completion of the CVN766 study and/or until the drug development of CVN766 is no 
longer actively pursued by Cerevance or its collaborators. No samples will be stored for longer than permitted by 
the applicable law, and samples will be destroyed upon notification from Cerevance. “Stored samples” in this context 
are defined as samples that are double coded (the samples are stripped of all personally identifying information, but 
key links the samples to the clinical data collected from the sample donor) and are used in the analysis of 
investigational drug or related drug.
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; eligible subjects sign 
the ICF, which outlines the retention of pharmacogenomic and genotyping analysis in order to participate in this 
study. DNA samples will be collected and may be used to evaluate drug metabolic enzyme and transporter 
polymorphisms that may contribute to the variability in the PK of CVN766. Also, since pharmacogenomics is an 
evolving science, many genes and their functions are not yet fully understood. Future data may suggest a role of 
some of these genes in drug response, which may lead to additional hypothesis-generating exploratory research and 
diagnostic development on stored samples. 
- Endpoints: 
The primary endpoints of this study will be the following: percentage of subjects who experience at least one 
treatment-emergent adverse event (TEAE); percentage of subjects with abnormal and CS safety laboratory, vital 
signs, or ECG test results at least once post-dose.  
The secondary endpoints will be the following plasma PK parameters of CVN766: Cmax, AUC24, AUC , t1/2z, 
AUC from time 0 to end of the dosing interval, accumulation ratio, time to steady-state, steady-state Cmax, and 
steady-state Cmin. 
The additional endpoints may include the following plasma PK parameters of CVN766: tmax, CL/F, Vz/F, CL/Fss, 
Vz/Fss, and plasma: CSF ratio. 
Exploratory endpoints may include characterization of metabolic enzyme and transporter polymorphisms and/or 
Statistical Considerations: 
Safety: 
AEs will be presented in listings, and TEAEs will be summarized. Individual results of laboratory tests (hematology, 
chemistry, and urinalysis) will be recorded at baseline and post-dose, and changes from baseline will be summarized 
using shift tables. Individual vital signs will be recorded, and observed values and changes from baseline will be 
summarized. Individual results of quantitative ECG parameters from the 12-lead safety ECGs will be listed, and 
observed values and changes from baseline will be summarized. All summaries will be performed by placebo, each 
CVN766 dose level (fasted and fed separately), and CVN766 single-dose overall, and separately CVN766 multiple-
dose cohorts overall. Placebo data will be pooled across single-dose cohorts and separately pooled across multiple-
dose cohorts. Physical exam findings will be presented in data listings. 
PK Measures: 
Concentrations of CVN766 in plasma and CSF will be summarized by dose over each scheduled sampling time 
using descriptive statistics. Individual plasma and CSF concentration data versus time will be presented in a data 
listing. Individual and mean plasma and CSF concentration data will be presented graphically. 
PK parameters of CVN766 will be summarized by dose using descriptive statistics. Dose proportionality will be 
assessed graphically and using a power model. 
The concentrations of CVN766 in plasma and CSF will be compared. 
Sample Size Justification:  
The sample size chosen is considered sufficient for evaluating the safety, tolerability, and PK of each cohort. The 
sample size was not based on statistical power considerations. 
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3.0
STUDY REFERENCE INFORMATION
3.1
List of Abbreviations
z
terminal elimination rate constant 
AE
adverse event 
ALT
alanine aminotransferase
AST 
aspartate aminotransferase 
AUC
area under the plasma concentration-time curve 
AUC24
area under the plasma concentration-time curve from time 0 to 24 hours  
AUC
area under the plasma concentration-time curve from time 0 to infinity
AUCt
area under the plasma concentration-time curve from time 0 to the last 
quantifiable concentration  
AUCt 
area under the plasma concentration-time curve over the dosing interval (t)
BMI 
body mass index 
CL/F
apparent clearance after extravascular administration 
CL/Fss
apparent clearance after extravascular administration at steady state
 
 
Cmax 
maximum observed plasma concentration
Cmin
minimum observed plasma concentration 
CNS 
central nervous system 
CS 
clinically significant
CSF
cerebrospinal fluid 
ECG
electrocardiogram 
eCRF
electronic case report form 
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone 
FT4 
free T4 
GCP 
Good Clinical Practice 
GGT
-glutamyl transferase 
HBsAg 
hepatitis B surface antigen 
hCG 
human chorionic gonadotropin
HCV
hepatitis C virus
HED
human-equivalent dose 
ICF
informed consent form 
ICH 
International Council on Harmonisation 
IEC
independent ethics committee
PP
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INR
international normalized ratio
IRB 
institutional review board 
K2EDTA 
dipotassium ethylenediamine tetraacetic acid 
LFT
liver function test
MAD
multiple-ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
MRSD
maximum recommended starting dose
NCS 
not clinically significant 
NOAEL 
no-observed-adverse-effect-level 
Ox1R
orexin 1 receptor
Ox2R
orexin 2 receptor
PK
pharmacokinetic 
PRL
prolactin
PT 
preferred term 
PTE
pretreatment event 
QTcB 
QT interval with Bazett’s correction method
QTcF
QT interval with Fridericia’s correction method 
RNA
ribonucleic acid
RO 
receptor occupancy
SAE 
serious adverse event
SAD
single-ascending dose
SAP
statistical analysis plan 
SOC 
system organ class
SRG 
Safety Review Group 
SUSARs
suspected unexpected serious adverse reactions
t1/2z
terminal elimination half-life
TEAE
treatment-emergent adverse event
tmax
time to reach Cmax 
ULN
upper limit of normal 
Vz/F 
apparent volume of distribution after extravascular administration
Vz/Fss 
apparent volume of distribution after extravascular administration at steady 
state
WHO 
World Health Organization
 


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4.0
INTRODUCTION
4.1
Background
The neuropeptide orexin, also known as hypocretin, is produced exclusively in the orexigenic 
neurons in the hypothalamus. There are two forms of orexin, Orexin-A, and orexin-B, alternatively 
spliced from the same gene, HCRT.   There are two orexin receptors, orexin 1 receptor (Ox1R) 
and orexin 2 receptors (Ox2R), both of which are G-protein coupled receptors. Both orexin-A and 
orexin-B can bind to either receptor and in each case, agonist binding results in an increase in 
intracellular calcium levels. However, while orexin-A is equipotent at both receptors, orexin-B 
shows a 10-fold selectivity for Ox2R.  
Ox1R is selectively expressed in key brain areas relating to psychiatric disorders. Ox1R-expressing 
neurons in the bed nucleus of the stria terminalis, amygdala, locus coeruleus, raphe nucleus, and 
the ventral tegmental area are important in regulating emotions of stress, anxiety, motivation, and 
reward. CVN766 is a potent and highly selective small-molecule Ox1R antagonist with no 
significant off-target activity. Nonclinical PK and toxicology studies with CVN766 and other 
Ox1R antagonists have established their pharmacological characteristics and probable safety 
profile.
Ox2R is expressed in some overlapping areas, including the raphe nucleus, and ventral tegmental 
area, but also in areas important to arousal and sleep regulation, including the tuberomammillary 
nucleus. 
The widely used sleep aid suvorexant (Belsomra®), approved for use in Australia, is a dual Ox1R 
and Ox2R antagonist, but its sleep-inducing effects are generally attributed to its activity on Ox2R. 
A second dual Ox1R and Ox2R antagonist, lemborexant, appeared safe and effective in clinical 
studies, has been approved in many countries worldwide, and has been submitted for marketing 
authorization in Australia.  
Clinical effects to be expected of a selective Ox1R antagonist remain uncertain. CVN766 has not
yet been studied in humans. Other selective Ox1R antagonists have been reported in early-stage 
human clinical trials, notably JNJ-61393215 (ClinicalTrials.gov Identifier: NCT04080752; 
Salvadore et al., 2020) and ACT-539313 (NCT01954589; Kaufmann et al., 2020; Kaufmann et 
al., 2021). Both drugs were well tolerated and deemed safe for investigational use, the most 
common AEs being somnolence and mild headache.  
4.2 
Rationale for the Proposed Study 
CVN766 is a highly selective orexin-1 receptor (Ox1R) antagonist and may have utility as a 
treatment for psychiatric disorders including schizophrenia, panic disorder and anxiety, and 
addiction. Its safety and PK profile have been preliminarily established in nonclinical toxicology 
studies. The present study will be the first conducted in humans with CVN766 and will examine 
the compound's safety, tolerability, and PK in healthy subjects. 
Nonclinical pharmacology, toxicity, and pharmacokinetic (PK) studies support the proposed 
escalating single- and multiple-dose study of CVN766 in healthy subjects with a starting dose of 
5 mg. Section 6.2 outlines the justification for the planned dose ranges.  
 


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5.0
STUDY OBJECTIVES AND ENDPOINTS
5.1
Objectives
5.1.1 Primary Objective
 To characterize the safety and tolerability profile of escalating dose levels of CVN766
suspension when administered as a single oral dose or daily oral doses for 7 days in healthy 
subjects
5.1.2 Secondary Objectives  
 To characterize the single-dose PK profile of CVN766 in plasma, and CSF 
 To characterize the multiple-dose PK profile of CVN766 in plasma, and CSF 
 To assess the effect of food on the bioavailability of CVN766 in the current formulation 
5.1.3 Exploratory Objectives
 To explore possible drug metabolic enzyme and transporter polymorphisms that may 
contribute to variability in CVN766 PK, pharmacodynamics, or safety 
5.2
Endpoints
5.2.1 Primary Endpoints
Percentage of subjects who experience at least one treatment-emergent adverse event 
(TEAE)
Percentage of subjects with abnormal and clinically significant (CS) safety laboratory test 
results at least once post-dose 
 Percentage of subjects with abnormal and CS electrocardiogram (ECG) test results at least 
once post-dose 
 Percentage of subjects with abnormal and CS vital sign measurements at least once post-
dose 
5.2.2 Secondary Endpoints 
 Single-dose plasma PK parameters of CVN766, including time to maximum plasma 
concentration (Tmax), area under the plasma concentration-time curve from time 0 to 24 
(AUC24) and time 0 to 
-life (t1/2z) 
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Multiple-dose plasma PK parameters of CVN766 including Cmax, AUC from time 0 to the 
end of the dosing interval, t1/2z, accumulation ratio, time to steady-state, steady-state Cmax, 
and steady-state Cmin
Single-dose and multiple-dose CSF concentrations and CSF: plasma ratios of CVN766
5.2.3
Additional Endpoints
Change from baseline in safety laboratory and ECG test results and vital signs
Additional plasma PK parameters of CVN766, i.e., CL/F and Vz/F
Characterization of metabolic enzyme and transporter polymorphisms
6.0
STUDY DESIGN AND DESCRIPTION
6.1
Study Design
This is a Phase 1 ascending study in healthy subjects. Figure 1 provides a schematic illustration.
Figure 1 Study Schema
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6.1.1
Part 1: Single-Dose Regimen and Fasted-Fed Crossover
Approximately 40 subjects will be enrolled in 1 of the 5 single-dose cohorts (designated as S1 
through S5, respectively) in an ascending fashion. An optional Cohort 3a may be added in parallel 
to SC3 for additional safety and tolerability evaluation. Cohort S3a dose level will be consistent 
with Cohort S3 (45 mg planned) in a fasted condition only and without lumbar puncture, aligned 
with the Schedule of Procedures (Appendix A) and other SAD cohorts.  Dose escalation will only 
occur after a fully blinded review of all available safety, tolerability, clinical laboratory results 
(minimally including samples collected from subjects through 72-hours post-dose), and available 
PK data, including at least a 72-hour follow-up from a minimum of 5 subjects of the most recent 
cohort. 
The planned dose levels are provided in Table 5. Each cohort will consist of 8 subjects randomized 
to CVN766 or placebo, whereby 6 subjects will receive a single dose of CVN766 and 2 subjects 
will receive a matching placebo under overnight fasted conditions.  
Sentinel dosing (1 subject to receive CVN766 and 1 subject to receive placebo) will be used in 
each cohort to ensure adequate safety and tolerability evaluation prior to administering CVN766 
to the remainder of the subjects within the cohort. After a blinded review of 24-hour post-dose
safety and tolerability data, the remaining 6 subjects of each cohort may be dosed, provided that 
the adverse event (AE) profile of CVN766 in the first 2 subjects is considered acceptable. 
Subjects for all cohorts (including optional Cohort S3a) will be admitted to the study unit 1 day 
prior to dosing and remain in the unit for safety and PK assessments at least 72 hours after dosing. 
On Day 1, subjects will undergo safety monitoring (including labs, physical exam, neurological 
exam, cardia telemetry at 12-hours pre-dose), and PK sampling from blood plasma through 72 
hours post-dose.  In addition, for Cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours 
post-dose. For subjects participating in the SAD cohorts, the total confinement period will be 4 
nights unless extended for management of AEs at the discretion of the Investigator. Follow-up 
assessments will occur on approximately Days 8 and 14. 
To assess the effect of food on bioavailability of CVN766 in suspension formulation, single-dose 
administration will be repeated in a single cohort after ingestion of a standardized high-fat high-
calorie meal according to FDA Guidance for Industry (Food-effect bioavailability and fed 
bioequivalence studies, Dec 2002). Once the safety of the S3 Cohort dose level has been assessed, 
the S3 Cohort subjects will return to the clinic (no sooner than 14 days after their prior dose, or at 
least 4 half-lives has lapsed based on preliminary PK data, whichever is longer) and will receive 
the same dose as before, administered after ingesting a standardized breakfast. Subjects will finish 
at least approximately 85% of their breakfast within 30 minutes and will receive an investigational 
product 30 minutes (± 5 minutes) after beginning the meal. Sentinel dosing will not be required 
for subjects returning to the clinic for the fed regimen.  If the CVN766 PK parameters in the fasted 
S3 Cohort reveal poor absorption with inconclusive results, the fed cohort will be deferred until a 
higher dose level. 
An outline of the single-dose study visit schedule is included in Table 1. A Schedule of Study 
Procedures is listed in Appendix A. 
 


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Table 1
Single-Dose Visit Schedule
Screening a
Inpatient  
Check-in 
Dosing, PK,
CSF & Safety 
Assessments b
Inpatient PK 
& Safety 
Assessments 
Inpatient 
Discharge c
Follow-Up 
Outpatient 
Visit 
Follow-Up 
Call d
Day -28 to -2 
Day -1 
Day 1 
Day 2-4 
Day 4 
Day 8 
±1 day 
Day 14 
±2 days 
(a) Screening will occur at study entry. Subjects returning for the “Fed” repetition of the single-dose regimen 
will not undergo Screening assessments except as required at Day -1. 
(b)
CSF collection will apply only to Cohort S3 (fasted).
(c) Discharge from the clinic may be delayed if necessary to continue monitoring for resolution of AEs. 
(d)
The final follow-up assessment will occur by telephone unless abnormal CS findings are observed upon 
discharge. In these cases, subjects must return to the clinic for re-evaluation. 
6.1.2
Part 2: Multiple-Dose Regimen
For the multiple-dose regimen, approximately 24 subjects will be enrolled in 1 of the 3 multiple-
dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. Dosing will 
be administered in the fasting state; this can be changed by the SRG if exposure is found to be 
higher in the fed state. The dose levels planned to be studied in the multiple-dose regimen (M1 
through M3) are provided in Table 5. Each multiple-dose cohort will consist of 8 subjects 
randomized to CVN766 or placebo, whereby 6 subjects will receive a daily dose of CVN766, and 
2 subjects will receive matching placebo for 7 days. However, the duration may be increased to 
14 days at the discretion of the safety review group (SRG) if preliminary PK data suggest steady-
state will not be achieved within 6 days of daily dosing. Unlike the single-dose regimen, sentinel 
dosing within cohorts is not required in the multiple-dose regimen.
Subjects for all multiple-dose cohorts will be admitted to the study unit 1 day prior to dosing and 
remain in the unit for the duration of the dosing period and for at least 48 hours after the last dose 
for safety and PK assessments before discharge. On treatment Days 1 and 7, subjects will undergo 
safety monitoring and PK sampling from blood plasma through 48 hours post-dose and, in Cohort
M1 only, from urine through 24 hours post-dose. In Cohorts M1 and M2, on treatment Day 7 (or 
last day of dosing, if extended beyond Day 7),. subjects will undergo additional PK sampling from 
CSF via lumbar puncture at 3 hours post-dose. If the SRG determines additional PK sampling from 
CSF via lumbar puncture is not necessary for Cohort M2, the lumbar puncture may be omitted. 
Likewise, if needed to resolve questions arising from prior Cohorts’ data, subjects in Cohort, 
subjects in Cohort M3 also may, at SRG discretion, undergo PK sampling from CSF via lumbar 
puncture, the choice of day (e.g., Day 1 or Day 7) and sampling time to be decided by SRG. 
Subjects in MAD cohorts may be asked to return to the clinic for an additional plasma PK sample 
3 days after the last dose (e.g., Day 10) depending on emerging PK data, i.e., t½. The total 
confinement period will be 9 nights unless extended for additional dosing days or management of 
AEs. Follow-up assessments will occur approximately 7 and 14 days after the final dose. A 
summary of multiple-dose study visits is included in Appendix A.


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Table 2 Multiple Dose Visit Schedule
Screening
Inpatient 
Check-in
Dosing, PK, 
CSF, & Safety 
Assessments  a,f 
PK / Safety 
Assessments & 
inpatient discharge b 
Follow-Up Outpatient 
Visits c
Follow-Up Call d
Day -28 to -2 
Day -1 
Days 1-7 e
1 and 2 days after last 
dose (e.g. Days 8-9) 
3 days ±0 after last dose 
(e.g. Day 10) & 
7 days ± 1 after last dose 
(e.g. Day 14) 
14 days ±2 after 
last dose (e.g. Day 
21) 
(a)
CSF sampling is planned on Day 7 in Cohorts M1 and M2 (CSF sampling for Cohort M2 may be omitted at 
the discretion of the SRG). Cohort M3 also may, at SRG discretion, undergo PK sampling from CSF, the 
choice of day and sampling time to be decided by SRG.  
(b)
Discharge from the clinic is planned for Day 9 but may be delayed for additional dosing days or if necessary,
to continue monitoring for resolution of AEs. 
(c) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the visit 3 days after the last dose (e.g., 
Day 10) may be omitted at Investigator’s discretion. 
(d)
The Follow-up Visit will occur by telephone unless abnormal CS findings are observed upon discharge. In 
these cases, subjects must return to the clinic for re-evaluation. 
(e) Dosing duration may be increased to 14 days at the discretion of the SRG based on preliminary PK and 
projected time to steady-state. 
(f)
Urine sampling will occur on Day1 and Day 7 in Cohort M1. 
6.1.3 Dose Escalation  
The SRG will comprise the Investigator, Medical Monitor, Cerevance Responsible Medical 
Officer and may include other Cerevance representatives. A pharmacokineticist and other subject 
matter experts may participate as needed. The SRG will be responsible for the ongoing review of 
safety, tolerability, clinical laboratory results, and available PK data and deciding to:
 Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in single-dose cohorts (based on a review of available data, including at least 72 
hours post-dose safety data and clinical laboratory results from a minimum of 6 evaluable 
subjects in the current cohort),
Escalate to the next planned cohort or alternative dose levels (e.g., lower, intermediate, or 
higher) in multiple-dose cohorts (based on a review of available data, including at least 48 
hours post 7th dose safety data from a minimum of 6 evaluable subjects in the current 
cohort), 
 Add additional dose cohort(s) in either the single- or multiple-dose studies, 
 Increase the duration of dosing in the multiple-dose cohorts from 7 days to 14 days 
If 2 or more subjects in a single cohort experience the same type of serious or medically adverse 
event, further dosing will be withheld until the SRG investigates the events.  Based on this 
assessment, the SRG will determine if the study should be terminated or continued and whether 
modification of planned dose levels and/or implementation of additional safety monitoring is 
indicated.   


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For each cohort (including sentinel subjects, where applicable), the SRG will carefully review the 
available blinded safety, tolerability, clinical laboratory results, and available PK data to determine 
whether dosing should stop or continue (and, if continued, at what dose, including whether to 
repeat the previous dose), whether additional sequential dosing should be implemented in future 
cohorts or whether the blind should be broken to identify whether the subjects received CVN766 
or placebo. However, precautions must be taken not to unblind the study staff, including the 
Investigator.
If all doses are tolerated, then additional cohorts with higher doses may be considered. The actual 
choice of the subsequent dose level will occur after the full review of the available blinded safety, 
tolerability, clinical laboratory results, and available PK data in the preceding cohort. The 
subsequent dose level may be higher, lower, or remain the same as the prior dose level. If 
necessary, additional cohort(s) may be added to fully characterize the safety and tolerability of 
CVN766. 
Initiation of the multiple-dose regimen will only occur after a full blinded review of all available 
safety, tolerability, and clinical laboratory results for the fasting drug administration to single-dose 
Cohort S3 (minimally including samples collected through Day 4) and available PK data. For each 
multiple-dose cohort after the first, the actual choice of dose level may be modified by the SRG 
after a review of the available blinded safety, tolerability, and clinical laboratory results, and 
available PK data in the preceding multiple-dose and next-higher-dosage single-dose cohorts (i.e., 
multiple-dose Cohort M2 will not initiate until the data review for multiple-dose Cohort M1 and 
single-dose Cohort S4 is complete). Each subsequent dose level may be higher, lower, or remain 
the same as the preceding dose level. 
Additional multiple-dose cohort(s) may be added if deemed necessary by the SRG to fully 
characterize the safety and tolerability of CVN766. Such additional cohorts will follow the same 
schedule of events as for prior multiple-dose cohorts. Additional/Alternative PK timepoints may 
be implemented if the SRG determines this is necessary to fully characterize the PK profile of 
CVN766. 
All AEs reported during the Treatment Period, both within and across cohorts, up to the time of 
discharge, will be evaluated to assess the need for the subject and/or study termination in 
accordance with the prespecified criteria for discontinuation/termination (Section 6.3.1).  
Additionally, the SRG may decide not to escalate the dose for a particular cohort but rather 
administer the same or a lower dose level to the next cohort. Additional/ Alternative PK timepoints 
may be implemented if the SRG determines this is necessary to fully characterize the PK profile 
of CVN766. 
6.2 
Justification for Study Design, Dose, and Endpoints 
The study is double-blind and placebo-controlled to avoid subjective bias in assessing the safety 
and tolerability of CVN766. Dose escalation will be predicated on a review of available blinded 
safety, tolerability, and PK data from a minimum of evaluable 6 subjects from the prior Cohort. 


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The sponsor has selected the starting dose level considering the FDA Guidance for Industry 
(Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult 
Healthy Volunteers, 06 July 2005) and providing additional safety factors to the initial calculations 
based on the principles outlined in the guidance. The toxicity profile of CVN766 after oral dosing 
was examined in repeat dosing studies in rats and dogs. Scaling based on body surface area was 
conducted by multiplying the NOAELs for the most sensitive animal species by the appropriate 
conversion factors. Based on these calculations and applying a 10-fold safety margin below the 
NOAEL human-equivalent dose (HED), the maximum recommended starting dose (MRSD) for 
this first-in-human study is 167 mg for a 60 kg subject. The selected starting dose level is 5 mg.
The study's multiple-ascending dose (MAD) portion seeks to prepare for subsequent repeat dosing 
studies in subjects. Each MAD dose level will have been studied or exceeded in the SAD portion 
of the study before its use in a MAD cohort. 
Nonclinical toxicity study data provide a basis for calculating the maximum exposure level that 
can be presumed safe. Escalating to the HED of the NOAEL in the most sensitive animal species, 
the maximum dose for clinical use is 1670 mg/day.  
The projected t1/2z in animal species ranged up to 6.5 hours, so sample collection through Inpatient 
Discharge 72 hours post-dose is expected to correspond to more than 5 half-lives and is anticipated 
to be adequate to document elimination of CVN766. The study design allows for collecting 
additional PK samples at later timepoints if preliminary emerging PK results are indicated.  
AEs, physical exams, vital signs, ECG findings, and clinical laboratory results are used as safety 
assessments to determine dose tolerability and dose-limiting effects of CVN766. The plasma PK
and CSF parameters and PK endpoints will help elucidate the pharmacology of CVN766. 
Samples for DNA analysis will be collected and may be used to evaluate drug metabolic enzyme 
and transporter polymorphisms that may contribute to the variability in the PK of CVN766.
6.3 
Premature Termination or Suspension of Study or Investigational Site
6.3.1
Criteria for Premature Termination or Suspension of the Study
The study will be completed as planned unless new information or other evaluation regarding the 
safety of the study medication indicates an adverse change in the risk profile for the compound, 
such that the SRG or Institutional Review Board (IRB) considers the risk is no longer acceptable 
for subjects participating in the study.
In addition, if any of the following occur, further dosing will be withheld until the SRG reviews 
the relevant data, including unblinded data (if deemed necessary by the SRG request), and will 
decide whether it is safe to suspend dosing or continue dosing at either the planned or alternative 
dose levels or decides to prematurely terminate the study:
1. Two or more subjects in any single cohort or across more than 1 cohort experience the same 
type of serious or medically significant event as defined by the Investigator 
2. Two or more subjects in any single cohort or across more than 1 cohort experience alanine 
aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations >5 × upper limits
of normal (ULN) in the absence of a concomitant bilirubin increase (see point 3 below) 


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3. One or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN in the presence of a total bilirubin increase >2 ×ULN or an 
international normalized ratio (INR) >1.5 without findings of cholestasis or other alternate 
etiology to explain the elevations (i.e., “Hy’s Law cases”)
4. Two or more subjects in any single cohort or across more than 1 cohort experience ALT and/or 
AST elevations >3 ×ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
6.3.2 Criteria for Premature Termination or Suspension of Investigational 
Sites 
A study site may be terminated prematurely or suspended if the site (including the Investigator) is 
found in significant violation of Good Clinical Practice (GCP), protocol, or contractual agreement, 
is unable to ensure adequate study performance, or as otherwise permitted by the contractual 
agreement.
6.3.3 Procedures for Premature Termination or Suspension of the Study or the 
Participation of Investigational Site(s)
In the event that the sponsor, an IRB/independent ethics committee (IEC), or regulatory authority 
elects to terminate or suspend the study or the participation of an investigational site, a study-
specific procedure for early termination or suspension will be provided by the sponsor; applicable 
investigational sites will follow the procedure during the course of termination or study 
suspension. 
7.0 
SUBJECT POPULATION 
Screening for eligible subjects will be performed within 28 days prior to randomization or first 
dose.  
7.1 
Inclusion Criteria 
Subject eligibility is determined according to the following criteria prior to entry into the study:
1. In the Investigator's opinion, the subject can understand and sign the Informed Consent Form 
and comply with all protocol requirements.
2. The subject is a healthy male or female adult who is 18 to 55 years of age, inclusive at the time 
of ICF. 
3. Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 32.0 kg/m2, inclusive 
at Screening. 
4. A male subject who is nonsterilized* and sexually active with a female partner of childbearing 
potential* agree to use two forms of adequate contraception* from signing the ICF throughout 
the study and for 90 days after the last dose. 
*Definitions and acceptable methods of contraception are defined in 
Section 9.1.13 Contraception and Pregnancy Avoidance Procedure, and 
reporting responsibilities are defined in Section 9.1.14 Pregnancy. 


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5. A female subject of childbearing potential who complies with contraception requirements* or 
a female with no childbearing potential, defined as the subject has been surgically sterilized 
(hysterectomy, bilateral oophorectomy) or who are postmenopausal (defined as continuous 
amenorrhea of at least 2 years and FSH>40 IU/L).
Note: hormonal contraceptives are not permitted for female participants, as referenced in 
Table 3. Female partners of male participants can use hormonal contraceptives.
7.2
Exclusion Criteria
Any subject who meets any of the following criteria will not qualify for entry into the study: 
1. Subject has received any investigational compound within 30 days prior to the first dose of 
study medication or within 5 half-lives, whichever is greater. 
2. Subject is a study site employee or an immediate family member of a study site employee.  
3. Subject has evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic 
disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious 
allergy, full-body allergic skin rash (including hives), psychiatric disorder, evidence of 
abnormal liver function test, evidence of abnormal renal function tests or other abnormality 
that may impact the ability of the subject to participate or potentially confound the study 
results.  
Note: Healthy volunteers with pre-existing stable disease, defined as diseases not requiring 
significant change in therapy or hospitalization for worsening disease during the 6 wks before 
enrolment, may be included at the discretion of the Investigator. 
4. There is any finding in the subject’s medical history, physical examination, or safety laboratory 
tests giving reasonable suspicion of a disease that would contraindicate taking CVN766 or a 
similar drug in the same class or that might interfere with the conduct of the study 
5. Subject has a known hypersensitivity to any component of the formulation of CVN766. 
6. Subject has a positive urine result for drugs of abuse at Screening or Inpatient Check-in (Day -
1). 
7. Subject has a history of a major psychiatric illness or currently receiving therapy for a 
psychiatric condition 
8. Subject has a history of drug abuse or a history of alcohol abuse (more than 14 units/week) 
within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and 
drugs throughout the study. 
9. Subject has taken any excluded medication, supplements, or food products listed in the 
Excluded Medications and Dietary Products table as listed in Table 3. 


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10. Male subjects who do not agree to all the following rules: when sexually active with a female 
partner(s) of childbearing potential during the study, and for 90 days after the last dose of study 
drug: a) must use two acceptable methods of birth control (condom combined with highly 
effective method of contraception as listed in Section 9.1.13). Female partners of male 
participants can use hormonal contraception, and this should be in place for at least 30 days 
prior to dosing. Male subjects must also agree to refrain from sperm donation during the study 
and until 90 days after the last dose of the study drug.  
11. Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova 
during the study or 30 days after the last dose of the study drug. Women of childbearing 
potential must agree to practice an acceptable method of birth control (e.g., intrauterine device, 
barrier, abstinence).  
Note: hormonal contraceptives are not permitted for female participants, as referenced in Table 3. Female partners of 
male participants can use hormonal contraceptives. 
*Definitions and acceptable methods of contraception are defined in Section 9.1.13. Contraception and 
Pregnancy Avoidance Procedure and reporting responsibilities are defined in Section 9.1.14 Pregnancy. 
12. Subject has previously had a seizure or convulsion (lifetime, with the exception of febrile 
seizures), including absence seizure. 
13. Subject has current o recent (within 6 months) gastrointestinal disease that would be expected 
to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention 
known to impact absorption [e.g., bariatric surgery or bowel resection], esophageal reflux, 
peptic ulcer disease, erosive esophagitis, or frequent [i.e., more than once per week] occurrence 
of heartburn).
14. Subject has a history of cancer or other malignancy, except for basal cell carcinoma or 
squamous cell carcinoma that has been in remission for at least 3 years prior to Day 1.
15. Subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus 
(HCV) antibody, or a human immunodeficiency virus infection at Screening.
16. Subject who regularly use nicotine-containing products (including but not limited to cigarettes, 
electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum). The 
casual users (
10 cigarettes/week) may participate but must agree to refrain from the time of 
Screening for the duration of the study or a positive urine cotinine test at Inpatient Check-in 
(Day -1).
17. Subject has poor peripheral venous access (defined as more than three failed attempts to 
cannulate.
18. Subject has donated or lost 450 mL or more of their blood volume (including plasmapheresis)
or had a transfusion of any blood product within 45 days prior to Day 1.
19. Subject has an abnormal (CS) ECG at Screening or Inpatient Check-in (Day -1). Entry of any 
subject with an abnormal (NCS) ECG must be approved and documented by signature by the 
Investigator or medically qualified sub-Investigator. 


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20. Subject has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 
40 to 90 mm Hg for diastolic, confirmed with repeat per PI discretion at the Screening Visit or 
Inpatient Check-in (Day -1). 
21. Subject has a resting heart rate outside the range of 40 to 100 bpm, confirmed with repeat per 
PI discretion at the Screening Visit or Inpatient Check-in (Day -1). 
22. Subject has a QT interval with Fridericia’s correction method (QTcF) >450 ms (males) or 
>470 ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat testing 
at the Screening Visit or Inpatient Check-in (Day -1) Visit. 
23. Subject has abnormal Screening or Inpatient Check-in (Day -1) laboratory values that suggest 
a CS underlying disease or subject with the following lab abnormalities: ALT and/or AST >1.5 
the ULN, confirmed with one repeat testing. 
24. Subject has a risk of suicide according to the Investigator’s clinical judgment or has made a 
suicide attempt in the previous 2 years. 
7.3 
Excluded Medications and Dietary Products 
Use of the agents in Table 3 (prescription or nonprescription) is prohibited from the time points 
specified until completion of all study activities 
Table 3 
Prohibited Medications and Dietary Products 
28 days 
prior to  
Inpatient 
Check-in
14 days 
 prior to 
Inpatient 
Check-in
7 days 
prior to Inpatient 
Check-in 
72 hours 
prior to 
Inpatient 
Check-in 
48 hours 
prior to 
Inpatient 
Check-in
24 hours  
prior to 
Inpatient 
Check-in 
Nutraceuticals 
(e.g., St. John’s 
wort, ginseng, 
kava kava, 
ginkgo biloba, 
Chinese herbs, 
and melatonin) 
Prescription 
medications 
(d)(including 
hormonal 
contraceptives(e
)) 
OTC medications, 
including antacids, 
proton-pump 
inhibitors, and H2 
receptor antagonists (a)
Nicotine-
containing 
products
Alcohol-
containing 
products 
Products 
containing 
caffeine or 
xanthine 
(e.g., tea or 
coffee) 
Immunization/
Vaccines (b)
 
Vitamin supplements 
Poppy seeds
Known strong 
inhibitors/induc
ers of CYPs 
3A4/5 (c)
 
Orexin receptor 
antagonists including 
suvorexant 
(Belsomra®), 
lemborexant 
(Dayvigo®), and 
related compounds 


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CYP= cytochrome P-450, OTC=over the counter. 
(a) Occasional use of acetaminophen (~1 g/day) and 400mg ibuprofen TDS when required or other medication as 
approved by the sponsor’s Medical Monitor on a case-by-case basis is allowed except on Day 1 
(b)
Inclusive of but not limited to H1N1 and flu vaccinations. Subjects who have received the COVID-19 Vaccine 
between -10 and -28 days may participate, provided they did not experience any side effects of any description. 
COVID-19 vaccine doses may be administered 7 days post-study medication dosing.  
(c)
e.g., chloramphenicol, clarithromycin, ketoconazole.
(d)
Certain prescription medications may be allowed on a case-by-case basis at the discretion of the Investigator and 
Sponsor.  
(e)
Hormonal contraceptives are not permitted for female participants, as referenced in Table 3. Female partners of 
male participants can use hormonal contraceptives. 
Subjects must be instructed not to take any medications during study participation, including over-the-counter drug 
products, without first consulting with the Investigator. 
7.4
Diet, Fluid, Activity Control 
Subjects will be confined to the clinic for each of the dosing days as well as a period of time 
sufficient to collect additional post-dose PK samples and monitor for safety and tolerability (Day 
-1 through Day 4 for single-dose cohorts and Day-1 through Day 9 for multiple-dose cohorts). 
During confinement, subjects will be provided 3 standard meals and a snack per day, each 
containing approximately 30% fat (relative to the total calories). The meals served on the day of 
dosing should be similar in nutritional content for each subject in the study. The study menu should 
be recorded and submitted to the study file with a copy provided to the sponsor following 
treatment. Breakfast will not be provided on dosing days until at least 4 hours after dose 
administration unless otherwise indicated (i.e., Days 2-6 for MAD cohorts). The meal start and 
stop times, and percentage of the meal consumed will be recorded in the source, and the appropriate 
electronic case report form (eCRF) for all meals served on dosing days. 
If a blood draw or any study procedure coincides with a meal, the blood draw will take precedence,
followed by the study procedure and then the meal.
Subjects will remain in bed at a semi-supine position for 4 hours following the dose administration, 
except as necessitated by the occurrence of an AE or study procedures (e.g., obtaining a 12-lead 
ECG). Subjects must refrain from strenuous exercise for 72 hours before Inpatient Check-in and 
until check-out.
On the dosing days where extensive PK and/or CSF sampling is indicated (i.e., single-dosing Day 
1 and first and last multiple-dose days, e.g., days 1 and 7), CVN766 or placebo suspension will be 
administered with approximately 240 mL of water after a fast of at least 10 hours. Subjects will 
continue to fast for an additional 4 hours after dosing and eat lunch following the 4-hour PK blood 
and CSF collection. Subjects may consume water ad libitum except for 1 hour before and 1 hour 
after drug administration.


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For the food effect cohort (S3), single-dose administration will be administered after ingesting a 
standardized high-fat, high-calorie meal according to FDA Guidance for Industry (Food-effect 
bioavailability and fed bioequivalence studies, Dec 2002). Subjects will finish at least 
approximately 85% of their breakfast within 30 minutes and will receive an investigational product 
30 minutes (±5 minutes) after beginning the meal. The S3 (food effect) cohort meals may be 
staggered to ensure dosing occurs 30 minutes after the beginning of the meal. 
Subjects will also fast for at least 10 hours prior to safety laboratory collection times as indicated. 
However, consumption of water as desired is permitted during this time, except for dosing days, 
as indicated above. 
7.5 
Criteria for Discontinuation or Withdrawal of a Subject 
The primary reason for discontinuation or withdrawal of the subject from the study or study 
medication should be recorded in the eCRF using the following categories. For screen failure 
subjects, Section 9.1.15. 
1. The subject has experienced a PTE or AE that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health or the subject is unwilling 
to continue because of the PTE or AE. 
2. Liver Function Test (LFT) Abnormalities
Study medication should be discontinued immediately with appropriate clinical follow-up 
(including repeat laboratory tests until a subject’s laboratory profile has returned to 
normal/baseline status) if the following circumstances occur at any time during study 
medication treatment:
–
ALT or AST >8 × ULN, or
–
ALT or AST >5 × ULN and persists for more than 2 weeks, or
–
ALT or AST >3 × ULN in conjunction with elevated total bilirubin >2 × ULN or INR >1.5, 
or 
–
ALT or AST >3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%).
3. Significant protocol deviation. The discovery post-randomization that the subject failed to 
meet protocol entry criteria or did not adhere to protocol requirements and continued 
participation poses an unacceptable risk to the subject’s health.
4. Lost to follow-up. The subject did not return to the clinic, and attempts to contact the subject 
were unsuccessful. Attempts to reach the subject must be documented.
5. Voluntary withdrawal. The subject (or subject’s legally acceptable representative) wishes to 
withdraw from the study. The reason for withdrawal, if provided, should be recorded in the 
eCRF.


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Note: All attempts should be made to determine the underlying reason for the withdrawal, and, 
where possible, the primary underlying reason should be recorded (i.e., withdrawal due to an 
AE).
6. The sponsor, IRB, IEC, or regulatory agency terminates the study.
7. Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF.
7.6
Procedures for Discontinuation or Withdrawal of a Subject 
The Investigator must discontinue a subject’s study participation at any time during the study when 
the subject meets the study discontinuation criteria described in Section 7.5. In addition, a subject 
may discontinue their participation without giving a reason at any time during the study. Should a 
subject’s involvement be terminated, the primary criterion for termination must be recorded by the 
Investigator. In addition, efforts should be made to perform all procedures scheduled for the Early 
Termination Visit. Discontinued or withdrawn subjects may be replaced at the  Sponsor’s 
discretion. 
Participants who withdraw from the study prior to dosing may be replaced. If a participant 
withdraws after the first dose of study medication or placebo, no replacement will occur.
8.0 
CLINICAL TRIAL MANAGEMENT
8.1 
Study Medication and Materials 
This section contains information regarding all medication and materials provided directly by the 
sponsor and/or sourced by other means required by the study protocol, including important 
sections describing the management of clinical trial material. 
8.1.1
Dosage Form, Manufacturing, Packaging, and Labeling
Study drug refers to CVN766 and matching placebo. Study drug will be provided in bulk supply. 
An unblinded pharmacist will manage and prepare doses as oral suspensions as needed throughout 
the study. 
In this protocol, the term study medication refers to all or any of the drugs defined below.
8.1.1.1
Investigational Drug
CVN766 and Matching Placebo 


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CVN766 drug substance is supplied as a bulk powder to the clinical site and then compounded 
into oral suspensions. A matching placebo suspension containing all of the components of the 
active oral suspension with the exception of the drug substance will also be compounded by the 
site. Compounding instructions will be outlined in a separate pharmacy manual and provided by 
the sponsor. See Table 4 for the composition of the drug product and matching placebo 
suspensions.  
The oral suspensions will be labeled with the appropriate study information and caution 
statements.  
Table 4 
Composition of CVN766 Oral Suspension and Matching Placebo 
Component 
 
CVN766 Oral Suspension (individual dose) 
Matching 
Placebo 
CVN766 drug substance 
5 mg 
15 mg 
45 mg 
125 mg 
250 mg 
NA 
 Commercial suspending 
vehiclea
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
10.0 mL 
NA=Not applicable 
a An off-the-shelf commercial suspending vehicle will be used, and the details of the vehicle will be provided in the 
Pharmacy Manual. 
8.1.1.2 Ancillary Materials  
Ancillary materials will be provided by either the clinical site and/or the sponsor based on 
availability.  
Ancillary material details are provided in the pharmacy manual. 
Unused ancillary materials, if provided by the sponsor, will be accounted for and disposed of as 
directed by the sponsor or their designee. 
 
 
8.1.2
Drug Storage
All clinical trial material must be kept in an appropriate, limited-access, secure place until used 
or returned to the sponsor or designee for destruction. 
All study medication must be stored under the conditions specified on the label and remain in the 
original container until dispensed. A daily temperature log of the drug storage area must be 
maintained every working day.
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CVN766 drug substance is stored at room temperature. CVN766 oral suspension and matching 
placebo should be stored according to instructions in the Pharmacy Manual.  
8.1.3 Dose and Regimen 
The Investigator or Investigator’s designee will instruct the subject on dosing procedures.
All dosing will occur while subjects are in the clinic under the supervision of the Investigator and 
in fed or fasting conditions as outlined in Section 7.4. 
The exact time of dose will be recorded in the source documents and on the appropriate eCRF. 
The planned dose levels to be studied are provided in Table 5. If the planned highest dose level 
does not reach the desired exposure, then additional cohorts with higher dose levels may be 
considered. If all planned dose levels are not tolerated in an earlier cohort, the following cohorts 
may study lower doses at the discretion of the Investigator and the SRG. The actual choice of the 
subsequent dose level will occur after a full review of the available blinded safety, tolerability, and 
clinical laboratory results, and available PK data in the preceding cohort. The subsequent dose 
level may be higher, lower, or remain the same as the preceding dose level. 
Table 5 describes the treatment and medication type that would be provided for each cohort.
Table 5
Planned Single and Multiple Dose Levels by Cohort 
Single-Dose Cohorts
Cohort
Planned Treatment* 
No. of Subjects 
Medication Type
S1  
CVN766 5 mg
6
oral suspension
Placebo 
2
oral suspension 
S2 
CVN766 15 mg
6
oral suspension 
Placebo
2
oral suspension
S3 Fasted
CVN766 45 mg
6
oral suspension 
Placebo
2
oral suspension
S3 Fed (Same 8 subjects as 
in the S3 FASTED cohort)
CVN766 45 mg
6
oral suspension 
 
Placebo 
2
oral suspension 
S4 
CVN766 125 mg
6
oral suspension 
Placebo 
2
oral suspension 
S5 
CVN766 250 mg
6
oral suspension 
Placebo 
2
oral suspension 
 


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Multiple Dose Cohorts 
Cohort
Planned Treatment*
No. of Subjects 
Medication Type
M1 
CVN766 45 mg
6
oral suspension
Placebo
2
oral suspension 
M2 
CVN766 125 mg
6
oral suspension
Placebo
2
oral suspension 
M3 
CVN766 250 mg
6
oral suspension 
Placebo
2
oral suspension
* Dose (active or placebo) is in 10 mL of suspension. 
8.1.4 Overdose 
An overdose is defined as a known, deliberate, or accidental administration of an investigational 
drug, to or by a study subject, at a dose above that assigned to that individual subject according to 
the study protocol.
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF, in order to capture this important safety information consistently in the database. 
Cases of overdose without manifested signs or symptoms are not considered AEs. AEs associated 
with an overdose will be documented on AE eCRF(s) according to Section 9.7.2, PTEs and AEs.
Serious adverse events (SAEs) associated with an overdose should be reported according to the 
procedure outlined in Section 9.7.4, Collection and Reporting of SAEs.
In the event of an overdose, supportive measures should be employed as needed, e.g.,
administration of supportive therapy as dictated by the subject’s clinical status, removal of 
unabsorbed material from the gastrointestinal tract, or the initiation of additional clinical 
monitoring.  
8.2
Investigational Drug Assignment and Dispensing Procedures
Subjects will be assigned to receive a unique randomization number.
The clinical site will use the unique identifier to facilitate the pre-labeling of PK samples. It should 
also be contained on the PK transport vials shipped to the bioanalytical laboratory and will be used 
by the laboratory to report the subject data results. This unique identifier should only be used for 
the purposes described in this section. This identifier will be assigned upon randomization in the 
order in which subjects receive their first dose of the study drug. 
8.3
Randomization Code Creation and Storage 
The sponsor or their designee will generate the randomization schedule and provide a copy to the 
site pharmacist and bioanalytical laboratory prior to the start of the study. All randomization 
information will be stored in a secured area, accessible only by authorized personnel. 


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8.4
Investigational Drug Blind Maintenance
The investigational drug blind is maintained through a randomization schedule held by the 
dispensing pharmacist.
8.5
Unblinding Procedure
The investigational drug blind shall not be broken by the investigative staff unless information 
concerning the investigational drug is necessary for the medical treatment of the subject. All study 
assessments and causality assessments should be performed, if possible, prior to unblinding. In the 
event of a medical emergency, if possible, the medical monitor should be contacted to discuss the 
need for unblinding before the investigational drug blind is broken. 
Unblinding envelopes will be supplied to the site prior to the first subject dosing and stored in a 
central and secure place to ensure access in the event of an emergency.  Study staff will be trained 
on unblinding procedures. 
The sponsor must be notified as soon as possible if the investigational drug blind is broken. The 
date, time, and reason the blind is broken must be recorded in the source documents, and the same 
information (except the time) must be recorded on the eCRF. 
If any site personnel inadvertently become unblinded, the sponsor must be notified, and the SRG 
will determine whether to discontinue dosing or withdraw from the study of all affected subjects. 
No change should be made to any assessment of the subject after unblinding. 
Following assessment of the AE data and pre-defined criteria for study termination, dose escalation 
may be interrupted/stopped and the blind broken for further analysis. Based on a review of 
unblinded data, the sponsor, in consultation with the Investigator, will decide if and how it is 
appropriate for the study to proceed.
The Randomization schedule for all subjects will be released for analysis after the database for 
these cohorts is locked. The Investigator will be unblinded after database lock for all the cohorts 
if necessary. 
8.6 
Accountability and Destruction of Sponsor-Supplied Drugs 
Drug supplies will be counted and reconciled at the site before being returned to the sponsor or 
designee or being destroyed.  
The Investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to subjects enrolled in the study. To document the 
appropriate use of study medication, the Investigator must maintain records of all study medication 
delivery to the site, site inventory used by each subject, and return to the sponsor or designee. 


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Upon receipt of study medication, the Investigator or designee must verify the contents of the 
shipments against the packing list, ensure the quantity is correct, and the medication is received 
within the labeled storage conditions. If quantity and conditions are acceptable, the Investigator or 
designee should acknowledge the receipt of the shipment by signing the bottom half of the packing 
list and send via email and per instructions provided on the form. If any discrepancies exist 
between the packing list and the actual product received, the sponsor must be contacted to resolve 
the issue. The packing list should be filed in the Investigator’s essential document file. The 
Investigator must maintain 100% accountability for all study medication received and dispensed 
during their entire participation in the study. Proper drug accountability includes, but is not limited 
to: 
 Continuously monitoring expiration dates 
 Frequently verifying that actual inventory matches documented inventory 
 Verifying that the log is completed for the drug lot used to prepare each dose 
 Verifying that all containers used are documented accurately on the log 
 Verifying that required fields are completed accurately and legibly 
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
The Investigator or designee must record the current inventory of all study medication on a 
sponsor-approved drug accountability log. The following information will be recorded at a 
minimum: protocol number and title, name of the Investigator, site identifier and number, 
description of study medication, expiry date, and amount dispensed, including the initials of the 
person dispensing and receiving the study medication. The log should include all required 
information as a separate entry for each subject to whom study medication is dispensed. 
Prior to site closure or at appropriate intervals, a representative from the sponsor or its designee 
will perform clinical study material accountability and reconciliation before clinical study 
materials are returned to the sponsor or its designee for destruction or destroyed at the site, as 
applicable. The Investigator will retain the original documentation regarding clinical study 
material accountability, return, and/or destruction, and copies will be sent to the sponsor or 
designee. 
The Investigator will be notified of any expiry date or retest date extension of clinical study 
material during the study conduct. On expiry date notification from the sponsor or designee, the 
site must complete all instructions outlined in the notification, including segregation of expired 
clinical study material for return to the sponsor or its designee for destruction. 
 


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9.0
STUDY PLAN
9.1
Study Procedures 
The following sections describe the study procedures and data to be collected. For each procedure, 
subjects are to be assessed by the same Investigator or site personnel whenever possible. The 
Schedule of Study Procedures is located in Appendix A.
9.1.1
Informed Consent Procedure 
The requirements of the ICF are described in Section 14.2.
The ICF must be obtained prior to the subject entering the study and before any protocol-related 
procedures are performed.
A unique subject screening number (of the form xx-xxx), the first two numbers for the site, 
subsequent three numbers for subject identification will be assigned to each subject when the ICF 
is obtained. This subject ID will be used until the subject is assigned their 4-digit randomization 
number. 
9.1.1.1 Pharmacogenomic and Cerebrospinal Fluid Informed Consent Procedure 
Pharmacogenomics and cerebrospinal fluid informed consent is a component of the overall study 
ICF. The requirements are described in Section 14.2. 
The pharmacogenomic and (for applicable cohorts) cerebrospinal fluid sample collection is 
mandatory. 
9.1.2 Demographics, Medical History, and Medication History Procedure 
Demographic information to be obtained will include date of birth, sex, ethnicity, race as described 
by the subject, smoking status, and caffeine consumption at Screening.
Medical history to be obtained will include determining whether the subject has any significant 
conditions or diseases that stopped at or prior to signing the ICF. Ongoing conditions are 
considered concurrent medical conditions (see Section 9.1.7).
Medication history information to be obtained includes any medication relevant to eligibility 
criteria stopped at or within 28 days before signing ICF.


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9.1.3
Physical Examination Procedure
A physical examination performed by the Investigator or medical officer consists of the following 
body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; 
(5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; 
(9) nervous system; (10) lymph nodes; and (11) other.  
Any abnormal change from the baseline physical examination (Screening and Inpatient Check-in 
[Day -1]) must be assessed as not CS or CS by the Investigator and recorded in the source 
document and eCRF.  
All CS findings/changes, as determined by the Investigator, from the baseline physical 
examination will be recorded as a PTE or concurrent medical condition in the source document 
and on the appropriate eCRF described in Section 9.8.1 or Section 9.8.2.  
On subsequent examinations, any abnormal change from the pretreatment physical examination 
assessment occurring immediately prior to the investigational drug Inpatient Check-in (Day -1) 
must be assessed as not clinically significant (NCS) or CS by the Investigator and recorded in the 
source document and eCRF. Any CS change or new diagnosis as a result of a CS change, as 
determined by the Investigator, will be recorded as an AE in source documentation and on the 
PTE/AE eCRF. 
9.1.4 Weight, Height, and BMI 
A subject should have weight and height measured while wearing indoor clothing and with shoes 
off. The BMI is calculated using metric units with the formula provided below:  
Height is recorded centimeters without decimal places, and for weight, it is kilograms (kg) with 1 
decimal place. BMI should be derived as: 
Metric:  
BMI = weight (kg)/[height (m)]2
Results for BMI will be expressed with 1 decimal place.
Example:
Height=176 cm (or 1.76 m), weight=79.2 kg; BMI=79.2/1.762=25.57 kg/m2 captured as 
25.6 kg/m2.  
 


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9.1.5
Vital Sign Procedure
Vital signs will include tympanic body temperature, respiration, pulse, and blood pressure and be 
collected at timepoints specified in the Schedule of Study Procedures (Appendix A). For eligibility 
determination, the pulse will not be derived from ECG. Pulse and blood pressure will be measured 
after at least 5 minutes supine and again after 2 minutes standing.  
Vital signs should be measured at the same time (+/- 1 hour) of the day across visits if possible. 
When vital signs are scheduled at the same time as blood draws, the blood draw will take priority,
and vital signs will be obtained within approximately 0.25 hours before or after the scheduled 
blood draw.
9.1.6 Documentation of Concomitant Medications
Concomitant medication is any drug given in addition to the study medication. These may be 
prescribed by a physician or obtained by the subject over the counter. Concomitant medication is 
not provided by the sponsor. At each study visit, subjects will be asked whether they have taken 
any medication other than the study medication (used from the signing of ICF through the end of 
the study), and all medication, including vitamin supplements, over-the-counter medications, and 
oral herbal preparations, must be recorded in the eCRF. Documentation will include generic 
medication name, dose, unit, frequency, route of administration, start and end dates, and reason 
for use. 
9.1.7 Documentation of Concurrent Medical Conditions 
Concurrent medical conditions are those significant ongoing conditions or diseases that are present 
at the signing of ICF. This includes CS laboratory, ECG, or physical examination abnormalities 
noted at Screening examination. The condition (i.e., diagnosis) should be described. 
9.1.8 ECG Procedure 
Standard 12-lead ECGs will be recorded at timepoints specified in the Schedule of Study 
Procedures (Appendix A). Triplicate ECGs will be taken at least 1-minute apart at each scheduled 
time. The average of the ECG measurements will be used for determining eligibility. Additional 
unscheduled ECGs may be recorded where clinically necessary for subject safety.
When an ECG is scheduled at the same time as blood draws or vital signs, then the blood draws 
and vital signs will take priority, and the ECG will be obtained within 0.5 hour before or after the 
scheduled blood draw/vital sign assessment. If an ECG coincides with a meal, ECG will take 
precedence, followed by the meal. 
All stationary 12-lead ECG machines will be supplied by the site. Subjects should be in a supine 
position following an approximate 10-minute rest period for ECG recordings. Should technical 
difficulties occur during the recording of the ECG, a reasonable attempt should be made to repeat 
the ECG shortly after the failed attempt. 


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ECGs will be read automatically, and also, the Investigator or sub-Investigator will manually 
interpret the ECG using 1 of the following categories: within normal limits, abnormal but not CS, 
or abnormal and CS. Abnormal QTc readings will be manually recalculated and reported by the 
Investigator on the eCRF. All 12-lead ECGs will be stored for manual measurement of intervals, 
if necessary. Twelve-lead ECGs will be recorded using an ECG machine that automatically 
calculates the heart rate and measures PR interval, RR interval, QRS interval, QT interval, and 
QTcF and QTcB (Fridericia’s and Bazett’s correction) intervals. Paper ECG traces will be 
recorded for 10 seconds at a standard paper speed of 25 mm/sec, and gain of 10 m/mV or digital 
recordings will be used.  
One copy of the 12-lead ECG with the physician’s signature and date of assessment will be filed 
with the source documents and captured in the appropriate eCRF. If the original ECG is printed 
on thermal paper, the ECG report must be photocopied and certified. The photocopy will be filed 
with the original ECG in the source. 
All ECGs will be recorded at the time points detailed in Appendix A.
9.1.9 Pharmacogenomic Sample Collection 
Every subject must sign ICF/be consented to the sampling of whole blood for pharmacogenomic 
analysis to participate in the study. 
One whole blood sample for DNA isolation and genotyping will be collected at time points 
specified in the Schedule of Study Procedures (Appendix A) into plastic dipotassium 
ethylenediamine-tetra acetic acid (K2EDTA) spray-coated tubes and stored under frozen 
conditions. In addition, two whole blood samples will be collected at time points specified in the 
Schedule of Study Procedures (Appendix A) for ribonucleic acid (RNA) pharmacogenomic 
analysis. The pre-dose RNA blood samples should be collected under fasted conditions and prior 
to any other blood collection. 
DNA may be evaluated for the genetic contribution to how the drug is broken down or affects the 
body. This is called a “pharmacogenomics research study.” Specific purposes of this study include:
Identifying genetic reasons why certain people respond differently to CVN766
Finding out more information about how CVN766 works
Generating information needed for research, development, and regulatory approval of tests to 
predict response to CVN766
Identifying variations in genes related to the biological target of CVN766
This information may be used, for example, to develop a better understanding of the safety and 
efficacy of CVN766 and other study medications and for improving the efficiency, design, and 
study methods of future research studies.


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The samples will be stored no longer than 15 years after completion of the CVN766 study and/or 
until the drug development of CVN766 is no longer actively pursued by the sponsor or its 
collaborators. No samples will be stored for longer than permitted by the applicable law, and 
samples will be destroyed upon notification from the sponsor. “Stored samples” in this context are 
defined as samples that are double coded (the samples are stripped of all personal identifying 
information but a key links the samples to the clinical data collected from the sample donor) and 
are used in the analysis of investigational drug or related drug. 
The sampling of whole blood for pharmacogenomic and genotyping analysis is mandatory; every 
subject must sign the ICF in order to participate in this study. DNA samples will be collected and 
may be used to evaluate drug metabolic enzyme and transporter polymorphisms that may 
contribute to the variability in the PK of CVN766. Also, since pharmacogenomics is an evolving 
science, many genes and their functions are not yet fully understood. Future data may suggest a 
role of some of these genes in drug response, which may lead to additional hypothesis-generating 
exploratory research and diagnostic development on stored samples. 
If necessary and feasible, a second aliquot of blood may be taken if isolation of DNA and RNA 
from the first sample was not successful or possible. 
Samples will be frozen at -70°C or lower and shipped separately on dry ice prior to extraction and 
storage at -70°C or lower. Samples should not be allowed to thaw until processed. 
Detailed instructions for the handling and shipping of samples are provided in a separate lab 
manual. 
Genotyping on collected samples may be deferred until after the completion of the study’s in-life 
activities. 
Each pharmacogenomic sample for a study subject should be identifiable on the requisition form 
with the 4-digit randomization number.
9.1.10 PK Sample Collection
9.1.10.1 Collection of Blood for PK Sampling 
Blood samples for analysis of CVN766 plasma concentrations will be collected into chilled 
Vacutainers containing K2EDTA according to the schedule in Appendix A. Instructions for 
sample processing and shipment are provided in a separate lab manual.
In all single-dose cohorts, serial blood samples to determine CVN766 concentrations in plasma 
will be collected according to Table 6. 
Table 6 
Collection of Blood Samples for PK Analysis in Single-Dose Cohorts 


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Sample 
Type 
Dosing 
Day 
Time Post-dose (hours). 
Plasma
1
Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24-, 
36-, 48-, and 72-hours post-dose.  
In all cohorts for Part 2, serial blood samples for determination of CVN766 concentrations in 
plasma will be collected according to Table 7.
Table 7
Collection of Blood Samples for PK Analysis in Multiple-Dose Cohorts 
Sample Type
Dosing Day
Time Post-dose (hours).
Plasma
1
Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 
12, 16, and 24 (Day 2 pre-dose) hours post-dose. 
 
3,4,5,6 
Pre-dose (within 15 minutes prior to dosing) 
 
7
Pre-dose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 
12, 16, 24, 36, 48, and 72 (a) hours post-dose.  
(a) If emerging PK data indicate the CVN766 t½ is 15 hours (or less), the 72-hour timepoint is unnecessary.
The PK samples will be collected at the nominal time point; all other assessments will be collected, 
before or after, within the allowable windows. The actual time of sample collection will be 
recorded on the source document and eCRF. 
Sampling time points may be adjusted or added based on the preliminary emerging PK data 
collected from prior cohort(s). Still, the total number of samples collected per subject should not 
exceed the planned number by more than 4.
Placebo samples will not be analyzed by the bioanalytical laboratory except 2 samples per subject 
receiving placebo, 1 pre-dose, and the other around the expected time at which Cmax occurred (as 
emerging from the actual measurement of the samples of the first dose group) to ensure from a 
safety perspective that no additional subjects could have been on active treatment.
 
 
 
 
 
 
 
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9.1.11 PK Parameters 
PK parameters of CVN766 will be derived using non-compartmental analysis methods from the 
concentration-time data for all evaluable subjects. Actual sampling times, rather than scheduled 
sampling times, will be used in all computations involving sampling times. The following PK 
parameters will be determined from concentrations of CVN766 in plasma and CSF:  
PPD


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Symbol/Term
Definition
Plasma
AUCt
Area under the plasma concentration-time curve from the time of dosing to the time of the 
last measurable concentration 
AUC
Area under the plasma concentration-time curve from time 0 to infinity, calculated as 
AUC =AUCt+Clast
z, where Clast is the last quantifiable concentration. 
AUC24
Area under the plasma concentration-time curve from time 0 to 24 hours, calculated using 
the linear trapezoidal rule.
AUC  
Area under the plasma concentration-time curve over the dosing interval ( ) 
Cmax 
Maximum observed plasma concentration.
Cmin 
Minimum observed plasma concentration; pre-dose trough concentration 
Minimum observed plasma concentration at steady state, on last day of dosing 
CL/F
Apparent clearance after extravascular administration, calculated as Dose/AUC after a 
single dose.
CL/Fss 
Apparent clearance after extravascular administration at steady state, calculated as 
Dose/AUCtau 
z
Terminal elimination rate constant, calculated as the negative of the slope of the log-linear 
regression of the natural logarithm concentration-time curve during the terminal phase 
t1/2z
Terminal elimination half-
z. 
tmax
Time to reach Cmax.
Vz/F 
Apparent volume of distribution during the terminal phase after extravascular 
z. 
Vz/Fss 
Apparent volume of distribution during the terminal phase after extravascular 
administration at a steady-state, calculated as (CL/Fss)/
z 
CSF
plasma: CSF ratio
ratio of the drug concentration in plasma vs. CSF
Additional PK parameters may be calculated as appropriate. 
 
9.1.12 Procedures for Clinical Laboratory Samples
All samples will be collected in accordance with acceptable laboratory procedures on the 
days/times stipulated in the Schedule of Study Procedures (Appendix A).
Table 10 lists the tests that will be obtained for each laboratory specimen.


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Table 10
Clinical Laboratory Tests
Hematology
Serum Chemistry
Urinalysis
RBC
WBC with differential  
     (% and absolute) 
Hemoglobin 
Hematocrit 
Platelets 
PT/INR 
ALT
Albumin 
Alkaline phosphatase 
Lipase (d) 
AST 
Total bilirubin 
Direct bilirubin 
Total protein 
Creatinine 
BUN/Urea 
Creatine kinase 
GGT 
Potassium 
Sodium 
Glucose 
Chloride 
Bicarbonate 
Calcium 
pH
Specific gravity 
Protein 
Glucose 
Blood  
Nitrite 
Microscopic Analysis
(only if positive dipstick results):  
RBC/high power field 
WBC/high power field 
Epithelial cells, casts etc.
Diagnostic Screening: 
Serum 
Urine/ Blood 
Serum hCG (a) 
FSH (b)  
Hepatitis panel, including HBsAg and anti-HCV (e) 
Human Immunodeficiency Virus (HIV) antibody
Drug screen including amphetamines (AMP), 
barbiturates (BAR), benzodiazepines (BZO), 
cannabinoids, cocaine (COC), opiates (OPI), 
alcohol, cotinine c methamphetamines, 
methadone (MET), 
methylenedioxymethamphetamine (MDMA), 
phencyclidine (PCP), tetrahydrocannabinol 
(THC) 
Urine Pregnancy Test (a)
Alcohol (can be performed via breath test) 
FT4= free T4, FSH= follicle-stimulating hormone, GGT= -glutamyl transferase, hCG= human chorionic 
gonadotropin, PT=prothrombin time, RBC=red blood cells, TSH= thyrotropin, WBC=white blood cells. 
(a) Serum hCG pregnancy test will be done at Screening,  Urine Pregnancy Test will be done at Check-in (Day -1).  
(b) FSH level will be obtained for female subjects at Screening if they are postmenopausal (i.e., last regular 
menstrual cycle >2 years) and not surgically sterile. The result must be >40 IU/L for the subject to be enrolled. 
(c) To be performed at Inpatient Check-in (Day -1). 
(d) To be performed on SAD Day -1 and 24- and 48-hours post-dose; and MAD fasting lipase tests will be 
performed on Day -1, Days 2,7 and 8 (predose).  
The local laboratory will perform all clinical laboratory tests. The results of laboratory tests will 
be returned to the Investigator, who is responsible for reviewing and filing these results. All 
laboratory safety data will be transferred electronically to the sponsor or designee in the format 
requested by the sponsor. The Investigator will maintain a copy of the laboratory accreditation and 
the reference ranges for the laboratory used.  


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Laboratory reports must be signed and dated by the Investigator or sub-Investigator, indicating 
that the report has been reviewed and any abnormalities have been assessed for clinical 
significance. Subjects will be referred to their primary care physician for follow-up of any 
clinically significant findings or where the Investigator or medically trained sub-Investigator
deems appropriate. 
All CS laboratory abnormalities must be recorded as a PTE/AE in the subject’s source documents 
and on the appropriate eCRF. A CS laboratory abnormality that has been verified by retesting will 
be followed until the abnormality returns to an acceptable level or a satisfactory explanation has 
been obtained.
If subjects experience ALT or AST >3 ×ULN, follow-up laboratory tests at a minimum, serum 
alkaline phosphatase, ALT, AST, total bilirubin, GGT, and INR should be performed within a 
maximum of 7 days and preferably within 48 to 72 hours after the abnormality was found. 
(Please refer to Section 7.5 for discontinuation criteria and Section 9.8.3 for the appropriate 
guidance on Reporting of Abnormal LFT in relation to ALT or AST >3 ×ULN in conjunction with 
total bilirubin >2 ×ULN). 
If the ALT or AST remains elevated >3 ×ULN on these 2 consecutive occasions, the Investigator
must contact the Medical Monitor for consideration of additional testing, close monitoring, 
possible discontinuation of study medication, and discussion of the relevant subject details, and 
possible alternative etiologies. The abnormality should be recorded as an AE (please refer to 
Section 9.8.3 Reporting of Abnormal LFT for reporting requirements).
9.1.13 Contraception and Pregnancy Avoidance Procedure 
From the date of signing of ICF, throughout the duration of the study, and for 30 days after the last 
dose of study medication, females of childbearing potential* must use two acceptable methods of 
contraception and must agree not to donate eggs; Nonsterilized** male subjects who are sexually 
active with a female partner of childbearing potential* must use two acceptable method(s) of 
contraception throughout the duration of the study, and for 90 days after the last dose of study 
medication. In addition, males must be advised not to donate sperm for 90 days after the last dose 
of study medication. 
Females of childbearing potential are defined as any female who has experienced menarche and 
who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not 
postmenopausal.  
Menopause is defined as at least 2 years since the last regular menses with an FSH>40 IU/L or at 
least 5 years since the last regular menses, confirmed before any study medication is implemented.
Male subjects with potentially postmenopausal partners who are under the age of 55 years must 
use condoms unless their partner’s postmenopausal status has been confirmed by FSH level.  


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**Sterilized males should be at least 90 days post-vasectomy and confirm that they have obtained 
documentation of the absence of sperm in the ejaculate.
Acceptable and highly effective methods of contraception are:
Note: hormonal contraceptives are not permitted for female participants, as referenced in 
Table 3. Female partners of male participants can use hormonal contraceptives. 
• 
Nonhormonal intrauterine device (IUD) 
• 
Bilateral tubal occlusion 
• 
Vasectomised subject/partner with documented azoospermia 90 days after the 
procedure, if that partner is the sole sexual partner 
• 
Same-sex intercourse, if used consistently for the duration of the study and post-dosing 
as specified above  
Complete abstinence, defined as the complete avoidance of heterosexual intercourse - is an 
acceptable form of contraception if used consistently throughout the study and for the durations 
after dosing specified for males and females above. It is not necessary to use any other method of 
contraception when complete abstinence is elected. Females of childbearing potential who choose 
complete abstinence must continue to have pregnancy tests as per protocol. The reliability of 
sexual abstinence needs to be evaluated by the Investigator in relation to the duration of the clinical 
trial and the preferred and usual lifestyle of the subject. 
Subjects will be provided with information on acceptable methods of contraception as part of the 
subject's informed consent process and will be asked to sign an ICF stating that they understand 
the requirements for avoidance of pregnancy, egg donation, and sperm donation during the study. 
9.1.14 Pregnancy 
Women who are pregnant or breastfeeding will not be included in this study. 
If any subject is found to be pregnant during the study, she should be withdrawn, and any sponsor-
supplied drug should be immediately discontinued. In addition, any pregnancies in the partner of 
a male subject during the study or for 90 days after the last dose should also be recorded following 
authorization from the subject’s partner. 
If the pregnancy occurs during administration of active study medication, e.g., after Visit 1 or 
within 30 days of the last dose of active study medication, the pregnancy should be reported 
immediately, using a pregnancy notification form, to the contact listed in Section 1.0. 
Should the pregnancy occur during or after administration of the blinded drug, the Investigator
must inform the subject of their right to receive treatment information. If the subject chooses to 
receive unblinded treatment information, the individual blind should be broken by the Investigator. 
Subjects randomized to placebo need not be followed. 


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If the female subject and/or female partner of a male subject agrees to the primary care physician 
being informed, the Investigator should notify the primary care physician that the subject/female 
partner of the subject was participating in a clinical study at the time she became pregnant and 
provide details of treatment the subject received (blinded or unblinded, as applicable).
All reported pregnancies will be followed up to the final outcome using the pregnancy form. The 
outcome, including any premature termination, must be reported to the sponsor. An evaluation 
after the birth of the child will also be conducted for 8 weeks.
9.1.15 Documentation of Screen Failure 
Investigators must account for all subjects who sign ICF. If the subject is not eligible at this visit, 
the Investigator should complete the eCRF screen failure form. 
The primary reason for screen failure is recorded in the eCRF using the following categories:
 PTE/AE 
 Did not meet inclusion criteria or did meet exclusion criteria
 Significant protocol deviation 
 Lost to follow-up
 Voluntary withdrawal
 Study termination 
 Other 
Subject numbers assigned to subjects who fail screening should not be reused.  
If a subject fails screening, but is later successfully rescreened, the data for the subject will be 
entered as if these were two separate subjects. Therefore, the data should be entered as follows:
1. The screen failure data should be entered as a screen failure subject. 
2. Rescreened subjects should be assigned a new subject number and treated as a stand-alone 
subject. 
9.1.16 Documentation of Randomization
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria are eligible 
for randomization into the treatment phase. 
If the subject is not eligible for randomization, the Investigator should record the primary reason 
for failure on the applicable eCRF. 
 
 


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9.2
Monitoring Subject Treatment Compliance
Study medication will be administered while subjects are under observation in the clinical research 
unit. Following administration of the study medication, appropriate mouth and/or hand checks will 
be performed to ensure that the dose is swallowed and noted in the source document. The date and 
time of each dose will be recorded in the source documents and on the eCRFs. An inventory of the 
study medication supplies dispensed will be performed by the site pharmacist or authorized study 
designee and recorded onto the Drug Accountability Log in the subject’s source document records 
or equivalent. The exact dose time of consecutive subjects may be staggered to facilitate logistics 
at the site. 
9.3
Schedule of Observations and Procedures
The study-related procedures schedule for all evaluations is shown in Appendix A and is not 
duplicated in the following sections. 
9.3.1 Screening 
Subjects will be screened within 28 days prior to randomization. Subjects will be screened in 
accordance with predefined inclusion and exclusion criteria as described in Section 7.0. See 
Section 9.1.15 for procedures for documenting screening failures. Subjects who are screening 
failures may be screened a second time if their reason for failing screening is thought to be 
resolved. Rescreened subjects will receive a new Screening number. 
9.3.2 Inpatient Check-In 
All subjects will be admitted to the study clinic the day prior to randomization and first dose.  
Subjects participating in the food effect cohorts will also check into the study clinic the day prior 
to the scheduled dosing. 
9.3.3 Final Visit (discharge day from clinic) 
Subjects will be confined to the study clinic for the duration of the treatment period to permit 
supervised dosing of study drug and repeat study assessments.  Subjects participating in the single-
dose study and food effect assessment will be discharged no sooner than 72 hours post-dose, and 
subjects participating in the multiple-dose study will be discharged no sooner than 48 hours 
following their last dose.   
For all subjects receiving study medication, the Investigator must complete the End of Study eCRF 
page.
 


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9.3.4
Early Termination
Subjects who discontinue dosing or decide to check out of the study clinic early will be advised to 
allow the Investigator (or authorized designees) to complete early termination assessments for 
safety purposes prior to discharge. The reason for discontinuation must be documented in the 
source document and eCRF.  
For all subjects receiving study medication, the Investigator must complete the End of Study eCRF 
page. 
9.3.5 Follow-up Visit  
The Follow-up Visit will occur by telephone approximately 14 days (±2) after the final dose of 
study drug for the SAD cohorts and MAD cohorts unless abnormal CS findings were observed 
upon discharge or the SRG has determined additional PK sampling timepoints are indicated. In 
these cases, subjects must then be brought back to the clinic for re-evaluation per the Investigator’s 
discretion.  
9.4 
Biological Sample Retention and Destruction  
In all cohorts except S3 (fed), blood serum will be obtained on Day -1 and Day 2, and the collected 
serum will be stored at -70C to enable additional retrospective analyses as needed. Samples will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. 
Blood specimens for genome/gene analysis will be collected as described in Section 9.1.9, 
Pharmacogenomic Sample Collection. After extraction and purification, the genetic material will 
be preserved and retained at a biorepository selected by the sponsor for up to but not longer than 
15 years or as required by applicable law. Blood and urine samples for PK analysis will be 
collected as described in Section 9.1.10, PK Sample Collection.  Once PK analysis is complete, 
backup plasma and urine samples will be preserved and retained at a biorepository selected by the 
sponsor for up to, but not longer than, 15 years or as required by applicable law, to enable the 
conduct of exploratory, qualitative, metabolite identification studies or measurement of target 
related biomarkers, should the sponsor decide these are informative. The sponsor has put a system 
to protect the subjects’ personal information to ensure optimal confidentiality and defined standard 
processes for sample and data collection, storage, analysis, and destruction. 
The sample will be labeled with a unique sample identifier similar to labeling in the main study 
but using a code different from the code attached to the health information and other clinical test 
results collected in the study. The sample and data are linked to personal health information with 
code numbers; the samples are stripped of all personally identifying information, but a key linking 
the samples to clinical analysis data exists. This link means that the subject may be identified but 
only indirectly. The code numbers will be kept secure by or on behalf of the Sponsor. 


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Subjects who consented and provided a pharmacogenomic sample for DNA and RNA analysis can 
withdraw their consent and request disposal of a stored sample at any time prior to analysis. The 
Investigator will notify the sponsor of any subject who has withdrawn consent for the DNA and 
RNA analysis. 
9.5 
Blood Volume 
Direct venipuncture or intravenous cannula is the preferred method of blood collection. Any other 
method will need to be approved by the sponsor. The maximum volume of blood on any single 
day is approximately 111 mL, with the maximum amount not to exceed 500mL for the duration of 
study participation.  
9.6 
CSF Volume 
CSF will be collected by lumbar puncture, performed by a skilled and qualified individual. The 
maximum volume of CSF to be collected will be approximately 10 mL per subject.  
9.7 
Definitions 
9.7.1 PTE 
A PTE is defined as any untoward medical occurrence in a clinical investigation subject who has 
signed the ICF to participate in a study but prior to administration of any study medication; it does 
not necessarily have to have a causal relationship with study participation. 
9.7.2 AE 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a drug; it does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (e.g., a CS abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a drug whether or not it is 
considered related to the drug. 
9.7.3 Additional Points to Consider for PTEs and AEs 
An untoward finding generally may: 
 Indicate a new diagnosis or unexpected worsening of a pre-existing condition. (Intermittent 
events for pre-existing conditions underlying disease should not be considered PTEs or AEs) 
 Necessitate therapeutic intervention 
 Require an invasive diagnostic procedure 
 Require discontinuation or a change in dose of study medication or a concomitant medication 
 Be considered unfavorable by the Investigator for any reason 


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 PTEs/AEs caused by a study procedure (e.g., a bruise after blood draw) should be recorded as 
a PTE/AE 
Diagnoses vs. signs and symptoms: 
 Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as a PTE(s) or as an AE(s). 
Laboratory values and ECG findings: 
 Changes in laboratory values or ECG parameters are only considered to be PTEs or AEs if 
they are judged to be CS (i.e., if some action or intervention is required or if the Investigator
judges the change to be beyond the range of normal physiologic fluctuation). A laboratory re-
test and/or continued monitoring of an abnormal value are not considered an intervention. In 
addition, repeated or additional noninvasive testing for verification, evaluation, or monitoring 
of an abnormality is not considered an intervention
 If abnormal laboratory values or ECG findings are the results of pathology for which there is 
an overall diagnosis (e.g., increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as a PTE or as an AE 
Pre-existing conditions: 
 Pre-existing conditions (present at the time of signing of the ICF) are considered concurrent 
medical conditions and should NOT be recorded as PTEs or AEs. Baseline evaluations (e.g.,
laboratory tests, ECG, X-rays, etc.) should NOT be recorded as PTEs unless related to study 
procedures.  
 If a subject has a pre-existing episodic condition (e.g., asthma, epilepsy), any occurrence of an 
episode should only be captured as a PTE/AE if the episodes become more frequent, serious,
or severe in nature; that is, Investigators should ensure that the AE term recorded captures the 
change in the condition from Baseline (e.g., “worsening of…”)
 If a subject has a concurrent degenerative condition (e.g., cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater extent 
than that which would be expected. Again, Investigators should ensure that the AE term 
recorded captures the change in the condition (e.g., “worsening of…”) 
Worsening of PTEs or AEs: 
 If the subject experiences a worsening or complication of a PTE after starting administration 
of the study medication, the worsening or complication should be recorded appropriately as an 
AE.  


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 If the subject experiences a worsening or complication of an AE after any change in study 
medication, the worsening or complication should be recorded as a new AE. Changes in 
severity of AEs /Serious PTEs: 
 If the subject experiences changes in the severity of an AE/serious PTE, the event should be 
captured once, with the maximum severity recorded 
Preplanned surgeries or procedures: 
 Preplanned procedures (surgeries or therapies) that were scheduled prior to signing informed 
consent are not considered PTEs or AEs. However, if a preplanned procedure is performed 
early (e.g., as an emergency) due to a worsening of the pre-existing condition, the worsening 
of the condition should be captured appropriately as a PTE or an AE. Complications resulting 
from any planned surgery should be reported as AEs.
Elective surgeries or procedures:
 Elective procedures performed where there is no change in the subject’s medical condition 
should not be recorded as PTEs or AEs but should be documented in the subject’s source 
documents. Complications resulting from an elective surgery should be reported as AEs 
Overdose: 
 Cases of overdose with any medication without manifested side effects are NOT considered 
PTEs or AEs, but instead will be documented on an Overdose page of the eCRF. Any 
manifested side effects will be considered PTEs or AEs and will be recorded on the AE page 
of the eCRF 
9.7.4 SAEs 
An SAE is defined as any untoward medical occurrence that at any dose: 
1. Results in DEATH. 
2. Is LIFE-THREATENING 
 The term “life-threatening” refers to an event in which the subject was at risk of death at 
the time of the event; it does not refer to an event that hypothetically might have caused 
death if it were more severe 
3. Requires inpatient HOSPITALIZATION or prolongation of existing hospitalization 
4. Results in persistent or significant DISABILITY/INCAPACITY 


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5. Leads to a CONGENITAL ANOMALY/BIRTH DEFECT Is an IMPORTANT MEDICAL 
EVENT that may not result in death, be life-threatening or require hospitalization may be 
considered serious when, based on the appropriate medical judgment, satisfies any of the 
following: 
 May require intervention to prevent items 1 through 5 above 
 May expose the subject to danger, even though the event is not immediately life-
threatening or fatal or does not result in hospitalization,
o Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.
PTEs that fulfill 1 or more of the serious criteria above are also considered SAEs and should be 
reported and followed up in the same manner (see Sections 9.8.1 and 9.8.2). 
9.7.5 Severity of PTEs and AEs 
The different categories of intensity (severity) are characterized as follows: 
Mild: 
The event is transient and easily tolerated by the subject. 
Moderate: 
The event causes the subject discomfort and interrupts the subject’s usual activities.
Severe: 
The event causes considerable interference with the subject’s usual activities. 
9.7.6 Causality of AEs 
The relationship of each AE to study medication(s) will be assessed using the following categories:
Related: 
An AE that follows a reasonable temporal sequence from the administration of a drug 
(including the course after withdrawal of the drug), or for which possible involvement of the 
drug can be argued, although factors other than the drug, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments, may also be responsible. 
Not Related:
An AE that does not follow a reasonable temporal sequence from the administration of a drug 
and/or that can reasonably be explained by other factors, such as underlying diseases, 
complications, concomitant drugs, and concurrent treatments. 
 
 
9.7.7 Relationship to Study Procedures
Relationship (causality) to study procedures should be determined for all PTEs and AEs. 
The relationship should be assessed as Related if the Investigator considers that there is a 
reasonable possibility that an event is due to a study procedure. Otherwise, the relationship should 
be assessed as Not Related.


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9.7.8
Start Date 
The start date of the AE/PTE is the date that the first signs/symptoms were noted by the subject 
and/or physician.
9.7.9 Stop Date  
The stop date of the AE/serious PTE is the date at which the subject recovered, the event resolved 
but with sequelae, or the subject died. 
9.7.10 Frequency  
Episodic AEs/serious PTE (e.g., vomiting) or those which repeatedly occur over a period of 
consecutive days are intermittent. All other events are continuous. 
9.7.11 Action Concerning Study Medication  
 Drug withdrawn – a study medication is stopped due to the particular AE 
 Dose not changed – the particular AE did not require stopping a study medication 
 Unknown – only to be used if it has not been possible to determine what action has been taken
 Not Applicable – a study medication was stopped for a reason other than the particular AE,
e.g., the study has been terminated, the subject died, dosing with study medication was already 
stopped before the onset of the AE
9.7.12 Outcome 
 Recovered/Resolved – Subject returned to first assessment status with respect to the 
AE/serious PTE
 Recovering/Resolving – the intensity is lowered by one or more stages: the diagnosis or 
signs/symptoms has almost disappeared; the abnormal laboratory value improved but has not 
returned to the normal range or to baseline; the subject died from a cause other than the 
particular AE/serious PTE with the condition remaining “recovering/resolving” 
 Not recovered/not resolved – there is no change in the diagnosis, signs or symptoms; the 
intensity of the diagnosis, signs/ symptoms, or laboratory value on the last day of the observed 
study period had got worse than when it started; is an irreversible congenital anomaly; the 
subject died from another cause with the particular AE/serious PTE state remaining “Not 
recovered/not resolved.” 
 Resolved with sequelae – the subject recovered from an acute AE/serious PTE but was left 
with permanent/significant impairment (e.g., recovered from a cardiovascular accident but 
with some persisting paresis 
 Fatal – the AEs/PTEs which are considered as the cause of death 


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 Unknown – the course of the AE/serious PTE cannot be followed up due to hospital change or 
residence change at the end of the subject’s participation in the study 
9.8 
Procedures 
9.8.1 Collection and Reporting of AEs
9.8.1.1 PTE and AE Collection Period
Collection of PTEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject is first administered study medication Day 1 
or until screen failure. For subjects who discontinued prior to study medication administration, 
PTEs will be collected for the duration of study participation. 
Collection of AEs will commence from the time that the subject is first administered study 
medication Day 1. Routine collection of AEs will continue until 14 days following last dose. 
9.8.1.2 PTE and AE Reporting 
At each study visit, the Investigator or designee will assess whether any subjective AEs have 
occurred. A neutral question, such as “How have you been feeling since your last visit?” may be 
asked. Subjects may report AEs occurring at any other time during the study. Subjects 
experiencing a serious PTE must be monitored until the symptoms subside and any clinically 
relevant changes in laboratory values have returned to baseline, or there is a satisfactory 
explanation for the change. Non-serious PTEs, related or unrelated to the study procedure, need 
not be followed up for the purposes of the protocol.
All subjects experiencing AEs, whether considered associated with the use of the study medication 
or not, must be monitored until the symptoms subside and any clinically relevant changes in 
laboratory values have returned to baseline or until there is a satisfactory explanation for the 
changes observed. All PTEs and AEs will be documented in the PTE/AE page of the eCRF, 
whether or not the Investigator concludes that the event is related to the drug treatment. The 
following information will be documented for each event:
1. Event term 
2. Start and stop date and time 
3. Frequency 
4. Severity 
5. Investigator’s opinion of the causal relationship between the event and administration of study 
medication(s) (related or not related) (not completed for PTEs)
6. Investigator’s opinion of the causal relationship to study procedure(s), including the details of 
the suspected procedure 
7. Action concerning study medication (not applicable for PTEs) 


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8. Outcome of event
9. Seriousness
9.8.2 Collection and Reporting of SAEs 
When an SAE occurs through the AE collection period, it should be reported according to the 
following procedure:
An SAE form must be completed in English and signed by the Investigator immediately or within 
24 hours of the first onset or notification of the event. The information should be completed as 
fully as possible but contain, at a minimum:
 A short description of the event and the reason why the event is categorized as serious 
 Subject identification number 
 Investigator’s name
 Name of the study medication(s)
 Causality assessment
The SAE form should be transmitted within 24 hours to the attention of the contact listed in Section 
1.0. 
Any SAE spontaneously reported to the Investigator following the AE collection period should be 
reported to the sponsor if considered related to study participation. 
Reporting of Serious PTEs will follow the procedure described for SAEs. 
9.8.3 Reporting of Abnormal LFT 
If a subject is noted to have ALT or AST elevated >3 ×ULN on 2 consecutive occasions, the 
abnormality should be recorded as an AE. In addition, an LFT Increases eCRF must be completed 
by providing additional information on relevant recent history, risk factors, clinical signs and 
symptoms, and results of any additional diagnostic tests performed. 
If a subject is noted to have ALT or AST >3 ×ULN and total bilirubin >2 ×ULN for which an 
alternative etiology has not been identified, the event should be recorded as an SAE and reported 
as per Section 9.8.2. The Investigator must contact the Medical Monitor for discussion of the 
relevant subject details and possible alternative etiologies, such as acute viral hepatitis A or B or 
other acute liver disease or medical history/concurrent medical conditions. Follow-up laboratory 
tests as described in Section 9.1.8 must also be performed. In addition, an LFT Increases eCRF 
must be completed and transmitted with the SAE form (as per Section 9.8.3). 
 
 


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9.9
Follow-up of SAEs
If information is not available at the time of the first report becomes available at a later date, the 
Investigator should complete a follow-up SAE form or provide other written documentation and 
fax it immediately within 24 hours of receipt. Copies of any relevant data from the hospital notes 
(e.g., ECGs, laboratory tests, discharge summary, postmortem results) should be sent to the 
addressee if requested. 
All SAEs should be followed up until resuspension or the permanent outcome of the event. The 
timelines and procedures for follow-up reports are the same as those for the initial report. 
9.9.1 Safety Reporting to Investigators, IRBs or IECs, and Regulatory 
Authorities  
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities and IRBs or IECs, as 
applicable, in accordance with national regulations in the countries where the study is conducted. 
Relative to the first awareness of the event by/or further provision to the sponsor or sponsor’s 
designee, SUSARs will be submitted to the regulatory authorities as an expedited report within 7 
days for fatal and life-threatening events and 15 days for other serious events, unless otherwise 
required by national regulations. The sponsor will also prepare an expedited report for other safety 
issues that might materially alter the current benefit-risk assessment of an investigational 
medicinal product or that would be sufficient to consider changes in the investigational medicinal 
products administration or in the overall conduct of the trial. The investigational site also will 
forward a copy of all expedited reports to his or her IRB or IEC in accordance with national 
regulations. 
10.0 
STUDY-SPECIFIC COMMITTEES 
The Safety Review Group (SRG) will be comprised of the Investigator, Medical Monitor, 
Cerevance Medical Officer and may include other sponsor representatives. A pharmacokineticist 
and other subject matter experts may participate as needed. The responsibilities of the SRG are 
outlined in Section 6.1.3.
11.0 
DATA HANDLING AND RECORDKEEPING 
AEs, PTEs, medical history, and concurrent conditions will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Drugs will be coded using the World Health Organization 
(WHO) Drug Dictionary. All terms will be coded using the dictionary version available at the start 
of the study. 
11.1 
CRFs (Electronic) 
Completed eCRFs are required for each subject who signs an informed consent. 


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The sponsor or its designee will supply investigative sites with access to eCRFs. The sponsor will 
make arrangements to train appropriate site staff in the use of the eCRF. These forms are used to 
transmit the information collected in the performance of this study to the sponsor and regulatory 
authorities. eCRFs must be completed in English. Data are transcribed directly onto eCRFs.
After completion of the entry process, computer logic checks will be run to identify items, such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by sponsor
personnel (or designees) and will be answered by the site. 
Corrections to eCRFs are recorded in an audit trail that captures the old information, the new 
information, identification of the person making the correction, the date the correction was made, 
and the reason for the change. Reasons for significant corrections should additionally be included.  
The Investigator must review the eCRFs for completeness and accuracy and must sign and date 
the appropriate eCRFs as indicated. Furthermore, the Investigator must retain full responsibility 
for the accuracy and authenticity of all data entered on the eCRFs. 
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The sponsor or its designee will be permitted to review the subject’s medical 
and hospital records pertinent to the study to ensure the accuracy of the eCRFs. The completed 
eCRFs are the sole property of the sponsor and should not be made available in any form to third 
parties, except for authorized representatives of appropriate governmental health or regulatory 
authorities, without the written permission of the sponsor.
11.2 
Record Retention 
The Investigator agrees to keep the records stipulated in Section 11.2 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating subjects, medical records, temporary media such as thermal sensitive paper, source 
worksheets, all original signed and dated ICFs, subject authorization forms regarding the use of 
personal health information (if separate from the ICFs), an electronic copy of eCRFs, including 
the audit trail, and detailed records of drug disposition to enable evaluations or audits from 
regulatory authorities, the sponsor or its designees. Any source documentation printed on 
degradable thermal sensitive paper should be photocopied by the site and filed with the original in 
the subject’s chart to ensure long-term legibility. Furthermore, ICH E6 Section 4.9.5 requires the 
Investigator to retain essential documents specified in ICH E6 (Section 8) until at least 2 years 
after the last approval of a marketing application for a specified drug indication being investigated 
or, if an application is not approved, until at least 2 years after the investigation is discontinued 
and regulatory authorities are notified. In addition, ICH E6 Section 4.9.5 states that the study 
records should be retained until an amount of time specified by applicable regulatory requirements 
or for a time specified in the Clinical Study Site Agreement between the Investigator and sponsor.
Refer to the Phase 1 Site Specifications document for the sponsor’s requirements on record 
retention. The Investigator should contact and receive written approval from the sponsor before 
disposing of such documents. 


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12.0
STATISTICAL METHODS
12.1 
Statistical and Analytical Plans
A statistical analysis plan (SAP) will be prepared and finalized prior to unblinding of the subject’s 
treatment assignment. This document will provide further details regarding the definition of 
analysis variables and analysis methodology to address all study objectives.
A targeted data review will be conducted prior to unblinding of the subject’s treatment assignment. 
This review will assess the accuracy and completeness of the study database, subject evaluability, 
and appropriateness of the planned statistical methods.
12.1.1 Analysis Sets 
Safety Set 
The Safety Analysis Set will consist of all subjects who are enrolled and receive study drug. 
Subjects in this analysis set will be used for demographic, baseline characteristics, and safety 
summaries.
PK Set 
The PK set will consist of all subjects who receive study drug and have at least 1 measurable 
plasma concentration.
If any subjects are found to be non-compliant in dosing schedule or with incomplete data, a 
decision will be made on a case-by-case basis as to their inclusion in the analysis but will be 
presented in the subject listings.
12.1.2 Analysis of Demographics and Other Baseline Characteristics
Descriptive statistics (N, mean, SD, median, minimum, and maximum) will be generated for 
continuous demographic variables and baseline characteristics variables (age, height, weight, and 
BMI) for pooled placebo, CVN766 dose level, CVN766 overall, and overall. The number and 
percentage of subjects in each class of the categorical demographic variables and baseline 
characteristics variables (gender, ethnicity, and race) will be tabulated for pooled placebo, each 
CVN766 dose level, CVN766 overall, and overall. Individual subject demographic and baseline 
characteristics data will be listed. 
Demographic variables of screen failure subjects and reasons for screen failures will be 
summarized overall for subjects who are screened but not enrolled in the study. Individual 
demographic characteristics, date of informed consent, and reason for screen failure will be listed.
 


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12.1.3 PK Analysis
The concentration of CVN766 in plasma and CSF will be summarized by dose over each scheduled 
sampling time using descriptive statistics. Individual concentration data versus time will be 
presented in a data listing. Individual and mean plasma and CSF concentration data will be 
presented graphically.  Descriptive statistics (arithmetic mean, SD, median, minimum and 
maximum) will be used to summarize the plasma and CSF PK parameters for CVN766. In 
addition, geometric mean and coefficient of variation will be computed.
The effect of fed/fasting state on PK and bioavailability of CVN766 will be characterized.
Plots of Cmax and AUCs, as well as dose-normalized Cmax and AUCs, versus doses, will be 
generated. 
Dose proportionality will be tested for CVN766 Cmax and AUCs using a power model.  
A more detailed analysis will be presented in the SAP. 
12.1.4 Safety Analysis 
12.1.4.1 AEs 
All AEs will be coded by system organ class (SOC) and preferred term (PT) using MedDRA. 
Treatment-emergent AEs with onset occurring within 30 days (onset date – last date of dose +1
-
emergent AEs will be summarized by pooled placebo, each CVN766 dose level and CVN766 
overall by SOC and PT. The following summary tables will be included in the report: summary of 
TEAEs and drug-related AEs, relationship of AEs to study drug (related vs. not-related), severity 
of AEs, and related AEs. AEs leading to study drug discontinuation and SAEs will be listed. Data 
listings will be provided for all AEs, including PTE, TEAEs, AEs leading to study drug 
discontinuation, and SAEs. All AEs will be listed.
12.1.4.2 Clinical Laboratory Evaluation
Individual results of laboratory tests from hematology, chemistry, and urinalysis that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and change from baseline to post-dose
laboratory data will be summarized for pooled placebo, each CVN766 dose level, and CVN766 
overall. All clinical laboratory data will be listed. 
12.1.4.3 Vital Signs
Individual results of vital signs that are abnormal and CS will be summarized and listed. Baseline, 
post-dose, and changes from Baseline in vital sign measurements will be summarized by pooled 
placebo, each CVN766 dose level, and CVN766 overall. All vital sign data will be provided in the 
data listings.


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12.1.4.4 ECGs
Individual results of quantitative ECG parameters from the 12-lead safety ECGs that are abnormal 
and CS will be summarized and listed. Baseline, post-dose, and changes from baseline in 
quantitative ECG parameters will be summarized by pooled placebo, each CVN766 dose level,
and CVN766 overall. Shift tables may be generated for the Investigator’s ECG interpretations that 
changed from baseline to the post-dose collections by the above groups. All ECG data will be 
provided in the data listings. 
12.1.4.5 Other Variables 
Physical exam findings and suicidal assessments will be presented in data listings. 
12.2 
Interim Analysis and Criteria for Early Termination 
No interim analysis is planned. 
12.3 
Determination of Sample Size 
The sample size chosen of 8 subjects per cohort (6 active: 2 placebo) is considered to be sufficient 
for the evaluation of the safety, tolerability, and PK of each cohort. The sample size was not based 
on statistical power considerations.  
13.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
13.1 
Study-Site Monitoring Visits 
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The Investigator and institution guarantee access to source documents by the sponsor or its 
designee (contract research organization) and by the IRB or IEC.
All aspects of the study and its documentation will be subject to review by the sponsor or designee 
(as long as blinding is not jeopardized), including but not limited to the Investigator’s Binder, 
study medication, subject medical records, informed consent documentation, documentation of 
subject authorization to use personal health information (if separate from the ICFs), and review of 
eCRFs and associated source documents. It is important that the Investigator and other study
personnel are available during the monitoring visits and that sufficient time is devoted to the 
process.
13.2
Protocol Deviations
The Investigator should not deviate from the protocol, except where necessary, to eliminate an 
immediate hazard to study subjects. Should other unexpected circumstances arise that require 
deviation from protocol-specified procedures, the Investigator should consult with the sponsor or 


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designee (and IRB or IEC, as required) to determine the appropriate course of action. There will 
be no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria.
The site should document all protocol deviations in the subject’s source documents. In the event 
of a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the subject, or confound interpretation of primary study 
assessment. A Protocol Deviation Form should be completed by the site and signed by the sponsor 
or designee for any significant deviation from the protocol.
Every attempt will be made to collect each PK blood sample at the designated time point, and the 
actual time of each blood sample will be recorded on the source document and eCRF. Table 12
defines the windows allowed for sample collections. 
Protocol Deviation Forms are to be completed for PK samples collected outside of the following 
intervals: 
Table 11 
Windows for PK Blood Sample Collection 
Minutes 
Nominal Sampling Time 
no more than 15 minutes pre-dose
0 hour 
±5 
immediately post-dose 
±10 
>6 hours to 12 hours post-dose 
±15 
>12 hours to 24 hours 
±30 
>24 hours
13.3 
Quality Assurance Audits and Regulatory Agency Inspections 
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an auditing 
visit. The auditor may ask to visit the facilities where laboratory samples are collected, where the 
medication is stored and prepared, and any other facility used during the study. In addition, there 
is the possibility that this study may be inspected by regulatory agencies, including those of 
Australia (i.e., Therapeutic Goods Administration [TGA]) and foreign governments (e.g., the 
FDA, the United Kingdom Medicines and Healthcare products Regulatory Agency, the 
Pharmaceuticals and Medical Devices Agency of Japan). If the study site is contacted for an 
inspection by a regulatory body, the sponsor should be notified immediately. The Investigator and 
institution guarantee access for quality assurance auditors to all study documents as described in 
Section 13.1.
14.0 
ETHICAL ASPECTS OF THE STUDY 
This study will be conducted with the highest respect for the individual subjects (i.e., subjects) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, 
and the ICH Harmonised Tripartite Guideline for GCP. Each Investigator will conduct the study 


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according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the “Responsibilities of the Investigator” that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and Investigator responsibilities.
14.1 
IRB and/or IEC Approval
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. Those Americas sites unwilling to provide names and titles of all 
members due to privacy and conflict of interest concerns should instead provide a Federal Wide 
Assurance Number or comparable number assigned by the Department of Health and Human 
Services. 
The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the Investigator’s Brochure, a copy of 
the ICFs, and, if applicable, subject recruitment materials and/or advertisements and other 
documents required by all applicable laws and regulations must be submitted to a central or local 
IRB or IEC for approval. The IRB’s or IEC’s written approval of the protocol and subject informed 
consent must be obtained and submitted to the sponsor or designee before the commencement of 
the study (i.e., before shipment of the sponsor-supplied drug or study-specific screening activity). 
The IRB or IEC approval must refer to the study by exact protocol title, number, and version date; 
identify versions of other documents (e.g., ICF) reviewed; and state the approval date. The sponsor 
will ship the drug/notify the site once the sponsor has confirmed the adequacy of site regulatory 
documentation and, when applicable, the sponsor has received permission from a competent 
authority to begin the trial. Until the site receives drug/notification, no protocol activities, 
including screening, may occur. 
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by subjects, local safety reporting requirements, reports, and 
updates regarding the ongoing review of the study at intervals specified by the respective IRB or 
IEC, and submission of the Investigator’s final status report to IRB or IEC. All IRB and IEC 
approvals and relevant documentation for these items must be provided to the sponsor or its 
designee. 
Subject incentives should not exert undue influence on participation. Payments to subjects must 
be approved by the IRB or IEC and sponsor. 
14.2 
Subject Information, Informed Consent, and Subject Authorization 
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 


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applicable laws and regulations. The ICF, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and disclosures 
of the subject’s personal and personal health information for purposes of conducting the study. 
The ICF and the subject information sheet (if applicable) further explain the nature of the study, 
its objectives, and potential risks and benefits, as well as the date informed consent is given. The 
ICF will detail the requirements of the subject and the fact that he or she is free to withdraw at any 
time without providing a reason and without prejudice to their other medical care. 
The Investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and if applicable, the subject authorization form. The ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) must be approved by both the IRB or IEC 
and the sponsor prior to use. 
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject. It is the 
responsibility of the Investigator to explain the detailed elements of the ICF, subject authorization 
form (if applicable), and subject information sheet (if applicable) to the subject. Information should 
be given in both oral and written form whenever possible and in the manner deemed appropriate 
by the IRB or IEC. In the event the subject is not capable of rendering adequate written informed 
consent, then the subject’s legally acceptable representative may provide such consent for the 
subject in accordance with applicable laws and regulations.
The subject, or the subject’s legally acceptable representative, must be given ample opportunity to 
(1) inquire about details of the study and (2) decide whether or not to participate in the study. If 
the subject, or the subject’s legally acceptable representative, determines they will participate in 
the study, then the ICF and subject authorization form (if applicable) must be signed and dated by 
the subject or the subject’s legally acceptable representative at the time of consent and prior to the 
subject entering into the study. The subject or the subject’s legally acceptable representative should 
be instructed to sign using their legal names, not nicknames, using blue or black ballpoint ink. The 
Investigator must also sign and date the ICF and subject authorization (if applicable) at the time 
of consent and prior to the subject entering into the study; however, the sponsor may allow a 
designee of the Investigator to sign to the extent permitted by applicable law. 
Once signed, the original ICF, subject authorization form (if applicable), and subject information 
sheet (if applicable) will be stored in the Investigator’s site file. The Investigator must document 
the date the subject signs the informed consent in the subject’s medical record. Copies of the signed 
ICF, the signed subject authorization form (if applicable), and the subject information sheet (if 
applicable) shall be given to the subject.
All revised ICFs must be reviewed and signed by relevant subjects or the relevant subject’s legally 
acceptable representative in the same manner as the original informed consent. The date the revised 
consent was obtained should be recorded in the subject’s medical record, and the subject should 
receive a copy of the revised ICF. 
Subjects who consented and provided a pharmacogenomic sample for DNA analysis can withdraw 


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their consent and request disposal of a stored sample at any time prior to analysis. Notify sponsor 
of consent withdrawal.
14.3 
Subject Confidentiality
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’s source data will only be linked to 
the sponsor’s clinical study database or documentation via a unique identification number. As 
permitted by all applicable laws and regulations, limited subject attributes, such as sex, age, or 
date of birth, and subject initials may be used to verify the subject and the accuracy of the subject’s 
unique identification number. 
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the Investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (e.g., FDA, Medicines and Healthcare products Regulatory Agency, 
Pharmaceuticals, and Medical Devices Agency), the sponsor’s designated auditors, and the 
appropriate IRBs and IECs to review the subject’s original medical records (source data or 
documents), including, but not limited to, laboratory test result reports, ECG reports, admission 
and discharge summaries for hospital admissions occurring during a subject’s study participation, 
and autopsy reports. Access to a subject’s original medical records requires the specific 
authorization of the subject as part of the informed consent process (see Section 14.2). 
Copies of any subject source documents that are provided to the sponsor must have certain 
personally identifiable information removed (i.e., subject name, address, and other identifier fields 
not collected on the subject’s eCRF).
14.4 
Publication, Disclosure, and Clinical Trial Registration Policy
14.4.1 Publication and Disclosure
The Investigator is obliged to provide the sponsor with complete test results and all data derived 
by the Investigator from the study. During and after the study, only the sponsor may make study 
information available to other study Investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and/or advertisements, is the sole responsibility of the sponsor.
The sponsor may publish any data and information from the study, including data and information 
generated by the Investigator, without the consent of the Investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and review 
of the document. All publications and presentations must be prepared in accordance with this 
section and the Clinical Study Site Agreement. In the event of any discrepancy between the 
protocol and the Clinical Study Site Agreement, the Clinical Study Site Agreement will prevail.
The sponsor may publish any data and information from the study (including data and information 
generated by the Investigator) without the consent of the Investigator. 


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14.4.2 Clinical Trial Registration 
In order to ensure that information on clinical trials reaches the public in a timely manner and to 
comply with applicable laws, regulations, and guidance, the sponsor will register this clinical trial
on ClinicalTrials.gov (and possibly on other publicly accessible websites) before the start of study. 
Sponsor contact information, along with the Investigator’s city, state, country, and recruiting 
status, will be registered and available for public viewing. Once subjects receive the Investigator
contact information, they may call the site and request enrollment into the trial. The investigative 
site(s) are encouraged to handle such trial inquiries according to their established subject screening 
process. If the caller asks additional questions beyond the topic of trial enrollment, they should be 
referred to the sponsor. 
14.4.3 Clinical Trial Results Disclosure  
If required at the conclusion of the study, the sponsor will post the results on ClinicalTrials.gov or 
other publicly accessible websites, as required by applicable national and local laws and/or 
regulations. 
14.5 
Insurance and Compensation for Injury
Each subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study subjects. 
Refer to the Clinical Study Site Agreement regarding the sponsor’s policy on subject compensation 
and treatment for injury. If the Investigator has questions regarding this policy, they should contact 
the sponsor or sponsor’s designee. 


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15.0
REFERENCES
FDA Guidance for Industry: Food-effect bioavailability and fed bioequivalence studies (Dec 
2002). 
FDA Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials 
for Therapeutics in Adult Healthy Volunteers. US Dept of Health and Human Services, Food 
and Drug Administration, Center for Drug Evaluation and Research. 06 July 2005. Publication 
No. 5541. 
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. First-in-human study with ACT-
539313, a novel selective orexin-1 receptor antagonist. Br J Clin Pharmacol. 2020 
Jul;86(7):1377-1386. doi: 10.1111/bcp.14251.
Kaufmann P, Ort M, Golor G, Kornberger R, Dingemanse J. Multiple-dose clinical pharmacology 
of the selective orexin-1 receptor antagonist ACT-539313. Prog Neuropsychopharmacol Biol 
Psychiatry. 2021 Jun 8;108:110166. doi: 10.1016/j.pnpbp.2020.110166.  
Salvadore G, Bonaventure P, Shekhar A, Johnson PL, Lord B, Shireman BT, Lebold TP, 
Nepomuceno D, Dugovic C, Brooks S, Zuiker R, Bleys C, Tatikola K, Remmerie B, Jacobs 
GE, Schruers K, Moyer J, Nash A, Van Nueten LGM, Drevets WC. Translational evaluation 
of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for 
panic in rodents and humans. Transl Psychiatry. 2020 Sep 7;10(1):308. doi: 10.1038/s41398-
020-00937-9.
 


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Appendix A: Schedule of Study Procedures
SAD Cohorts 1, 2, 3a*,4, 5
Screening 
Check-in 
Dosing & Observation Discharge (a)
Outpatient 
Visit 
Early 
Termination 
Follow-up  
Study Day:
-28 to -2  
Day -1  
Day 1 
Day 2 
Day 3 
Day 4 
Day 8
Day 14 (±2) (b)
Informed consent 
X
 
 
 
 
Inclusion/exclusion criteria
X 
X 
 
 
Demographics and medical history
X 
 
 
 
Medication history 
X 
 
 
 
Neurological Exam (o)
X
X
X
X
X
 
Physical examination 
X 
X 
 
 
 
X  
X
X 
 
Vital signs (c) 
X 
X 
X 
X 
X 
X 
X
X 
 
Weight, height, and BMI (d)
X
X
 
X
X
X
Urine drug screen 
X
X
Cotinine screen
X
 
 
 
Concomitant medications (e)
X 
X 
X 
X 
X 
X 
X
X 
X
Concurrent medical conditions 
X
X
 
 
 
 
Clinical laboratory tests (f)
X
X
X
X
X
X
X
X
Hepatitis panel and HIV antibody test
X
FSH (g)
X
Serum Pregnancy test (hCG) 
X
Urine Pregnancy test
X
CV Telemetry (n)
X
X
ECG (h)
X
X
X
X
X
X
X
X
PGx DNA sample collection (i)
X
PGx RNA collection (j)
X
PK blood collection (k)
X
X
X
X
X


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PGx=pharmacogenomic.(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must then be brought back to the clinic for re-
evaluation per the Investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose [within 1 hour and 30 minutes prior to 
dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the 
Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, Day 8, Early Termination (if applicable), 
and as appropriate at the  Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional tube (for blood serum) will be obtained on Day -1 and Day 2, and the collected 
serum will be stored at -70C to enable additional, retrospective analyses as needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours until 48 hours post-
dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) Whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be collected during the food effect period. 
(k) Blood samples for PK analyses will be collected at time points indicated in Table 6. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
(o) Neurological exam to consist of light touch, power in limbs, and brief cranial nerve examination. 
 
SAD Cohorts 1, 2, 3a*,4, 5 
 
Screening
Check-in
Dosing & Observation
Discharge (a)
Outpatient 
Visit
Early 
Termination 
Follow-up 
Study Day:  
-28 to -2  
Day -1  
Day 1 
Day 2 
Day 3 
Day 4 
Day 8
Day 14 (±2) (b)
Standardized pre-dose meal (S3 fed 
cohorts only) 
 
 
X 
 
Study drug dosing
X
PTE assessment (l) 
X 
X 
X 
 
 
 
 
AE assessment (m)
X
X
X
X
X
X
X


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Cohort 3 SAD
Fasted-Fed Crossover
Screening
Dosing and Observation 
Inpatient
D/C
Inpatient
No sooner than +14 days or 4 half-
lives of Day 8 visit
+4 
days 
post 
D/C
E/T 
F/U
Study Day:
Days 
-28 to -2
Day -1
Day 1
Day 2
Day 3 Day 4
 
 
Day 8 Day -1 Day 1 Day 2 Day 3 Day 4
Day 14 
(±2) 
(b)
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria
X
X
Admitted to the Clinic 
 
X
 
 
 
 
 
 
 
 
Demographics and medical history 
X 
 
 
 
 
 
 
 
 
 
Medication history
X
X
Neurological Exam (o)
X
X
X
X
X
X
X
X
X
X
Physical examination  
X 
X
 
 
 
X  
X 
X 
X 
X 
X
 
Vital signs (c)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight, height, and BMI (d)
X
X
X
X
X
X
X
X
Urine drug screen 
X 
X
 
 
 
 
 
X 
 
 
Cotinine screen
X
Concomitant medications (e)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concurrent medical conditions
X
X
X
Clinical laboratory tests (f)
X
X
X
X
X
X
X
X
X
X
X
X
X
Hepatitis panel and HIV antibody 
test
X
FSH (g)
X
Serum Pregnancy test (hCG) 
X
Urine Pregnancy test
X
X
CV Telemetry (n)
X
X
X
X
X
ECG (h)
X
X
X
X
X
X
X
X
X
X
X
X
X
PGx DNA sample collection (i)
X
PGx RNA collection (j)
X
X
PK blood collection (k)
X
X
X
X
X
X
X
X
X


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*S3 Cohort will return no sooner than Day 14 or 4 half-lives (whichever is greater) after Day 8 for the Fed portion. The Fed portion will commence on Day -1 
will all the same schedule of events with the exception of dosing will be post-meal.  
PGx=pharmacogenomic.
(a) Events listed as occurring at “Inpatient Discharge” visit will occur prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge.  
(b) The Follow-up Visit will occur by telephone on Day 14 (±2) unless abnormal CS findings were observed during previous visits. In these cases, subjects must then be brought back to the clinic for re-
evaluation per the Investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 (pre-dose [within 1 hour and 30 minutes prior to 
dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours through 72 hours post-dose, and at Outpatient Visit Day 8, or Early Termination (if applicable) and as appropriate at the 
Follow-up Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Day 1, Days 2 through 4, Day 8, Early Termination (if applicable), 
and as appropriate at the follow up visit Fasting lipase tests will be collected at Day -1, 24 hours and 48 hours post-dose. An additional tube (for blood serum) will be obtained on Day -1 and Day 2, and 
the collected serum will be stored at -70C to enable additional, retrospective analyses as needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Day 1 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-dose), and then every 12 hours until 48 hours post-
dose, Day 4, Day 8, Early Termination (if applicable) . 
(i) One blood sample will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) Whole blood samples will be collected on Day 1 (pre-dose, 8-, and 24-hours post-dose) for RNA pharmacogenomic analysis. Samples will also be collected during the food effect period. 
(k) Blood samples for PK analyses will be collected at time points indicated in Table 6. 
CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in selected cohorts as indicated in Table 9.  
(l) PTEs will be collected from signing of informed consent up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) CV telemetry should be recorded at least 12 hours prior to dosing, and up to 24 hours after dosing 
(o) Neurological exam to consist of light touch, power in limbs, and brief cranial nerve examination. 
 
Cohort 3 SAD
Fasted-Fed Crossover
Screening
Dosing and Observation 
Inpatient
D/C
Inpatient
No sooner than +14 days or 4 half-
lives of Day 8 visit
+4 
days 
post 
D/C 
E/T
F/U
Study Day: 
Days
-28 to -2 
Day -1
Day 1 
Day 2 Day 3 Day 4 
 
Day 8 Day -1 Day 1 Day 2 Day 3 Day 4
Day 14 
(±2) 
(b) 
Lumbar puncture & CSF collection 
(k)
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Standardized pre-dose meal 
X
Study drug dosing 
 
 
X 
 
 
 
 
 
X 
 
 
PTE assessment (l) 
X 
X
X 
 
 
 
 
X 
X 
 
 
AE assessment (m)
X
X
X
X
X
X
X
X
X
X
X
X
X
Discharged from Clinic 
 
 
 
 
 
X 
 
 
X 
X
 


CVN766
Study No. CVN766-101
Page 73 of 76
Clinical Protocol  - Version 4.0 
01 June 2022
CONFIDENTIAL
Multiple-Dose 
Regimen Cohorts
SCR
Check
-in 
Inpatient
Dosing & Observation
Inpatient 
Discharge 
(a)
Outpatient Visit
E/T Follow-up
Study Day: 
Days 
-28 to -2 Day -1 
Day  
1 
Day  
2 
Day  
3 
Day  
4 
Day  
5 
(model for 
additional 
dosing 
days) 
Day 6 
Day of 
last dose 
(e.g. 
Day7) 
1 day 
after last 
dose (e.g. 
Day 8) 
2 days after 
last dose (e.g. 
Day 9) 
3 days ±0 
after last 
dose (e.g. 
Day 10) (o) 
7 days ±1 
after last 
dose (e.g. 
Day 14) 
 
14 days ±2 
after last 
dose (e.g. 
Day 21 ±2) 
(b) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria
X
X
Demographics and 
medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neurological exam (p)
X
X
X
X
X
X
Physical examination 
X
X
X
X
X
X
X
Vital signs (c)
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight, height, and 
BMI (d) 
X 
X 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
Urine drug screen
X
X
Cotinine screen
X
Concomitant 
medications (e)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concurrent medical 
conditions
X
X
Clinical laboratory tests 
(f)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hepatitis panel and HIV 
antibody test
X
FSH (g)
X
Serum Pregnancy test 
(hCG) 
X
Urine Pregnancy Test
X
ECG (h)
X
X
X
X
X
X
X
X
X
X
X
X
X


CVN766
Study No. CVN766-101
Page 74 of 76
Clinical Protocol – Version 4.0 
01 June 2022
CONFIDENTIAL
Multiple-Dose 
Regimen Cohorts 
SCR
 
Check
-in 
 
Inpatient 
Dosing & Observation
 
Inpatient 
Discharge 
(a) 
 
Outpatient Visit
E/T Follow-up
 
Study Day:
Days 
-28 to -2 Day -1
Day  
1
Day  
2
Day  
3
Day  
4
Day  
5
(model for 
additional 
dosing 
days) 
Day 6
Day of 
last dose 
(e.g. 
Day7)
1 day 
after last 
dose (e.g. 
Day 8)
2 days after 
last dose (e.g. 
Day 9)
3 days ±0 
after last 
dose (e.g. 
Day 10) (o)
7 days ±1 
after last 
dose (e.g. 
Day 14)
14 days ±2 
after last 
dose (e.g. 
Day 21 ±2) 
(b)
PGx DNA sample 
collection (i)
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PGx RNA collection (j)
X
X
PK blood collection (k)
X
X
X
X
X
X
X
X
X
X
X
Study drug dosing 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
PTE assessment (l)
X
X
X
AE assessment (m)
X
X
X
X
X
X
X
X
X
X
X
X
X
PGx=pharmacogenomic (a) Events listed as occurring at “Inpatient Discharge” visit will occur on that day prior to formal “Inpatient Discharge” but not necessarily at the time of Discharge. 
(b) The Follow-up Visit will occur by telephone on Day 21 (±2) unless abnormal CS findings are observed upon discharge. In these cases, subjects must then be brought back to the clinic for re-
evaluation per Investigator’s discretion.  
(c) Vital signs (tympanic body temperature, respiration, pulse, and blood pressure) will be obtained at Screening, Inpatient Check-in (Day -1), Day 1 and Day 7 (pre-dose [within 1 hour and 30 minutes 
prior to dosing], and at 1, 2, 4-, 6-, 8-, and 12-hours post-dose), Days 2 through 6 (pre-dose and 12 hours post-dose), Day 8, Day 9, Early Termination (if applicable), and as appropriate at the Follow-up 
Visit Day 14 (±2 days). Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in Day-1) 15 minutes apart. 
(d) Height and BMI will be collected at Screening only. 
(e) Record all ongoing medications from Screening and throughout the study. 
(f) Fasting clinical laboratory tests (hematology, serum chemistry, urinalysis) will be collected at Screening, Day -1, prior to dosing on Days 1 through 8, Day 9, Early Termination (if applicable), and as 
appropriate at the Follow-up Visit Day 21 (±2 days). Fasting lipase tests will be collected at Day -1, Days 2, 7, and 8 (pre-dose). An additional tube (for blood serum) will be obtained on Day -1 and Day 
2, and the collected serum will be stored at -70C to enable additional, retrospective analyses as needed. 
(g) A FSH level will be obtained on post-menopausal women (defined as continuous amenorrhea of at least 2 years and not surgically sterile). 
(h) Triplicate standard 12-lead ECG will be recorded at Screening, Inpatient Check-in (Day -1), Days 1 and 7 (pre-dose [within 1 hour prior to dosing], and at 0.5, 1, 2, 4-, 6-, 8-, and 12-hours post-
dose), Days 2 through 6 (pre-dose and 12 hours post-dose), Days 8 and 9, Early Termination (if applicable), and as appropriate at the Follow-up Visit Day 21 (±2 days). 
(i) One blood sample will be collected for pharmacogenomic analysis prior to dosing on Day 1; this will only be collected once per subject. 
(j) Whole blood samples will be collected on Day 1 and Day 7 (pre-dose, 8- and 24-hours post-dose) for RNA pharmacogenomic analysis.  
(k) Blood samples for PK analyses will be collected at time points indicated in Table 7.  CSF samples (up to 10 mL) will be collected at 3 h post-dose by lumbar puncture only in Cohorts M1 and 
potentially M2, as indicated in Table 9. Cohort M3 also may, at SRG discretion, undergo PK sampling from CSF, the choice of day and sampling time to be decided by SRG. 
(l) PTEs will be collected from signing of ICF up until dosing on Day 1. 
(m) Any AE with onset or exacerbation after dosing on Day 1 will be captured as an AE.  
(n) 24-hour urine collection is only done for Cohort M1, predose on Day 1, and at three separate time points post-dose: 0-6h, 6-12h, and 12-24h on Day 1 and Day 7 Cohort(o) If emerging PK data 
indicate the CVN766 t½ is 15 hours (or less), the Day 10 visit is unnecessary.
(p) Neurological exam consists of light touch, power in limbs, and brief cranial nerve examination.
PPD
PPD


CVN766
Study No. CVN766-101
Page 75 of 76
Clinical Protocol  - Version 4.0
01 June 2022
CONFIDENTIAL 
Appendix B: Responsibilities of the Investigator
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. 
The Investigator agrees to assume the following responsibilities. 
1. Conduct the study in accordance with the protocol.
2. Personally conduct or supervise the staff who will assist in the protocol.
3. Ensure that study-related procedures, including study-specific (non-routine/nonstandard 
panel) screening assessments, are NOT performed on potential subjects prior to the receipt of 
written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the study are informed 
of these obligations. 
5. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conforms 
to local regulatory requirements. 
6. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and 
approval of the protocol. Promptly report to the IRB/IEC all changes in research activity and 
all anticipated risks to subjects. Make at least yearly reports on the progress of the study to 
the IRB/IEC and issue a final report within 3 months of study completion. 
7. Ensure that requirements for informed consent, as outlined in local regulations, are met. 
8. Obtain valid ICF from each subject who participates in the study and document the date of 
consent in the subject’s medical chart. Valid informed consent is the most current version 
approved by the IRB/IEC. Each ICF should contain a subject authorization section that 
describes the uses and disclosures of a subject’s personal information (including personal 
health information) that will take place in connection with the study. If an ICF does not 
include such a subject authorization, then the Investigator must obtain a separate subject 
authorization form from each subject or the subject’s legally acceptable representative.
9. Prepare and maintain adequate case histories of all persons entering into the study, including 
eCRFs, hospital records, laboratory results, etc., and maintain these data for a minimum of 
2 years following notification by the sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The Investigator should 
contact and receive written approval from the sponsor before disposing of any such 
documents. 
10. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents. 
11. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor.  
12. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours. 


CVN766
 
Study No. CVN766-101
Page 76 of 76
Clinical Protocol – Version 4.0
01 June 2022
CONFIDENTIAL 
Appendix C: Investigator Consent to Use of Personal Information  
Cerevance will collect and retain personal information of the Investigator, including their name, 
address, and other personally identifiable information. In addition, Investigator’s personal 
information may be transferred to other parties located in countries throughout the world (e.g.,
the United Kingdom, United States, and Japan), including the following:
 Cerevance, its affiliates, and licensing partners
 Business partners assisting Cerevance, its affiliates, and licensing partners 
Regulatory agencies and other health authorities
IRBs and IECs
Investigator’s personal information may be retained, processed, and transferred by Cerevance
and these other parties for research purposes, including the following:
Assessment of the suitability of Investigator for the study and/or other clinical studies
Management, monitoring, inspection, and audit of the study
 Analysis, review, and verification of the study results 
 Safety reporting and pharmacovigilance relating to the study 
 Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study 
 Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may 
contain the same chemical compound present in the study medication 
 Inspections and investigations by regulatory authorities relating to the study
 Self-inspection and internal audit within Cerevance, its affiliates, and licensing partners
 Archiving and audit of study records 
 Posting Investigator site contact information, study details, and results on publicly accessible 
clinical trial registries, databases, and websites 
 Investigator’s personal information may be transferred to other countries that do not have 
data protection laws that offer the same level of protection as data protection laws in the 
Investigator’s own country. 
 Investigator acknowledges and consents to the use of their personal information by 
Cerevance and other parties for the purposes described above. 
 

SAP_001.pdf: 
Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  1  of 4 6  
T he i nf or m ati o n i n t his d oc u me nt is c o nfi de nti al a n d pr o priet ar y t o N o v otec h Pt y Lt d a n d its 
clie nts. T he i nf or m ati o n m a y  o nl y  be  use d  b y  t he e ntities t o w hic h  it w as  discl ose d  f or t he p ur p ose 
it w as discl ose d. T o t he m a xi m u m e xte nt per missi ble b y l a w, t he i nf or m ati o n m ust n ot be 
discl ose d t o a n y t hir d p arties wit h o ut t he pri or writte n c o nse nt of N o v otec h.  
S T A TI S TI C A L  A N A L Y SI S  P L A N  
A P h ase 1, R a n d o mize d, D o u ble -Bli n d, Pl ace b o - C o ntr olle d, S afet y, T oler a bilit y, a n d 
P h ar m ac o ki netic  St u d y  of Esc al ati n g Si n gle  a n d  M ulti ple  D oses  of C V N 7 6 6 i n He alt h y 
S u bjects  
P R O T O C O L  N O.:  
C V N 7 6 6 -1 0 1  
P R O D U C T  C O D E : C V N 7 6 6  
P R E P A R E D  F O R:  
Cere va nce  Ga m ma, I nc. 
O ne  Mar i na Par k  Dri ve,  S uite  1 4 1 0 
B ost o n, M A 0 2 2 1 0 
U nite d  S tates 
P R E P A R E D  B Y:  
N o v otec h ( A ustralia) Pt y  Lt d  
Le vel  3, 2 3 5 P yr m o nt Street  
P yr m o nt, N S W,  2 0 0 9 
A ustralia  
D A T E  O F I S S U E: 
2 0 2 2 - 1 0-2 0  
V E R SI O N/ S T A T U S:  
V ersi o n 1. 0  
V E R SI O N HI S T O R Y:  Ve rsi o n 1. 0  (2 0 2 2 - 1 0-2 0 ) 
A U T H O R:  
 
N C T N u m ber: N C T 0 5 1 0 5 2 4 3
T his N C T n u m ber has bee n a p plie d t o t he d oc u me nt f or p ur p oses of p osti n g o n Cli nicaltrials. g o v
P P D


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  2  of 4 6  
 
 
 
S A P  A P P R O V A L  
 
B y m y  si g nat ure, I c o nfir m t hat t his S A P  has  bee n  re vie we d b y  a n d has  bee n  a p pr o ve d  f or use  o n  t he 
C V N 7 6 6 -1 0 1  st u d y: 
 
N a me  
Title / C o m p a n y  
Si g n at ure  
D ate  
 
 
 
Pre pare d B y: 
 
Bi ostatisticia n/  N o v otec h  Pt y . 
Lt d.  
 
El e ctr o ni c all y  si g n e d  b y:
R e a s o n: I a m t h e A ut h or
D at e:  O ct 2 1,  2 0 2 2  0 9: 0 3  G M T + 1 1  
 
 
 
Re vie we d b y: 
 
P har mac o metricia n/ 
N o v ote c h Pt y. Lt d. 
 
El e ctr o ni c all y si g n e d b y:
R e a s o n: I h a v e r e vi e w e d  
D at e:  O ct 2 1,  2 0 2 2  1 3: 1 0  G M T + 1 1  
 
 
 
Re vie we d b y: 
 
 
Ma na ger  Bi ostatistics/  N o v otec h 
Pt y. Lt d.  
 
 
El e ctr o ni c all y  si g n e d  b y:
R e a s o n: I h a v e r e vi e w e d  
D at e:  O ct  2 1,  2 0 2 2  0 8: 5 8  G M T + 5. 5  
 
 
 
A p pr o ve d  b y: 
 
Me dical M o nit or / 
Cere va nce  G a m ma I nc. 
 
El e ctr o ni c all y si g n e d  b y:
R e a s o n: I a p pr o v e  
D at e: O ct 2 1, 2 0 2 2 0 0: 3 9 G M T + 2  
 
 
 
A p pr o ve d b y: 
 
Direct or,  Hea d  of  D M P K/ 
C ere va nce Ga m ma I nc.  
El e ctr o ni c all y  si g n e d  b y:
R e a s o n: I h a v e r e vi e w e d  
D at e:  O ct  2 1,  2 0 2 2  0 9: 0 3  G M T + 1  
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


Protocol Number: CVN766-101 
Document status: Version 1.0 
2022-10-20 
Novotech - Strictly Confidential 
Page 3 of 46 
 
 
 
Table of contents 
1. 
INTRODUCTION 
7 
2. 
PROJECT OVERVIEW 
8 
2.1 
Study Design 
8 
2.2 
Objectives 
9 
2.3 
Endpoints 
10 
2.4 
Sample Size 
10 
2.5 
Randomization 
10 
3. 
STATISTICAL CONSIDERATIONS 
11 
3.1 
General Considerations 
11 
3.2 
Key Definitions 
12 
3.3 
Inferential Analyses 
13 
3.4 
Multiple Comparisons and Multiplicity Adjustments. 
14 
3.5 
Handling of Missing Data 
14 
3.6 
Coding of Events and Medications 
16 
3.7 
Treatment Groups 
16 
4. 
ANALYSIS SETS 
18 
4.1 
Population Descriptions 
18 
5. 
PARTICIPANT DISPOSITION AND ANALYSIS POPULATIONS 
19 
6. 
PROTOCOL DEVIATIONS 
20 
7. 
DEMOGRAPHIC AND BASELINE INFORMATION 
21 
7.1 
Demographics 
21 
7.2 
Medical /Surgical history 
21 
7.3 
Hepatitis panel and HIV Antibody Test 
21 
7.4 
Alcohol, Urine Drug & Cotinine Screen Test 
21 
7.5 
Follicle stimulating hormone (FSH) Test 
21 
7.6 
Pregnancy Test (Serum and Urine) 
21 
8. 
TREATMENT EXPOSURE 
22 
9. 
PRIOR AND CONCOMITANT MEDICATIONS 
23 
10. 
PHARMACOKINETICS 
24 
10.1 
Collection of Plasma/Serum Samples for PK Analysis SAD 
24 
10.2 
Collection of Plasma/Serum Samples for PK Analysis MAD 
24 
10.3 
Collection of CSF Samples for PK Analysis SAD and MAD 
24 
10.4 
Collection of Urine Samples for PK Analysis MAD 
25 
10.5 
Pharmacokinetic Parameters 
25 
10.6 
Urine PK Parameters MAD 
28 
10.7 
Criteria for the Calculation of an Apparent Terminal Elimination Half-Life 
29 


Protocol Number: CVN766-101 
Document status: Version 1.0 
2022-10-20 
Novotech - Strictly Confidential 
Page 4 of 46 
 
 
 
11. 
SAFETY 
32 
11.1 
Adverse Events 
32 
11.2 
Safety Laboratory Assessments 
32 
11.3 
Vital Signs 
34 
11.4 
12-Lead Electrocardiogram (ECG) 
35 
11.5 
CV Telemetry 
36 
11.6 
Neurological Exam 
36 
11.7 
Physical Examinations 
36 
12. 
CHANGES TO THE PLANNED ANALYSIS 
36 
• 
INTERIM AND FINAL ANALYSIS 
37 
12.1 
Final Analysis (End of Study) 
37 
13. 
SOFTWARE 
38 
14. 
TABLES 
39 
15. 
LISTINGS 
41 
16. 
FIGURES 
44 
17. 
REFERENCES 
46 


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  5  of 4 6  
 
 
 
List  of  A b bre vi ati o ns  
 
A b bre vi ati o n  
Descri pti o n  
 
λz  
 
Ter mi nal  Eli mi nati o n  Rate  C o nsta nt  
A E  
A d verse  E ve nt  
A L T  
Ala ni ne  A mi n otra nsferase  
A S T  
As partate  A mi n otra nsferase  
A T C  
A nat o mical  T hera pe utic  Class  
A U C  
Area  u n der  t he c ur ve 
A U C 2 4  
Area  u n der  t he plas ma  c o nce ntrati o n -ti me c ur ve fr o m ti me 0  t o 2 4  h o urs  
A U C 0- i nf 
Area  u n der  t he plas ma  c o nce ntrati o n -ti me c ur ve fr o m ti me 0  t o i nfi nit y 
A U C ta u 
Area  u n der  c o nce ntrati o n -ti me c ur ve o ver  d osi n g  i nter val 
A U C t 
Area  u n der  t he plas ma  c o n ce ntrati o n -ti me c ur ve 
B MI  
B o d y  mass  i n de x 
B Q L  
Bel o w  t he q ua ntitati o n  li mit 
C L/ F  
A p pare nt  cleara nce after e xtra vasc ular  a d mi nistrati o n 
C L/ F ss 
A p pare nt  cleara nce after e xtra vasc ular  a d mi nistrati o n  at stea d y state 
 
 
C ma x  
Ma xi m u m  o bser ve d  plas ma  c o nce ntrati o n 
C mi n  
Mi ni m u m  o bser ve d  plas ma  c o nce ntrati o n 
C N S  
Ce ntral  ner v o us  s yste m 
C S  
Cli nicall y  Si g nifica nt  
C ss, ma x 
Ma xi m u m  o bser ve d  plas ma  c o nce ntrati o n  at stea d y state 
C ss, mi n 
Mi ni m u m  o bser ve d  plas ma  c o nce ntrati o n  at stea d y state 
C S R  
Cli nical  St u d y  Re p ort  
C tr o u g h 
Pre -d ose  Tr o u g h  C o nce ntrati o n  
C V  
C oefficie nt  of  Variati o n  
D B P  
Diast olic  bl o o d  press ure  
E C G  
1 2 -Lea d  Electr ocar di o gra m  
e C R F 
Electr o nic  Case  Re p ort  F or m  
F E  
F o o d  Effect  
F S H  
F ollicle -sti m ulati n g h or m o ne  
G C P  
G o o d  Cli nical  Practice  
HI V  
H u ma n  I m m u n o deficie nc y Vir us  
M A D  
M ulti ple -asce n di n g d ose  
Me d D R A  
Me dical  Dicti o nar y  f or Re g ulat or y  Acti vities  
N/ A  
N ot  A p plica ble  
N C S  
N ot  Cli nicall y  Si g nifica nt  
N K  
N ot  K n o w n  
PI  
Pri nci pal  I n vesti gat or 
P D  
P har mac o d y na mic  
P K  
P har mac o ki netic  
P T  
Preferre d  Ter m  
Q Tc B  
Q T  i nter val wit h  Bazett’s  c orrecti o n  met h o d  
Q Tc F  
Q T  i nter val wit h  Fri dericia’s  c orrecti o n  met h o d  
R acc 
Acc u m ulati o n  rati o 
S A D  
Si n gle  Asce n di n g  D ose  
S A E  
Seri o us  A d verse  E ve nt  
S A P  
Statistical  A n al ysis  Pla n  
S B P  
S yst olic  bl o o d  press ure  
S D  
Sta n dar d  De viati o n  
S.I.  
I nter nati o nal S yste m  of  U nits  
P P
D


Protocol Number: CVN766-101 
Document status: Version 1.0 
2022-10-20 
Novotech - Strictly Confidential 
Page 6 of 46 
 
 
 
 
Abbreviation 
Description 
 
SOC 
 
System Organ Class 
SOP 
Standard Operating Procedure 
SRC 
Safety Review Committee 
t1/2z 
Terminal elimination half-life 
TEAE 
Treatment Emergent Adverse Event 
Tmax 
Time to maximum concentration 
Tss, max 
Time for Cmax at steady state. 
Vz/F 
Apparent volume of distribution after extravascular administration 
Vz/Fss 
Apparent volume of distribution after extravascular administration at steady state 
WHO-DD 
World Health Organization Drug Dictionary 
 


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1. 
INTRODUCTION 
The following Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of the data 
collected from the CVN766-101 study (protocol version 4.0 amendment 3 dated 19 May 2022). 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), regulatory 
submissions, or future manuscripts. Also, post hoc exploratory analyses not necessarily identified in this 
SAP may be performed to further examine study data. Any post hoc, or unplanned exploratory analyses 
performed will be clearly identified as such in the final CSR. 
CVN766 is a highly selective orexin-1 receptor (Ox1R) antagonist and may have utility as treatment for 
psychiatric disorders including schizophrenia, panic disorder and anxiety, and addiction. The present 
study will be the first conducted in humans with CVN766 and will examine the compound's safety, 
tolerability, and PK in healthy subjects. 


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2. 
PROJECT OVERVIEW 
 
2.1 
Study Design 
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending 
study in healthy subjects with concurrent PK sampling from blood plasma, urine, and cerebrospinal fluid. 
This study is formed by two parts: Part 1 (SAD) and Part 2 (MAD). 
 
2.1.1 Part 1: SAD is the single-dose regimen and Fasted- Fed Crossover 
Approximately 40 healthy male or female subjects will be enrolled in 1 of 5 single-dose cohorts 
(designated as S1 through S5, respectively) in an ascending fashion. An optional Cohort 3a may be added 
in parallel to SC3 for additional safety and tolerability evaluation. Cohort S3a dose level will be 
consistent with Cohort S3 (45 mg planned) in a fasted condition only and without lumbar puncture, 
aligned with other SAD cohorts. Each cohort will consist of 8 subjects randomized to CVN766 or 
placebo, whereby 6 subjects will receive a single oral dose of CVN766 suspension, and 2 subjects will 
receive a matching placebo suspension under overnight fasted conditions. Sentinel dosing (1 subject to 
receive CVN766 and 1 subject to receive placebo) will be used in each cohort to ensure adequate safety 
and tolerability evaluation prior to administering CVN766 or placebo to the remainder of the subjects 
within the cohort. The planned dose levels will be 5, 15, 45, 125, and 250 mg CVN766. Each following 
dose level may be higher, lower, or remain the same as the preceding cohort. Additional cohort(s) may 
be added if deemed necessary by the SRG to fully characterize the safety and tolerability of CVN766. 
To assess the effect of food on CVN766 bioavailability in suspension formulation, the single-dose 
administration will be repeated in a single cohort (S3) after ingestion of a standardized high-fat, high- 
calorie meal. Once the safety of the S3 cohort dose level has been assessed, the S3 cohort subjects will 
return to the clinic (no sooner than 14 days after their prior dose, or at least 4 half-lives, has lapsed based 
on preliminary PK data, whichever is longer). They will receive the same dose as before, administered 
after ingesting a standardized breakfast. Subjects will finish at least approximately 85% of their breakfast 
within 30 minutes and receive an investigational product 30 minutes (± 5 minutes) after beginning the 
meal. Sentinel dosing will not be required for subjects returning to the clinic for the fed regimen. If the 
CVN766 PK parameters in the fasted S3 cohort reveal poor absorption with inconclusive results, the fed 
cohort will be deferred until a higher dose level. 
On Day 1, subjects will undergo safety monitoring and PK sampling from blood plasma through 72 
hours post-dose and, for cohort S3 (fasted) only, from CSF via lumbar puncture at 3 hours post-dose 
 
2.1.2 Part 2 MAD is a Multiple-Dose Regimen 
Approximately 24 healthy male and female subjects aged 18 to 55 will be enrolled in 1 of the 3 multiple- 
dose cohorts (designated as M1 through M3, respectively) in an ascending fashion. The dose levels 
planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-dose 
cohorts M1 through M3, respectively. Each multiple-dose cohort will consist of 8 subjects randomized 
to CVN766 or placebo, whereby 6 subjects will receive a daily oral dose of CVN766, and 2 subjects will 
receive matching placebo for 7 days. Dosing will be administered in the fasting state; the SRG can change 
this if exposure is higher in the fed state. The planned dosing duration for the multiple-dose cohorts is 7 
days. However, the duration may be increased to ≤14 days if preliminary PK data suggest steady-state 
will not be achieved within 6 days of daily dosing. 
 
On Day 1 subjects, will undergo safety monitoring and PK sampling from blood plasma through 24 
hours post-dose and on Day 7, will undergo safety monitoring and PK sampling from blood plasma 
through 72 hours post-dose. Additionally, PK samples will be collected on Days 3, 4, 5 and 6 prior to 
the next planned dose. For cohort M1, on day 7 only, subjects will undergo PK sampling from CSF via 
lumbar puncture at 3 hours post dose and PK sampling from urine over 24 h on Day 1 and Day 7. CSF 
samples may also be taken from M2 and M3 cohorts at the SRG’s discretion. 


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  9  of 4 6  
 
 
 
Fi g ure  1:  
St u d y Desi g n  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. 2  
O bjecti ves 
Pri m ar y  o bjecti ve(s)  
• T o  c haracterize  t he safet y a n d t olera bilit y pr ofile of  escalati n g  d ose  le vels of  C V N 7 6 6  s us pe nsi o n w he n 
a d mi nistere d as a si n gle oral d ose or dail y oral d oses f or 7 da ys i n healt h y s u bjects.  
 
Sec o n d ar y  o bjecti ve(s)  
T he  sec on dar y  o bjecti ves  of  t his st u d y are: 
• T o  c haracterize  t he si n gle-d ose  P K  pr ofile of  C V N 7 6 6  i n plas ma,  a n d C S F  
• T o  c haracterize  t he m ulti ple -d ose  P K  pr ofile of  C V N 7 6 6  i n plas ma,  a n d C S F  
• T o  assess t he effect of  f o o d o n  t he bi oa vaila bilit y  of  C V N 7 6 6  i n t he c urre nt f or m ulati o n 
 
E x pl or at or y  o bjecti ve(s)  
T he  ex pl orat or y  o bjecti ves  of  t his st u d y are: 
•  
T o e x pl ore p ossi ble dr u g meta b olic e nz y me a n d tra ns p orter p ol y m or p his ms t hat ma y c o ntri b ute t o 
varia bilit y i n C V N 7 6 6 P K, or safet y  
P P D


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  1 0  of 4 6  
 
 
 
2. 3  
E n d p oi nts  
 
Pri m ar y  e n d p oi nt(s) 
T he  pri mar y e n d p oi nts of  t his st u d y will  be  t he f oll o wi n g: 
•  
P erce nta ge of  s u bjects w h o  e x perie nce  at least o ne  treat me nt-e mer ge nt  a d verse e ve nt ( T E A E) 
•  
P erce nta ge of  s u bjects wit h  a b n or mal a n d cli nicall y si g nifica nt ( C S) safet y la b orat or y test res ults 
at least o nce p ost -d ose  
•  
P erce nta ge of  s u bjects wit h  a b n or mal a n d C S electr ocar di o gra m  ( E C G) test res ults at least o nce 
p ost -d ose  
•  
P erce nta ge of  s u bjects wit h  a b n or mal a n d C S vital si g n  meas ure me nts  at least o nce  p ost  d ose  
 
Sec o n d ar y  e n d p oi nts(s) 
•  
Si n gle -d ose  plas ma  P K  para meters  of  C V N 7 6 6  i ncl u di n g  ti me  t o  ma xi m u m  plas ma  
c o nce ntrati o n  ( Tma x ), area u n der  t he plas ma  c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 2 4  ( A U C2 4) 
a n d ti me 0 t o i nfi nit y ( A U C i nf), a n d ter mi nal eli mi n ati o n half-life (t1/ 2z) M ulti ple-d ose plas ma 
P K para meters of C V N 7 6 6 i ncl u di n g C mi n , Ctr o u g h, Cma x , A U C fr o m ti me 0 t o t he e n d of d osi n g 
i nter val ( A U Ct), ter mi nal eli mi nati o n half-life (t1/ 2z), acc u m ulati o n rati o ( Racc), ti me t o stea d y- 
state ( Tss, ma x), stea d y-state Cma x ( Cma x,ss ), a n d stea d y-state Cmi n ( Cmi n,ss ) Si n gle -d ose  a n d m ulti ple - 
d ose C S F c o nce ntrati o ns a n d C S F: plas ma rati os of C V N 7 6 6  
 
Ot her  e n d p oi nts(s)  
•  
C ha n ge  fr o m baseli ne  i n safet y la b orat or y a n d E C G test res ults a n d vital  si g ns. 
•  
A d diti o nal  plas ma  P K  para meters  of  C V N 7 6 6:  C L/ F  or  C L/ Fss  a n d Vz/ F  or  Vz/ Fss  
 
2. 4  
S a m ple  Size  
Sa m ple size is  for me d b y a  t otal of 6 4 healt h y male a n d fe male s u bjects  1 8 t o  5 5  years ol d. I n S A D, u p 
t o 4 0 a d ult s u bjects. Fi ve c o h orts  ( C o h orts 1 t o 5) of  8 s u bjects eac h  ( 4 0 s u bjects i n t otal) will recei ve a 
si n gle d ose of C V N 7 6 6 or matc hi n g place b o orall y. 
I n M A D,  u p  t o 2 4  a d ult s u bjects. T hree c o h orts ( C o h orts 1 t o 3)  of  8 s u bjects eac h  ( 2 4 s u bjects i n t otal) 
will recei ve a dail y d ose of C V N 7 6 6 orall y.  
Si nce  t here  is  n o  f or mal  statistical  h y p ot hesis  testi n g,  n o  f or mal  sa m ple  size  calc ulati o n  has  bee n 
pe rf or me d.  T he  pr o p ose d  sa m ple  sizes  f or  eac h  st u d y  part  are  t y pical  f or  st u dies  at  t his  p hase  of 
de vel o p me nt a n d are dee me d s ufficie nt t o e val uate t he st u d y o bjecti ves f or t his P hase 1 st u d y.  
 
2. 5  
R a n d o miz ati o n  
I n S A D, fi ve c o h orts ( C o h orts 1 t o 5) of 8 s u bjects eac h ( 4 0 s u bjects i n total) will recei ve a si n gle d ose 
of C V N 7 6 6 or matc hi n g place b o. Wit hi n eac h c o h ort, 6 s u bjects will be ra n d o ml y assi g ne d t o recei ve 
C V N 7 6 6, a n d 2 s u bjects will recei ve matc hi n g place b o. F or eac h c o h ort, a se nti nel gr o u p of 2 s u bjects 
will i nitiall y be ra n d o mize d t o recei ve C V N 7 6 6 or place b o ( 1: 1 rati o) o n t he sa me da y t o all o w f or t he 
assess me nt  of  a n y ac ute a d verse e v e nts ( A Es). T he  re mai ni n g 6 s u bjects ( 5 C V N 7 6 6  a n d 1 place b o)  will 
be  ra n d o mize d a n d d ose d  at least 2 4  h o urs  after t he se nti nel gr o u p,  f oll o wi n g a re vie w of  a vaila ble safet y 
data b y t he S p o ns or a n d Pri nci pal I n vesti gat or ( PI).  
I n M A D,  t hree c o h orts ( C o h orts 1 t o 3)  of  8 s u bjects eac h ( 2 4 s u bjects i n t otal), will  be  e nr olle d. Wit hi n 
eac h c o h ort, 6 s u bjects will be ra n d o ml y assi g ne d t o recei ve C V N 7 6 6, a n d 2 s u bjects will recei v e 
matc hi n g place b o.  
P P D


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3. 
STATISTICAL CONSIDERATIONS 
Data will be handled and processed per the sponsor’s representative (Novotech) Standard Operating 
Procedures (SOPs), which are written based on the principles of good clinical practice (GCP). 
Each study part will be presented separately. 
 
3.1 
General Considerations 
All data collected on the electronic case report form (eCRF) will be presented in the data listings and 
will be listed and sorted by treatment arm, participant number and visit, where applicable. All descriptive 
summaries will be presented by treatment group and nominal visit/time point (where applicable). 
Unless otherwise stated, the following methods will be applied: 
• 
Continuous variables: Descriptive statistics will include the number of non-missing values (n), 
arithmetic mean, standard deviation (SD), median, minimum, and maximum values. 
The minimum and maximum values will be displayed to the same decimal precision as the source 
data, the arithmetic mean, SD, and median values will be displayed to one more decimal than the 
source data for the specific variable. 
The appropriate precision for derived variables will be determined based on the precision of the 
data on which the derivations are based, and statistics will be presented in accordance with the 
above-mentioned rules. 
• 
PK data: The actual blood sampling dates and times relative to dosing time will be listed by 
participant and nominal sampling time, with time deviation calculated, for all participants with 
available plasma concentration data, including participants excluded from the PK population. 
Individual (for each participant) and mean CVN766 concentrations over time will be displayed 
graphically in linear and semi-logarithmic plots of CVN766 concentrations versus time. The actual 
collection time will be used for individual plasma CVN766 concentration curves and the nominal 
time will be used for the plots of mean plasma CVN766 concentration curves. 
For PK concentration data, the number of non-missing values, number of below limit of 
quantification (BLQ) values, arithmetic mean, standard deviation, median, minimum, maximum, 
coefficient of variation (CV%), geometric mean and geometric coefficient of variation (geo CV%) 
values will be presented. For the calculation of summary statistics, unrounded data will be used 
and reported to three significant figures with the exception of n, n BLQ, and CV% which will be 
presented to the nearest integer and one decimal place, respectively. 
For PK parameter data, the number of non-missing values, arithmetic mean, standard deviation, 
median, minimum, maximum, coefficient of variation (CV%), geometric mean and geometric 
coefficient of variation (geo CV%) values will be presented. Individual PK parameters will be 
presented to three significant figures with the exception of λz which will be presented to four 
decimal places. 
• 
Categorical variables: Descriptive statistics will include counts and percentages per category. The 
denominator in all percentage calculations will be the number of participants in the relevant 
analysis population with non-missing data, unless specifically stated otherwise. Percentages will 
be displayed to one decimal place. Proportions will be displayed in 3 decimal places. 
• 
Repeat/unscheduled assessments: Only values collected at scheduled study visits/time points will 
be presented in summary tables. If a repeat assessment was performed, the result from the original 
assessment will be presented as the result at the specific visit/time point. All collected data will be 
included in the data listings. 
• 
Assessment windows: All assessments will be included in the data listings and no visit windows 
will be applied to exclude assessments that were performed outside of the protocol specified 
procedure windows. 


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• 
Result display convention: Results will be center aligned in all summary tables and listings. 
Participant identifiers visit and parameter labels may be left-aligned if required. 
• 
Date and time display conventions: The following display conventions will be applied in all 
outputs where dates and/or times are displayed: 
Date only: YYYY-MM-DD 
Date and time: YYYY-MM-DD HH:MM 
If only partial information is available, unknown components of the date or time will be presented as 
‘NK’ (not known), i.e., ‘2016-NK-NK’. Times will be reported in military time. 
 
3.2 
Key Definitions 
The following definitions will be used: 
• 
Baseline: The baseline value is defined as the last available valid (quantifiable continuous or 
categorical value), non-missing observation for each participant prior to first study drug 
administration. Repeat and unscheduled assessments will be included in the derivation of the 
baseline values. 
• 
Change from Baseline: The change from baseline value is defined as the difference between the 
result collected/derived at a post-baseline visit/time point and the baseline value. 
The change from baseline value at each post-baseline visit/time point will be calculated for all 
continuous parameters using the following formula: 
Change from Baseline Value = Result at Visit/Time Point – Baseline Value 
The change from baseline value will only be calculated if the specific post-baseline visit/time point 
result and the baseline value for the parameter are both available and will be treated as missing 
otherwise. 
• 
Study day: The study day of an event is defined as the relative day of the event starting with the 
date of the first study drug administration (reference date) as Day 1 (there will be no Day 0). 
The study day of events occurring before the first study drug administration will be calculated as: 
Study Day = (Date of Event - Date of First Study Drug Administration) 
For events occurring on or after Day 1, study day will be calculated as: 
Study Day = (Date of Event - Date of First Study Drug Administration) + 1 
Study days will only be calculated for events with complete dates and will be undefined for 
events that are ‘Ongoing’ at the end of the study. 
Relative days compared to an alternative reference point will be calculated similarly, but the 
alternative starting reference start date will be used instead of the date of the first study drug 
dosing. 
• 
Actual Time from First Dose (hours) = (Date/Time of PK Sample collection) – (Date/Time of 
First Dose on Day 1) 
• 
Actual Time from Last Dose (hours) = (Date/Time of PK Sample collection) – (Date/Time of Last 
Dose), where the last dose = Most Recent Previous Dose. 
• 
Actual Time Deviation (hours) = (Actual PK Sample Collection Time Post Dose) – (Scheduled 
PK Sample Collection Time Post Dose). 
• 
Prior Medications: Prior medications are defined as any medication where the use was stopped 
prior to the first administration of the study medication. 
• 
Concomitant Medications: Concomitant medications are defined as any medication (other than 
the study drug) that was used at least once after the first administration of the study drug. 


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Medications that were stopped on the same date as the first study drug administration will be 
defined as concomitant medications. If a clear determination cannot be made (partial medication 
end dates) the medication will be classified as concomitant 
• 
Treatment Emergent Adverse Events (TEAEs): are defined as adverse events that occurred within 
30 days (onset date – last date of dose + 1 ≤ 30) after study drug administration. 
 
 
3.3 
Inferential Analyses 
Descriptive statistics will be used to summarize the safety and PK data. No formal hypothesis testing is 
planned. 
All analyses (unless otherwise specified) will be performed at a two-sided 10% level of significance. 
• 
Dose Proportionality 
Dose proportionality will be evaluated for Cmax, AUCinf, AUCt, AUC24 (SAD) and steady state parameters 
AUCtau and Cmax,ss (MAD). Data will be presented graphically and a statistical analysis using the power 
model will be conducted. The analysis will be divided into days: 
SAD: Cmax, AUC24, AUCt, AUCinf 
MAD Day 1: Cmax, AUC24 
MAD Day 7: Cmax,ss, AUCtau. 
The model will include the loge-transformed CVN766 dose level as an independent variable. This model 
will be used to investigate the null hypothesis (H0: ß=1). Dose proportionality will be rejected (H1: ß 
not equal 1) if the 90% CI of the estimated slope falls outside the critical interval. 
The power model will have the form: 
Y = a*(dose)b 
where Y is the PK parameter, and a and b are the coefficient and exponent, respectively, of the power 
equation. 
By taking the natural logarithm (ln), the power model can be analyzed using linear regression and has 
the form: 
ln(Y) = ln(a)+b*ln(dose) + error =α + β*ln(dose) + error, 
where α is the intercept, and β is the slope, and ln(dose) is based on the dose size for each subject. 
Estimates of slope and intercept along with their 90% confidence intervals will be reported. A minimum 
of 3 values per dose must be available for a given parameter to estimate dose proportionality using the 
power model. For dose proportionality, the slope of the regression line (b) = 1 and for dose independence 
b = 0. 
Apparent dose linearity and proportionality of PK Parameters will be assessed graphically as well. The 
scatter plots and power model regression line will be plotted together with the natural log-transformed 
PK parameters as the values on the y-axis, and the natural log-transformed dose level as the values on 
the x-axis. Regression/scatter plot for SAD and MAD in the log-log scale for the Hummel power analysis 
will be performed by day. 
• 
Food Effect 
The effect of fed/fasting state on PK and bioavailability of CVN766 will be analyzed. The analysis will 
be descriptively. In addition, a random effects mixed model on the log-transformed pharmacokinetic 
parameters (AUCt, AUCinf, AUC24, and Cmax) will be applied to explore the effect of food, where meal 
status (fed vs. fasted) will be included as a fixed effect and participant will be included as a random 
effect. The geometric mean for fed/fasted and their 90% CIs will be estimated from the model based on 
the least squares means. The ratio of the geometric means (geometric mean ratio) and its 90% CI of the 


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fed data compared to the fasted data will be obtained based on the exponential of the difference of least- 
squares means (LSM) from the model. 
• 
Gender Effect 
The effect of gender (male vs. female) on Dose Normalized PK parameters of CVN766 will be analyzed. 
A random effects mixed model on the log-transformed pharmacokinetic parameters: 
SAD: Cmax/Dose, AUC24/Dose, AUCt/Dose, AUCinf/Dose and t1/2z 
MAD Day 1: AUC24/Dose, Cmax/Dose, AUCt/Dose, t1/2z and tmax. 
MAD Day 7: Cmax,ss/Dose, AUCtau/Dose, AUCt/Dose, t1/2z and tmax. 
will be applied to explore the effect of gender, where gender (male vs. female) will be included as a fixed 
effect and participant will be included as a random effect. The geometric mean for Male/Female and 
their 90% CIs will be estimated from the model based on the least squares means. The ratio of the 
geometric means (geometric mean ratio) and its 90% CI of the Male data compared to the Female data 
will be obtained based on the exponential of the difference of least-squares means (LSM) from the model. 
Point estimates and 90% CIs for differences on the log scale will be exponentiated to obtain estimates 
for the ratios of geometric means and respective 90% CIs on the original scale. 
For t1/2z, a non-parametric analysis (Hodges-Lehmann estimate) will be used to produce the median 
difference between female and male. A p-value will be generated by the Wilcoxon signed-rank test. 
 
3.4 
Multiple Comparisons and Multiplicity Adjustments. 
Not applicable for this study. 
 
3.5 
Handling of Missing Data 
For the classification of Treatment emergent adverse event (TEAE), Medical History and Concomitant 
medication, the following will be applied in the following order: 
a. 
If all dates/times (start and stop) missing, the event/medication will automatically be classified as 
a TEAE/Concomitant medication. 
b. 
For AEs with a missing start date/time, if the event end date/time is prior to first study drug 
administration, the event will not be classified as a TEAE. 
c. 
If only the AE start year/ medication end year is present and is the same or is after the first study 
drug administration year unit, the event/medication will be classified as a TEAE/Concomitant 
medication. 
d. 
If the AE start month and year/medication end month and year are present and are the same or 
after the first study drug administration month and year units, the event/medication will be 
classified as a TEAE/Concomitant medication. 
e. 
If start AEs, Concomitant Medication and Medical History Day is missing, it will be assigned as 
1st Day of the Month. If AEs, Concomitant Medication and Medical History Month is missing, it 
will be assigned as 1st Month of the Year and if AEs, Concomitant Medication and Medical History 
Year is missing, Informed Consent Year will be used. 
f. 
If end AEs, Concomitant Medication and Medical History Day is missing, it will be assigned as 
31st . If AEs, Concomitant Medication and Medical History Month is missing, it will be assigned 
as 12. 
For the PK analysis the following will be applied: 
a. 
For the concentration descriptive summaries, concentrations may be excluded if sampling time 
deviation is considered large to affect the profile at the discretion of the pharmacokineticist. 
b. 
Concentrations that are below limit of quantification (BLQ) prior to the first quantifiable value 
will be set equal to zero. Post dose BLQ concentrations, post Tmax, will be set to missing. 


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c. 
Where there are no results (NR), these will be set to missing. 
d. 
If more than 75% of values per nominal timepoint and treatment group are BLQ, then all 
descriptive statistics, except for nBLQ, will be denoted as not calculable (NC). 
e. 
For the calculation and graphical representation (semi-log and log-log plots) of geometric 
descriptive statistics, 0 values will be set to missing. 
f. 
For the purpose of calculating the non-compartmental PK parameters, concentrations that are BLQ 
prior to the first quantifiable value will be set equal to zero. BLQ values after measurable 
concentrations will be set to missing. Concentrations in the terminal phase, which is preceded by 
two BLQ values, will be set to zero. 
g. 
For the calculation of summary statistics of PK parameters, all NR and NC values in a data series 
will be set to missing. 


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Conversion of categorical values 
In some instances, continuous variables are expressed as a range (i.e., < 10). In such cases, values may 
be converted to the range boundary (upper or lower limit as applicable). As an example, a value of <10 
may be converted to 10. Such substitutions will be clearly documented in the footnotes of relevant 
outputs. 
 
3.6 
Coding of Events and Medications 
Medical history and AE verbatim terms will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) using the latest version available at the time of study commencement. Terms will 
be coded to the full MedDRA hierarchy, but the system organ class (SOC) and preferred terms (PT) will 
be of primary interest for the analysis. 
Prior and concomitant medications will be coded using the World Health Organization Drug Dictionary 
using the latest version available at the time of study commencement. Medications will be mapped to 
the full WHO-DD Anatomical Therapeutic Chemical (ATC) class level 4 and reported to class level 3 
and 4 hierarchy, but PTs will be of primary interest in this analysis. 
 
3.7 
Treatment Groups 
The following treatment group labels will be used for all summary outputs. 
Part 1 (SAD): 
This representation as below will only be used for the descriptive summary of concomitant medication, 
medical history and AEs and will not be based on feeding status: 
• 
S1: CVN766 5 mg 
• 
S2: CVN766 15 mg 
• 
S3 Fasted: CVN766 45 mg 
• 
S3 Fed: CVN766 45 mg 
• 
S4: CVN766 125 mg 
• 
S5 CVN766 250 mg 
• 
Overall CVN766 
• 
Overall Placebo 
• 
S3 Fed: Placebo 
• 
Overall 
Note: Overall CVN766 is the pooled group of all participants with active treatment. The assessments for 
the participants with active treatments in Cohort S3 Fed: CVN766 45 mg condition are not counted in 
‘Overall CVN766’, and they will be counted under ‘S3 Fed: CVN766 45 mg’. ‘Overall Placebo’ is the 
pooled group of all participants with placebo. The assessments for the participants with placebo in Cohort 
S3 fed condition are not counted in ‘All Placebo’, and they will be counted under ‘A3/Placebo/Fed’. In 
demographic and baseline characterises summary tables, Cohort S3 fed condition is not needed as 
appropriate. 
Part 2 (MAD): 
• 
M1: CVN766 45 mg 
• 
M2: CVN766 125 mg 
• 
M3: CVN766 250 mg 
• 
Overall CVN766 
• 
Overall Placebo 


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• 
Overall 
Note: Overall CVN766 is the pooled group of all participants with active treatment. 
Overall Placebo is the pooled group of all participants with placebo. 


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4. 
ANALYSIS SETS 
In this study 3 analysis populations are defined: Safety and PK. 
Furthermore, any additional exploratory analysis not identified in the SAP will be identified in the final 
CSR as exploratory post hoc analyses, including analyses for additional study populations or subgroups 
of interest. 
4.1 
Population Descriptions 
Safety Set 
The Safety Analysis Set will consist of all subjects who are enrolled and receive study drug. Subjects 
in this analysis set will be used for demographic, baseline characteristics, and safety summaries. 
 
PK Set 
The PK set will consist of all subjects who receive study drug and have at least 1 measurable plasma 
concentration. 
If any subjects are found to be non-compliant in dosing schedule or with incomplete data, a decision will 
be made on a case-by-case basis as to their inclusion in the analysis but will be presented in the subject 
listings. 


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5. 
PARTICIPANT DISPOSITION AND ANALYSIS POPULATIONS 
Participant disposition and analysis population analysis will be based on Safety population. Participant 
disposition and analysis populations will be summarized descriptively as described in section 3.1 
(categorical descriptive analysis). 
 
Participant Disposition 
Participant disposition will include the number of participants who completed the treatment/study as 
planned, participants withdrawn from the treatment /study, as well as the primary reason for early 
termination. Participant disposition will be summarized descriptively. 
 
Analysis Populations 
The number of participants included in each study populations will be summarized descriptively. 
In addition, the inclusion of each participant into/from each of the defined analysis populations will be 
presented in the by-participant data listings. 


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6. 
PROTOCOL DEVIATIONS 
Protocol deviations will be presented for each participant in the by-participant data listings, sorted by 
study part, dose level and participant ID based on the All-Enrolled population. 
Prior to database lock, all protocol deviations will be reviewed by medical monitors and assigned a status 
of importance if qualifying as such. 
Protocol deviations, including Minor and Important protocol deviations, will be categorized as noted in 
the Protocol deviation management plan version 4.0 amendment 3 dated 19 May 2022. 
All protocol violations that impact the safety of the patients and/or the conduct of the study and/or its 
evaluation will be reported. These include: 
• 
Patients who are dosed on the study despite not satisfying the inclusion criteria 
• 
Patients who develop withdrawal criteria whilst on the study but are not withdrawn 
• 
Patients who receive the wrong treatment or an incorrect dose 
• 
Patients who receive an excluded concomitant medication 
• 
Deviations from GCP. 
The identification of these and other CSR-reportable deviations will be based on the inclusion/exclusion 
criteria or other criteria presented in the protocol. 


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7. 
DEMOGRAPHIC AND BASELINE INFORMATION 
Demographic and baseline information analysis will be based on Safety population. Demographic and 
baseline information will be summarized descriptively as described in section 3.1. 
 
7.1 
Demographics 
The following demographic parameters will be analyzed: 
Continuous descriptive analysis: 
• 
Age (years) 
• 
Height (cm) 
• 
Weight (kg) 
• 
BMI (kg/m2) 
Categorical descriptive analysis: 
• 
Sex 
• 
Childbearing Potential 
• 
Race 
• 
Ethnicity 
 
7.2 
Medical /Surgical history 
Medical / Surgical history will be coded using MedDRA® and will be presented in the by-participant 
data listings. Medical history to be obtained will include determining whether the subject has any 
significant conditions or diseases that stopped at or prior to signing the ICF. 
 
7.3 
Hepatitis panel and HIV Antibody Test 
Hepatitis B Antigen (HBsAg), Hepatitis C Antibody (HCVAb), and Human Immunodeficiency Virus 
(HIV-1/HIV-2 Antibody) results will be presented in the by-participant data listings. 
 
7.4 
Alcohol, Urine Drug & Cotinine Screen Test 
Urine Drug Test results will be presented in the by-participant data listings. 
 
7.5 
Follicle stimulating hormone (FSH) Test 
FSH Test results will be presented in the data listings. 
 
7.6 
Pregnancy Test (Serum and Urine) 
Serum and urine pregnancy test results will be presented in the by-participant data listings. 


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8. 
TREATMENT EXPOSURE 
All study drug administration information (study drug administered (Yes/No), reason not administered, 
dose administered (mg), date and time of administration, vomiting (Yes/No), lot number/ bottle Number 
and date/time of first/last meal will be presented in the by-participant data listings under the Safety Set. 


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9. 
PRIOR AND CONCOMITANT MEDICATIONS 
Concomitant medications will be coded using the most current version of the World Health Organization 
Drug Dictionary (WHO-DD) and summarized by Anatomical Therapeutic Chemical (ATC) class Level 
3 and PT and will be presented alphabetically as noted in section 3.1 (categorical descriptive analysis) 
using Safety Set. All concomitant treatments, blood products, as well as nondrug interventions received 
by patients from screening until the end of study visit will be recorded on the eCRF. 
The number and percentage of subjects using at least one concomitant medication will be displayed 
together with the number and percentage of subjects using at least one medication within each therapeutic 
class (ATC-Level 3) and preferred name A participant who used the same medication on multiple 
occasions will only be counted once in the specific category (PT). These will be summarized under the 
Safety population for dose levels defined in section 3.5 Prior medications will be presented in the by- 
participant data listings. 
For food effect cohort, a concomitant medication starting in period 1 (Fasted) and continuing into the 
next period (Fed) is counted only in the onset period. 


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  2 4  of 4 6  
 
 
 
1 0.  
P H A R M A C O KI N E TI C S  
 
1 0. 1  
C ollecti o n  of  Pl as m a/ Ser u m  S a m ples  f or P K  A n al ysis  S A D  
All  P K  a nal yses,  s u m mar y  ta bles  a n d  fi g ures  will  be  base d  o n  t he  P K  set.  All  a nal yses  will  be  
s um marize d  as descri be d  i n secti o n 3. 1  ( P K - c o nti n u o us descri pti ve  a nal ysis).  All  listi n gs will  be  base d 
o n t he Safet y set e xce pt f or t he P K para meter listi n gs.  
F or S A D ( Part 1, C o h orts 1, 2, 3a, 4, 5 a n d C o h ort 3 F E), bl o o d sa m ples will be c ollecte d at Pre -d ose 
( wit hi n 1 5  mi n utes  pri or  t o d osi n g)  a n d at 0. 5, 1,  1. 5,  2,  3,  5,  8,  1 2,  1 6,  2 4 -, 3 6 -, 4 8 -, a n d 7 2 -h o urs  p ost - 
d ose. A bl o o d sa m ple will be c ollecte d pri or t o disc har ge i n case of earl y ter mi n ati o n.  
 
 
 
 
 
 
 
1 0. 2  
C ollecti o n  of  Pl as m a/ Ser u m  S a m ples  f or P K  A n al ysis  M A D  
F or  M A D  ( Part 2), bl o o d  sa m ples will  be  c ollecte d as f oll o ws: Da y  1:  Pre-d ose  ( wit hi n 1 5  mi n utes  pri or 
t o d osi n g) a n d at 0. 5, 1, 1. 5, 2, 3, 5, 8, 1 2, 1 6, a n d 2 4 ( Da y 2 pre-d ose) h o urs p ost -d ose. Da y 3, Da y 4, 
Da y 5, a n d Da y 6: Pre -d ose ( wit hi n 1 5 mi n utes pri or t o d osi n g). Da y 7: Pre -d ose ( wit hi n 1 5 mi n utes 
pri or t o d osi n g) a n d at 0. 5, 1, 1. 5, 2, 3, 5, 8, 1 2, 1 6, 2 4, 3 6, 4 8, a n d 7 2 (a) h o urs p ost -d ose. A bl o o d 
sa m ple will b e c ollecte d pri or t o disc har ge i n case of earl y ter mi nati o n. 
 
 
 
 
 
 
P P D


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  2 5  of 4 6  
 
 
 
 
 
 
 
 
 
 
 
 
1 0. 5  
P h ar m ac o ki netic  P ar a meters 
P art 1 – Si n gle Asce n di n g D oses  
T he  foll o wi n g  p har mac o ki netic  para meters  will,  w here  p ossi ble,  be  deter mi ne d   fr o m t he plas ma 
c o nce ntrati o ns a n d C S F of  a nal yte usi n g  n o n -c o m part me ntal  met h o ds  via  P h oe ni x  Wi n N o nli n  Versi o n  
8. 3 or hi g her . 
P art  1 – Si n gle  Asce n di n g  D ose  
 
P ar a meter  
Defi niti o n  
C ma x  
O bser ve d  ma xi m u m  C V N 7 6 6  c o nce ntrati o n  w hic h  is directl y  deter mi ne d  fr o m t he 
plas ma  c o nce ntrati o n  ti me pr ofiles  
T ma x  
Ti me  t o o bser ve d  ma xi m u m  o bser ve d  C V N 7 6 6  c o nce ntrati o n.  If t he sa me C ma x  
c o nce ntrati o n  occ urs  at differe nt ti me p oi nts,  Tma x  is assi g ne d  t o t he first 
occ urre nce of C ma x . 
T last 
Ti me  t o last o bser ve d  C V N 7 6 6  c o nce ntrati o n. 
A U C 2 4  
T he  area u n der  t he plas ma  C V N 7 6 6  c o nce ntrati o n -ti me c ur ve, fr o m ti me 0  (ti me 
of  d osi n g)  t o 2 4  h o urs,  calc ulate d  b y  li near tra pez oi dal/ li near i nter p olati o n 
met h o d  
A U C t 
Area  u n der  t he dr u g  c o nce ntrati o n -ti me c ur ve, fr o m ti me 0  (ti me of  d osi n g)  t o t he 
last meas ura ble  c o nce ntrati o n  usi n g  li near tra pez oi dal/ li near i nter p olati o n met h o d  
A U C i nf 
T he area u n der t he plas ma C V N 7 6 6 c o nce ntrati o n -ti me c ur ve fr o m ti me 0 (ti me 
of  d osi n g)  e xtra p olate d  t o i nfi nit y. A U C i nf is calc ulate d  as t he s u m of  A U C t pl us  
t he rati o of  t he last meas ura ble  plas ma  c o nce ntrati o n  ( Clast) t o t he eli mi nati o n rate 
c o nsta nt ( λ z), calc ulate d b y li near tra pez oi dal/ li near i nter p olati o n met h o d. 
A U C %e xtra p  
T he  perce nta ge  of  t he A U C  t hat has  bee n  e xtra p olate d be y o n d  t he last 
o bser ve d data p oi nt, usi n g t he f oll o wi n g f or m ula, calc ulate d b y li near 
tra pez oi dal/ li near i nter p olati o n met h o d 
A U C %e xtra p = ( A U Ci nf - A U C t/( A U Ci nf) * 1 0 0 
λ z 
A p pare nt  ter mi nal eli mi nati o n rate c o nsta nt calc ulate d  b y  li near re gressi o n of  t he 
ter mi nal li near p orti o n  of  t he l o g c o nce ntrati o n  vs.  ti me c ur ve. 
t½ 
A p pare nt  plas ma  ter mi nal half -life calc ulate d as  l n ( 2)/ λz 
C L/ F  
A p pare nt  t otal plas ma  cleara nce, usi n g  t he f oll o wi n g f or m ula 
D ose/ A U C i nf. 
V z/F  
A p pare nt  v ol u me  of  distri b uti o n  base d  o n  t he ter mi nal p hase,  re p orte d t o 
3 si g nifica nt fi g ures a n d calc ulate d  as: D ose/( λ z× A U C i nf). 
C S F: Plas ma 
rati o 
Rati o  of  t he C V N 7 6 6  c o nce ntrati o n  i n C S F  vs.  t he C V N 7 6 6  c o nce ntrati o n  i n 
plas ma at 3 h p ost d ose.  
D N _ C ma x  
D ose -n or malize d  C ma x = C ma x/ d ose  
D N _ A U C 2 4 hr  
D ose -n or malize d  A U C 2 4 hr  =  A U C 2 4 hr/ d ose 
D N _ A U C t 
D ose -n or malize d  A U C t =  A U C t/ d ose 
P P D


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DN_AUCinf 
Dose-normalized AUCinf = AUCinf/dose 
 
 
 
Part 2 – Multiple Ascending Doses 
All PK analyses, PK summary tables and figures will be based on the PK set. All analyses will be 
summarized as described in section 3.1 (PK - continuous descriptive analysis). All listings will be based 
on the PK set. All missing and BLQ handling of urine concentrations for PK analysis will be based on 
section 3.5. 
Approximate attainment of steady state will be visually assessed by plotting mean Ctrough concentrations. 
The following pharmacokinetic parameters will, where possible, be determined from the plasma 
concentrations and CSF of analyte using non-compartmental methods via Phoenix WinNonlin Version 
8.3 or higher. 
 
 
Parameter at 
Day 1 
Definition 
Cmax 
Observed maximum CVN766 concentration in the dosing interval at Day 1 
Cmin, 
Observed minimum CVN766 concentration in the dosing interval at Day 1 
Ctrough DayN 
Plasma concentration at the end of the dosing interval at day N, where N is Day 
2,3,4,5,6,or 7 
Tmax 
Time to reach maximum CVN766 concentration at Day 1 
Tmin 
Time of minimum observed CVN766 concentration at Day 1 
AUCt 
Area under the drug concentration-time curve, from time 0 (time of dosing) to the 
last measurable concentration at steady state using ‘linear trapezoidal/ linear 
interpolation method’ when t is < 24h. Determined following Dose on Day 7 
AUC24 
The area under the plasma CVN766 concentration-time curve, from time 0 
to 24 hours, calculated by linear trapezoidal/ linear interpolation method. 
Determined following Dose on Day 1 
CSF:Plasma 
ratio: 
Ratio of the CVN766 concentration in CSF vs the CVN766 concentration in 
plasma at 3 h post dose 
DN_Cmax,ss 
Dose-normalized Cmax,ss = Cmax,ss/dose 
DN_AUC24hr 
Dose-normalized AUC24hr = AUC24hr/dose 
DN_AUCt 
Dose-normalized AUCt = AUCt/dose 


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Parameter at 
Day 7 
Definition 
Cmax, ss 
Observed maximum CVN766 concentration in the dosing interval at steady state 
at Day 7. 
Cmin,ss 
Observed minimum CVN766 concentration in the dosing interval at steady state 
at Day 7. 
Ctrough DayN 
Plasma concentration at the end of the dosing interval at day N, where N is Day 
2,3,4,5,6,or 7 
Cavg,ss 
Average steady state CVN766 concentration, determined following Dose on Day 
7, using the following formula 
Cavg,ss = AUCtau/ tau 
Where, tau = dosing interval 
Tmax, ss 
Time to reach maximum CVN766 concentration in the dosing interval at steady 
state at Day 7. 
Tmin, ss 
Time of minimum observed CVN766 concentration in the dosing interval at 
steady state at Day 7. 
Tlast, ss 
Time of the last CVN766 concentration assessment in the dosing interval at 
steady state. Determined following Dose on Day 7 
AUCt 
Area under the drug concentration-time curve, from time 0 (time of dosing) to the 
last measurable concentration at steady state using ‘linear trapezoidal/ linear 
interpolation method’ when t is < 24h. Determined following Dose on Day 7 
AUCtau 
Area under the plasma CVN766 concentration-time curve over a dosing interval 
at steady state using the linear trapezoidal/ linear interpolation method. 
Determined following Dose on Day 7 
AUCinf 
The area under the plasma CVN766 concentration-time curve from time 0 (time 
of dosing) extrapolated to infinity. AUCinf is calculated as the sum of AUCt plus 
the ratio of the last measurable plasma concentration (Clast) to the elimination rate 
constant (λz), calculated by linear trapezoidal/ linear interpolation method. 
Determined following dose on Day 1 
λz or Kel 
Apparent terminal elimination rate constant calculated by linear regression of the 
terminal linear portion of the log concentration vs. time curve. Determined 
following Dose on Day 7 
t½ 
Apparent plasma terminal half-life calculated as ln (2)/λz.. Determined following 
Dose on Day 1 and Day 7 
CL/Fss 
Apparent total plasma clearance at steady state, using the following formula 
Dose/AUCtau. Determined following Dose on Day 7 
Vz/Fss 
Apparent terminal volume of distribution, calculated as: Dose/ (λz × AUC0-tau). 
Determined following Dose on Day 7 
RACmax 
Accumulation ratio based on Cmax in Part 2 calculated as Cmax,ss on Day 7/Cmax on 
Day 1 for each individual. 
RAAUC 
Ratio of the measure of systemic drug exposure over a specific dosing interval at 
steady state to the measure of systemic drug exposure over a specific dosing 
interval after single dose administration. It is calculated as AUCtau Day 7/AUC24 Day 1 
CSF:Plasma 
ratio: 
Ratio of the CVN766 concentration in CSF vs the CVN766 concentration in 
plasma at 3 h post dose 
DN_Cmax,ss 
Dose-normalized Cmax,ss = Cmax,ss/dose 
DN_AUCt 
Dose-normalized AUCt = AUCt/dose 
DN_AUCtau 
Dose-normalized AUCtau = AUCtau/dose 
DN_AUCinf 
Dose-normalized AUCinf = AUCinf/dose 
 
Ctrough determination for MAD cohorts: 


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Ctrough_Day1 
The pre-dose morning concentration observed on day 2 prior to the next dosing 
Ctrough_Day2 
The pre-dose morning concentration observed on day 3 prior to the next dosing 
Ctrough_Day3 
The pre-dose morning concentration observed on day 4 prior to the next dosing 
Ctrough_Day4 
The pre-dose morning concentration observed on day 5 prior to the next dosing 
Ctrough_Day5 
The pre-dose morning concentration observed on day 6 prior to the next dosing 
Ctrough_Day6 
The pre-dose morning concentration observed on day 7 prior to the next dosing 
 
Ctrough_Day1, Ctrough_Day2, Ctrough_Day3, Ctrough_Day4, Ctrough_Day5, Ctrough_Day6 will be listed for each MAD cohort and 
dose level. 
Additional pharmacokinetic parameters may be determined where appropriate. 
Pharmacokinetic analysis will be carried out using actual doses and blood sampling times (post dose 
hourly sampling times for the specified days), where possible. If actual times are missing, nominal times 
may be used with sponsor approval. 
Plasma, urine, and CSF concentrations of CVN766 will be used as supplied by the bioanalytical 
laboratory. The units of concentration and resulting PK parameters, with amount or concentration in the 
unit, will be presented as they are received from the bioanalytical laboratory. 
If a PK parameter cannot be derived from a patient’s concentration data, the parameter will be coded as 
NC (i.e., not calculated). NC values will not be generated beyond the day that a patient discontinues. If 
an individual patient has a known biased estimate of a PK parameter (due for example to a deviation 
from the assigned dose level and/or concomitant medication violation), this will be footnoted in summary 
tables and the parameter will not be included in the calculation of summary statistics or statistical 
analyses. 
Pharmacokinetic Noncompartmental Analysis (NCA) 
General Plasma NCA Pharmacokinetic Settings 
The general settings in Phoenix WinNonlin® for generation of plasma PK parameters are as listed below. 
• 
NCA Model Type: 
Plasma (200-202) 
• 
Weighting: 
Uniform 
• 
AUC Calculation Method: 
Linear trapezoidal/ linear interpolation method 
• 
Dose Options Type: 
Extravascular 
• 
Slopes Setting Fit Method: 
Best Fit/Visual Inspection 
• 
Rsq_Adjusted Criteria for ‘λz’: 
0.8 
• 
AUC% extrapolation Criteria: 
20 
10.6 
Urine PK Parameters MAD 
All PK summary tables and figures will be based on the PK population. All analyses will be summarized 
as described in section 3.1 (PK - continuous descriptive analysis). All listings will be based on the safety 
population. All missing and BLQ handling of urine concentrations for PK analysis will be based on 
section 3.5. 
Pharmacokinetic analysis will be carried out using actual doses, actual urine sampling times (start and 
end times), actual urine volumes, where possible. If actual times are missing, nominal times may be used 


Pr ot oc ol  N u m ber:  C V N 7 6 6 -1 0 1  
D oc u me nt  stat us: V ersi o n  1. 0  
2 0 2 2 -1 0 -2 0  
N o v otec h  - Strictl y  C o nfi de ntial  
Pa ge  2 9  of 4 6  
 
 
 
wit h  s p o ns or  a p pr o val.  T he  f oll o wi n g  uri ne  p har mac o ki netic  para meters  will,  w here  p ossi ble,  be  
deter mi ne d fr o m t he uri ne c o nce ntrati o ns of C V N 7 6 6 a n d t he res pecti ve uri ne v ol u mes wit hi n eac h 
c ollecti o n i nter val b y n o n -c o m part me ntal met h o d usi n g P h oe ni x Wi n N o nli n s oft ware ( Versi o n 8. 3 or 
hi g her, Certara, U S A):  
N ote: P K  uri ne sa m ples a n d uri ne v ol u mes will be c ollecte d at t he f oll o wi n g ti me p oi nts ( ± 1 5 mi n utes) 
o n  Da y  1:  0 t o 6,  6 t o 1 2,  a n d 1 2  t o 2 4  h o urs  p ost  d ose  f or M A D  a n d o n  Da ys  7:  0 t o 6,  6 t o 1 2  a n d 1 2  t o 
2 4  h o urs  f or M A D  C o h ort  1.  
 
P K  c o nce ntrati o n  a n d para meter  data  will  be  a nal yze d  descri pti vel y  as n ote d  i n secti o n 3. 1 . 
 
Ge ner al  Uri ne  N C A  P h ar m ac o ki netic  Setti n gs  
T he  ge neral  setti n gs i n P h oe ni x  Wi n N o nli n ®  f or ge nerati o n  of  uri ne  P K  para meters  are as liste d bel o w.  
•  
N C A  M o de l T y pe:  
Uri ne  ( 2 1 0-2 1 2)  
•  
Wei g hti n g:  
U ni f or m 
•  
A U C  Calc ulati o n  Met h o d  (if a p plica ble):  Li near  tra pez oi dal/ li near i nter p olati o n met h o d  
 
1 0. 7  
Criteri a  f or t he C alc ul ati o n  of  a n  A p p are nt  Ter mi n al  Eli mi n ati o n  H alf -Life  
T he start of t he ter mi nal eli mi nati o n p hase f or eac h partici pa nt will be defi ne d b y vis ual i ns pecti o n a n d 
will ge nerall y be t he first p oi nt at w hic h t here is n o s yste matic de viati o n fr o m t he l o g li near decli ne i n 
plas ma c o nce ntrati o ns.  
N u m ber  of  D at a  P o i nts 
 
At  least 3 d ata p oi nts  will  be  i ncl u de d i n t he re gressi o n a nal ysis a n d n ot  i ncl u di n g Cma x . T he  n u m ber  of 
p oi nts a n d t he be gi n ni n g a n d e n d ti mes of t he ter mi nal p hase will be liste d f or eac h i n di vi d ual.  
 
Pl a usi bilit y  
 
T he  data  will  be  p har mac o ki neticall y  pla usi ble.  
 
S u m m ar y  of  Pl as m a  / Uri ne  P K  C o nce ntr ati o ns  a n d  P K  P ar a meters  
Plas ma P K (c o nce ntrati o n a n d P K para meters Ae t 1-t 2, Fet 1-t 2, a n d C Lr) data f or Part 1 ( S A D) a n d Part 2 
( M A D)  will  be  s u m marize d  se paratel y.  All  P K  s u m mar y  ta bles  a n d  fi g ures  will  be  base d  o n  t he  P K 
p o p ulati o n,  a n d  P K  listi n gs  will  be  base d  o n  P K  p o p ulati o n.  All  a nal yses  will  be  s u m marize d 
descri pti vel y i n ge neral acc or di n g t o secti o n 3. 1  
P P D


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The actual blood sampling dates and times relative to dosing time will be listed by participant and 
nominal sampling time, with time deviation calculated, for all participants with available plasma 
concentration data, including participants excluded from the PK population. Individual values for PK 
concentration data will be reported to the same level of precision as received from the bioanalytical 
laboratory. 
 
Summary of PK concentrations 
 
For the concentration-time data/profile summary, the following will be applied: 
• 
For the concentration descriptive summaries, concentrations may be excluded if sampling time 
deviation is considered too large to affect the profile at the discretion of the pharmacokineticist. 
• 
Concentrations that are below limit of quantification (BLQ) will be set to 0 for the calculation of 
standard statistics (i.e. arithmetic mean) and set to missing for the calculation of geometric statistics. 
For PK parameters, all plasma concentrations will be set to BLQ if prior to first measurable 
concentration and treated as missing thereafter 
 
Individual (for each participant) and mean (SD) concentrations over time for the analyte will be displayed 
graphically in linear and semi-logarithmic plots of the analyte concentrations versus time. The actual 
collection time will be used for individual plasma analyte concentration curves, and the nominal time 
will be used for the plots of mean plasma analyte concentration curves. 
 
Summary of Plasma PK parameters 
 
PK parameters will be determined for each analyte with intensive PK samplings. For the purpose of 
calculating the non-compartmental PK parameters, concentrations that are BLQ prior to the first 
measurable concentration value will be set equal to zero. BLQ values embedded between measurable 
concentrations will be set to missing. Concentrations that are BLQ in the terminal phase after the last 
measurable concentration will be set to missing. 
It should be noted the imputation of BLQ for the determination of PK parameters is different from the 
BLQ imputation when PK concentrations are summarized. When PK parameters are estimated by a 
standard non-compartmental model, actual collection time will be used in the calculation of plasma PK 
parameters. 
 
 
Goodness of Fit 
 
• 
If data permits, the default ‘best fit’ method by Phoenix WinNonlin will be used for the 
selection of slopes to determine ‘λz’. If data do not permit, then the slope selection will be done 
by visual inspection or by a manual method to determine λz. 
• 
When assessing terminal elimination phases, the R2 adjusted value will be used as a measure of 
the goodness of fit of the data points to the determined line. 
• 
Regression-based parameters (λz or kel, AUCinf, AUC%extrap, t1/2, CL/F or CL/Fss, and Vz/F or 
Vz/Fss) will only be calculated if the R2 adjusted value of the regression line is greater than or 
equal to 0.8 If regression-based parameters cannot be calculated, they will be set to “NC”, 
defined as “not calculated” in the data listings and summary tables as appropriate. 
 
Calculation of AUC 
 
• 
The minimum requirement for the calculation of AUC will be the inclusion of at least 3 
consecutive plasma concentrations above the lower limit of quantification (LLOQ), with at 
least one of these concentrations following Cmax. 
• 
All AUC values will be calculated using linear trapezoidal/ linear interpolation method 
 
Period of Estimation 


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• 
Time period used for the estimation of t1/2, where possible, will be over at least 2 half lives. 
• 
Where an elimination half-life is estimated over a time period of less than 2 half-lives, it will be 
flagged in the data listings at the discretion of the pharmacokineticist, and the robustness of the 
half-life value and regression-based parameters (λz or kel, AUCinf, AUC%extrap, t1/2, CL/F or 
CL/Fss, and Vz/F or Vz/Fss) should be discussed in the study report. 
 
Inferential Analyses 
The following endpoints will be analyzed as described in sections 3.3: 
• 
Dose proportionality 
o Dose proportionality - CVN766 SAD 
 
AUCinf 
 
AUCt 
 
AUC24 
 
Cmax 
o Dose proportionality - CVN766 MAD 
 
MAD Day 1: Cmax, AUC24 
 
MAD Day 7: Cmax,ss, AUCtau. 
• 
Food-Effect Assessment (SAD: Cohort S3): 
The following parameters will be analyzed as described in sections 3.3: 
o AUCt 
o AUCinf 
o AUC24 
o Cmax 
• 
Gender effect Assessment 
The following parameters will be analyzed as described in sections 3.3: 
SAD : Cmax/Dose, AUC24/Dose, AUCt/Dose, AUCinf/Dose, Tmax and t1/2z. 
MAD Day 1: AUC24/Dose, Cmax/Dose, AUCt/Dose, t1/2z and tmax. 
MAD Day 7: Cmax,ss/Dose, AUCtau/Dose, AUCt/Dose, t1/2z and tmax. 
Details are provided in section 3.3 of SAP. 


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11. 
SAFETY 
Safety endpoints will be analyzed using the Safety population and will be summarized descriptively as 
described in section Error! Reference source not found.. Safety data will be summarized separately 
for Part 1 (SAD) and Part 2(MAD). 
 
11.1 
Adverse Events 
All AEs including will be coded using latest MedDRA version. All AE summaries will be restricted to 
TEAEs only. AEs will be grouped by system organ class (SOC) and preferred term (PT) and 
summarized, by actual treatment group and overall. Summary tables will include the number of 
participants (%) experiencing an event and the number of events. Participants will be counted only once 
for each SOC and PT level; they will be sorted alphabetically and for PT tables only, they will be ordered 
with the highest first (categorical descriptive analysis). 
For food effect cohort, an adverse event starting in one period and continuing into the next period is 
counted only in the onset period. 
 
Assigned treatment 
Definition 
Treatment Period 1 
(Fasting) 
AE start date/time is on or after the dose date/time of treatment received in 
Period 1 and prior to the date/time of treatment received in period 2 (fed 
period) no matter when AE stops. 
Treatment Period 2 
(Fed) 
AE start date/time is on or after the dose date/time of treatment received in 
Period 2 until the end of study. 
 
For Part 1 (SAD) Cohort S3 food effect arm, TEAE will be further assigned to S3/Fasted (period 1) or 
S3/Fed (period 2) by using period 2 start date and TEAE’s that start post first study drug administration 
of period 2 (Fed) will not be attributed to treatment during period 1 (Fasted). TEAE’s that start post first 
study drug administration of period 1, but prior to first study drug administration of period 2, will be 
attributed to period 1 only. TEAEs that start post first study drug administration of period 1 (Fasted) and 
ongoing will be attributed to Onset period only 
The TEAE summaries will include: 
• 
Overall summary of TEAEs. 
• 
TEAE summary by SOC and PT. 
• 
TEAE summary of serious events by SOC and PT. 
• 
TEAE summary by SOC, PT and Severity. 
• 
TEAE summary by SOC, PT and relationship to study drug. 
• 
TEAE summary of events leading to the study drug discontinuation by SOC and PT. 
• 
Overall Frequency of TEAE by PT. 
• 
Overall Frequency of related TEAE by PT. 
 
11.2 
Safety Laboratory Assessments 
Blood and urine samples will be collected at the time points specified in the Schedule of Events (refer to 
the Protocol) to conduct hematology, chemistry, and urinalysis (including microscopic examinations) 
analyses. Clinical laboratory data will be summarized by the type of laboratory test. The number and 
percentage of subjects who experience abnormal (i.e., outside of reference ranges) and/or clinically 
significant abnormalities after study drug administration will be presented for each clinical laboratory 


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measurement. For each clinical laboratory measurement, descriptive statistics will be provided for 
baseline and all subsequent post-treatment scheduled visits. 
Changes from baseline to the post-treatment visits will also be provided. Descriptive statistics of vital 
signs will also be provided in a similar manner. In addition, shift from baseline in CTCAE grade (where 
applicable) and by high/low flags (where CTCAE grades are not defined) will be presented by dose level. 
The following tests will be performed within each of the specified test panels: 
 
Hematology: 
Serum Chemistry: 
Urinalysis & Microscopic 
Urinalysis: 
• 
RBC (x1012/L) 
• 
ALT (U/L) 
• 
pH (4.5-8) 
• 
WBC with differential (% and 
absolute; x109/L) 
• 
Albumin (g/L) 
• 
Specific gravity 
(1.002-1.030) 
• 
Hemoglobin (g/L) 
• 
Alkaline 
phosphatase 
(U/L) 
• 
Protein (g/L) 
• 
Hematocrit (L/L) 
• 
Lipase (U/L) 
• 
Glucose 
(mmol/L) 
• 
Platelets (x109/L) 
• 
AST (U/L) 
• 
Blood 
• 
PT/INR 
• 
Total bilirubin 
(umol/L) 
• 
Nitrite 
 
• 
Direct bilirubin 
(umol/L) 
• 
Microscopic 
Analysis (only if 
positive dipstick 
results): 
 
• 
Total protein 
(g/L) 
• 
RBC/high power 
field 
 
• 
Creatinine 
(umol/L) 
• 
WBC/high power 
field 
 
• 
BUN/Urea 
(mmol/L) 
• 
Epithelial cells, 
casts etc 
 
• 
Creatine kinase 
(U/L) 
 
 
• 
GGT (U/L) 
 
 
• 
Potassium 
(mmol/L) 
 
 
• 
Sodium 
(mmol/L) 
 
 
• 
Glucose 
(mmol/L) 
 
 
• 
Chloride 
(mmol/L) 
 
 
• 
Bicarbonate 
(mmol/L) 
 


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• 
Calcium 
(mmol/L) 
 
 
All laboratory data collected at scheduled and unscheduled visits will be included in the listings, but only 
results collected as scheduled visits will be included in the summary tables. 
If required, the results (and the corresponding normal range cut-off values) for individual parameters 
may be converted to International System of Units (S.I.) units to summarize the data. 
For all the parameters where a unit value has been reported, the parameter names that will be used in the 
outputs will comprise of the test name and the unit of measure, for example, ‘Albumin (g/L)’. For the 
urinalysis parameters, the parameter name will be the reported test name only. Parameters will be sorted 
alphabetically within tables and listings. 
For all parameters where a normal range limit value was reported, the normal range will be derived based 
on the available lower and upper limit values and any reported mathematical symbols. If both a lower 
and upper limit value is available, the normal range will be presented as ‘(Lower, Upper)’. 
The reported results for each parameter with a defined normal range will be classified (‘Low’, ‘Normal’, 
‘High’) in relation to the defined normal range limits. If a result is equal to the normal range cut-off 
value, the result will be considered ‘Normal’. 
The hematology and chemistry results tables will present summary statistics for each laboratory 
parameter within the specific test panel. For each parameter, summaries will be presented for the baseline 
and each scheduled post-baseline visit. In addition, summaries will be presented for the change from 
baseline values at each scheduled post-baseline visit (continuous descriptive analysis). 
In particular, quantitative data will be summarized using simple descriptive statistics (mean, SD, median, 
minimum, and maximum) of actual values and changes from baseline for each nominal visit over time. 
The changes computed will be the differences from baseline. Qualitative data based on reference ranges 
will be described according to the categories (i.e., Low, Normal, High). 
The decimal precision to which the summaries for each parameter will be based on the maximum number 
of decimals to which the reported result or the normal range limits are presented to in the raw data. The 
results and normal ranges will be displayed to the same decimal precision in the listings. 
Additionally, counts (%) of number participants with values out of normal range at each scheduled time 
point will also be presented along with shift tables that will represent the changes in normal range 
categories across post-baseline time points (categorical descriptive analysis). 
The urinalysis table will present counts and percentages of normal, abnormal clinically significant and 
clinically significant for the reported results at baseline and each post-baseline visit for all parameters 
(categorical descriptive analysis). 
 
11.3 
Vital Signs 
The following vital signs measurements will be taken at the time points specified in the Schedule of 
Events (refer to the Protocol): 
• 
Pulse (beats/min); 
• 
Systolic Blood Pressure (SBP) (mmHg) 
• 
Diastolic Blood Pressure (DBP) (mmHg) 
• 
Respiratory Rate (breaths/min) 
• 
Body Temperature (ºC) 
All vital signs data collected at scheduled and unscheduled visits will be included in the listings, but only 
results collected as scheduled visits will be included in the summary tables. 
Triplicate orthostatic vital signs (blood pressure and heart rate) will be recorded at baseline (Check-in 
Day -1) 15 minutes apart (the average will be used to determine eligibility). 


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The parameter names that will be used in the outputs will comprise of the test name and the unit of 
measure, for example, ‘Systolic Blood Pressure (mmHg)’. Parameters will be sorted in the order that the 
measurements were collected in on the Vital Signs eCRF page within the tables and listings. 
Vital signs measurements will present summary statistics for the results at the baseline and each 
scheduled post-baseline visit for each of the parameters in Supine and Standing position. In addition, 
summaries will be presented for the change from baseline values at each scheduled post-baseline visit in 
Supine and Standing position (continuous descriptive analysis). The average of triplicate vital signs in 
Supine and Standing position will be used as baseline for HR and BP. 
In addition, vital signs and postural changes, the individual subject level at each time point between the 
two positions in which readings are taken (Supine vs Standing) will be reported. At each timepoint 
standard descriptive stats for HR, sBP and dBP postural data will be reported. 
Further, a categorical tabulation for number (percentage) of subjects per time point (and overall 
categories for any post-exposure timepoint for each parameter separately and for the 2 BP measures 
together) for the following clinically changes will be created: 
• 
Drop in dBP of ≥10mmHg when moving from supine to standing 
• 
Drop in sBP of ≥20mmHg when moving from supine to standing 
• 
Increase in HR of ≥30bpm when moving from supine to standing 
The decimal precision to which the summaries for each parameter will presented will be based on the 
maximum number of decimals to which the results were reported on the eCRF. 
 
11.4 
12-Lead Electrocardiogram (ECG) 
The following ECG measurements will be taken at the time points specified in the Schedule of Events 
(refer to the Protocol): 
• 
Heart Rate (bpm) 
• 
QT interval (msec) 
• 
PR interval (msec) 
• 
QRS interval (msec) 
• 
RR Interval (msec) 
• 
QTcF (msec) 
• 
QTcB (msec) 
• 
ECG clinical interpretation 
All ECG data collected at scheduled and unscheduled visits will be included in the listings, but only 
results collected as scheduled visits will be included in the summary tables. 
The parameter names that will be used in the outputs will comprise of the test name and the unit of 
measure, for example, ‘Ventricular Rate (beats/min)’. Parameters will be sorted in the order that the 
measurements were collected in on the ECG eCRF page within the tables and listings. 
ECG measurements will present summary statistics for the results at the baseline and each scheduled 
post-baseline visit for each of the parameters. In addition, summaries will be presented for the change 
from baseline values at each scheduled post-baseline visit (continuous descriptive analysis). The average 
of the replicate measurements should be determined after the derivation of the individual parameter at 
each time point. 
If multiple tracings are done as part of one assessment, the mean of the three tracings per parameter and 
the worst clinical interpretation per timepoint will be summarized for each participant. All values will 
be listed including the mean value per parameter and the worst clinical interpretation. Changes from 
baseline will be calculated based on the mean values of the triplicates where appropriate. The summary 
of overall interpretation findings table will present counts and percentages for the reported results at 
baseline and each post-baseline visit/time point. Result categories will be ordered as ‘Normal’, 
‘Abnormal Not Clinically Significant (NCS)’ and ‘Abnormal Clinically Significant (CS)’ (categorical 
descriptive analysis). 


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The decimal precision for each parameter will be based on the maximum number of decimals to which 
the results were reported on the eCRF. 
 
11.5 
CV Telemetry 
By-participant data listings will be created for CV Telemetry at all time points collected in CRF. 
 
11.6 
Neurological Exam 
By-participant data listings will be created for all Neurological examination parameters at all time 
points collected in CRF. 
 
11.7 
Physical Examinations 
By-participant data listings will be created for all physical examination parameters at all time points 
collected in CRF 
 
12. 
CHANGES TO THE PLANNED ANALYSIS 
Changes to planned analysis include: 
 
• 
The following endpoint has been added in relation to PK analysis: To potentially identify 
significative difference between gender of PK parameters in plasma. 
 
• 
Standard descriptive stats for HR, sBP and dBP postural data will be reported using a categorical 
tabulation for number (percentage) of subjects per time point in relation to: 
 
o Drop in dBP of ≥10mmHg when moving from supine to standing 
o Drop in sBP of ≥20mmHg when moving from supine to standing 
o Increase in HR of ≥30bpm when moving from supine to standing 
 
• 
For triplicate vital sign at Day -1/ baseline average value will be used. 
 
• 
Pharmacodynamic Exploratory Endpoints will not be included in the SAP. 
 
• 
To date, RNA/DNA Analysis has not been conducted, and no data is available for the SAP. 
 
• 
No suicidal assessments were conducted as part of this study; therefore, this will not be included 
in data listings. 
 
• 
It was decided that screen failure data will not be entered in the EDC, as it is the site/CRO 
practice for phase 1 studies because there are hundreds of SFs, and this data is not imperative 
for any analysis. 


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• 
INTERIM AND FINAL ANALYSIS 
 
12.1 
Final Analysis (End of Study) 
No interim analysis is planned. 
The final analysis will be conducted after all participants have completed the study, the clinical database 
has been locked, the analysis populations have been approved and the study has been unblinded. 
The final analysis will be based on the final version of the SAP. Any deviations from the planned analysis 
will be documented in the CSR. 


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13. 
SOFTWARE 
• 
SAS® Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA). 
• 
Phoenix WinNonlin® Version 8.3 or higher (Certara, USA). 


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14. 
TABLES 
 
Table Number 
Table Title 
Population 
14.1 
Demographics and Other Baseline Characteristics 
 
14.1.1.1 
Summary of Participant Enrolment and Disposition SAD 
Safety 
14.1.1.2 
Summary of Participant Enrolment and Disposition MAD 
Safety 
14.1.2.1 
Analysis Set SAD 
Safety 
14.1.2.2 
Analysis Set MAD 
Safety 
14.1.3.1 
Summary of Demographics and Baseline Characteristics SAD 
Safety 
14.1.3.2 
Summary of Demographics and Baseline Characteristics MAD 
Safety 
14.1.4.1 
Summary of Medical History SAD 
Safety 
14.1.4.2 
Summary of Medical History MAD 
Safety 
14.2 
PK 
 
14.2.1.1 
Summary of Plasma Concentrations (ng/mL) of CVN766 SAD 
PK 
14.2.1.2 
Summary of Plasma Concentrations (ng/mL) of CVN766 MAD 
PK 
14.2.2.1 
Summary of CSF Concentration (ng/mL) SAD 
PK 
14.2.2.2 
Summary of CSF Concentration (ng/mL) MAD 
PK 
14.2.3.1 
Summary of Urine Concentrations (ng/mL) of CVN766 MAD 
PK 
14.2.4.1 
Summary of Plasma Pharmacokinetic Parameters of CVN766 SAD 
PK 
14.2.4.2 
Summary of Plasma Pharmacokinetic Parameters of CVN766 MAD 
PK 
14.2.5.1 
Summary of Urine Pharmacokinetic Parameters of CVN766 MAD 
PK 
14.2.6.1 
Statistical Analysis of Dose Proportionality for CVN766 SAD 
PK 
14.2.6.2 
Statistical Analysis of Dose Proportionality for CVN766 MAD 
PK 
14.2.7.1 
Food Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters SAD 
PK 
14.2.8.1 
Gender Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters SAD 
PK 
14.2.8.2 
Gender Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters MAD 
PK 
14.3 
Safety 
 
14.3.1.1 
Summary of Concomitant Medication SAD 
Safety 
14.3.1.2 
Summary of Concomitant Medication MAD 
Safety 
14.3.3 
Adverse Events 
 
14.3.3.1.1 
Summary of Overall Treatment Emergent Adverse Events SAD 
Safety 
14.3.3.1.2 
Summary of Overall Treatment Emergent Adverse Events MAD 
Safety 
14.3.3.2.1 
Summary of Treatment Emergent Adverse Events by SOC and PT SAD 
Safety 
14.3.3.2.2 
Summary of Treatment Emergent Adverse Events by SOC and PT MAD 
Safety 
14.3.3.3.1 
Summary of Serious Treatment Emergent Adverse Events by SOC and PT SAD 
Safety 


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Table Number 
Table Title 
Population 
14.3.3.3.2 
Summary of Serious Treatment Emergent Adverse Events by SOC and PT MAD 
Safety 
14.3.3.4.1 
Summary of Treatment Emergent Adverse Events by SOC, PT and Severity SAD 
Safety 
14.3.3.4.2 
Summary of Treatment Emergent Adverse Events by SOC, PT and Severity MAD 
Safety 
14.3.3.5.1 
Summary of Treatment Emergent Adverse Events by SOC, PT and Relationship SAD 
Safety 
14.3.3.5.2 
Summary of Treatment Emergent Adverse Events by SOC, PT and Relationship MAD 
Safety 
14.3.3.6.1 
Summary of TEAE leading to the study discontinuation by SOC and PT SAD 
Safety 
14.3.3.6.2 
Summary of TEAE leading to the study discontinuation by SOC and PT MAD 
Safety 
14.3.3.7.1 
Summary of Overall Frequency of TEAE by PT SAD 
Safety 
14.3.3.7.2 
Summary of Overall Frequency of TEAE by PT MAD 
Safety 
14.3.3.8.1 
Summary of Overall Frequency of Related TEAE by PT SAD 
Safety 
14.3.3.8.2 
Summary of Overall Frequency of Related TEAE by PT MAD 
Safety 
14.3.4 
Laboratory Parameters 
 
14.3.4.1.1.1 
Summary of Hematology & Coagulation SAD 
Safety 
14.3.4.1.1.2 
Summary of Hematology & Coagulation MAD 
Safety 
14.3.4.1.2.1 
Summary of Hematology & Coagulation Shifts from Baseline SAD 
Safety 
14.3.4.1.2.2 
Summary of Hematology & Coagulation Shifts from Baseline MAD 
Safety 
14.3.4.2.1.1 
Summary of Serum Chemistry SAD 
Safety 
14.3.4.2.1.2 
Summary of Serum Chemistry MAD 
Safety 
14.3.4.2.2.1 
Summary of Serum Chemistry Shifts from Baseline SAD 
Safety 
14.3.4.2.2.2 
Summary of Serum Chemistry Shifts from Baseline MAD 
Safety 
14.3.4.3.1 
Summary of Urinalysis SAD 
Safety 
14.3.4.3.2 
Summary of Urinalysis MAD 
Safety 
14.3.5 
Other Safety 
 
14.3.5.1.1 
Summary of Vital Signs SAD 
Safety 
14.3.5.1.2 
Summary of Vital Signs MAD 
Safety 
14.3.5.2.1 
Summary of Orthostatic Vital Signs SAD 
Safety 
14.3.5.2.2 
Summary of Orthostatic Vital Signs MAD 
Safety 
14.3.5.3.1 
Categorical Tabulation of Orthostatic Vital Signs SAD 
Safety 
14.3.5.3.2 
Categorical Tabulation of Orthostatic Vital Signs MAD 
Safety 
14.3.5.4.1.1 
Summary of 12-Lead ECG SAD 
Safety 
14.3.5.4.1.2 
Summary of 12-Lead ECG MAD 
Safety 
14.3.5.4.2.1 
Summary of 12-Lead ECG Interpretation SAD 
Safety 
14.3.5.4.2.2 
Summary of 12-Lead ECG Interpretation MAD 
Safety 


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15. 
LISTINGS 
 
Listing Number 
Listing Title 
Population 
16.2.1 
Subject Disposition 
 
16.2.1.1.1 
Analysis Populations SAD 
Safety 
16.2.1.1.2 
Analysis Populations MAD 
Safety 
16.2.1.2.1 
Participant Disposition SAD 
Safety 
16.2.1.2.2 
Participant Disposition MAD 
Safety 
16.2.2 
Protocol Deviations 
 
16.2.2.1 
Protocol Deviations SAD 
Safety 
16.2.2.2 
Protocol Deviations MAD 
Safety 
16.2.4 
Demographic and Other Baseline Data 
 
16.2.4.1.1 
Demographics and Baseline Characteristics SAD 
Safety 
16.2.4.1.2 
Demographics and Baseline Characteristics MAD 
Safety 
16.2.4.2.1 
Medical/Surgical History SAD 
Safety 
16.2.4.2.2 
Medical/Surgical History MAD 
Safety 
16.2.4.3.1 
Hepatitis Panel SAD 
Safety 
16.2.4.3.2 
Hepatitis Panel MAD 
Safety 
16.2.4.4.1 
Alcohol Breath Test SAD 
Safety 
16.2.4.4.2 
Alcohol Breath Test SAD 
Safety 
16.2.4.5.1 
Urine Drug Screen SAD 
Safety 
16.2.4.5.2 
Urine Drug Screen MAD 
Safety 
16.2.4.6.1 
Follicle-Stimulating Hormone Test SAD 
Safety 
16.2.4.6.2 
Follicle-Stimulating Hormone Test MAD 
Safety 
16.2.4.7.1 
Pregnancy Test SAD 
Safety 
16.2.4.7.2 
Pregnancy Test MAD 
Safety 
16.2.4.8.1 
Eligibility Criteria SAD 
Safety 
16.2.4.8.2 
Eligibility Criteria MAD 
Safety 
16.2.5 
Treatment Administration 
 


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Listing Number 
Listing Title 
Population 
16.2.5.1.1 
Participant Randomization SAD 
Safety 
16.2.5.1.2 
Participant Randomization MAD 
Safety 
16.2.5.2.1 
Study Drug Administration SAD 
Safety 
16.2.5.2.2 
Study Drug Administration MAD 
Safety 
16.2.5.3.1 
Meal Records SAD 
Safety 
16.2.6 
PK/PD 
 
16.2.6.1.1 
Plasma Concentration for CVN766 SAD 
PK 
16.2.6.1.2 
Plasma Concentration for CVN766 MAD 
PK 
16.2.6.2.1 
Urine Concentration of CVN766 MAD 
PK 
16.2.6.3.1 
PK Plasma Parameter for CVN766 SAD 
PK 
16.2.6.3.2 
PK Plasma Parameter for CVN766 MAD 
PK 
16.2.6.4.1 
PK Urine Parameter for CVN766 MAD 
PK 
16.2.6.5.1 
CSF Collection Concentration SAD 
PK 
16.2.6.5.2 
CSF Collection Concentration MAD 
PK 
16.2.6.6.1 
CV Telemetry SAD 
PK 
16.2.7 
Adverse Events 
 
16.2.7.1.1 
Adverse Events SAD 
Safety 
16.2.7.1.2 
Adverse Events MAD 
Safety 
16.2.7.2.1 
Serious Adverse Events SAD 
Safety 
16.2.7.2.2 
Serious Adverse Events MAD 
Safety 
16.2.8 
Laboratory Parameters 
 
16.2.8.1.1 
Hematology & Coagulation 
Safety 
16.2.8.1.2 
Hematology & Coagulation MAD 
Safety 
16.2.8.2.1 
Serum Chemistry SAD 
Safety 
16.2.8.2.2 
Serum Chemistry MAD 
Safety 
16.2.8.3.1 
Urinalysis SAD 
Safety 
16.2.8.3.2 
Urinalysis SAD 
Safety 
16.2.9 
Other Safety 
 
16.2.9.1.1 
Vital Signs SAD 
Safety 


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Listing Number 
Listing Title 
Population 
16.2.9.1.2 
Vital Signs MAD 
Safety 
16.2.9.2.1 
12-Lead ECG SAD 
Safety 
16.2.9.2.2 
12-Lead ECG MAD 
Safety 
16.2.9.3.1 
Neurological Exam SAD 
Safety 
16.2.9.3.2 
Neurological Exam MAD 
Safety 
16.2.9.4.1 
Physical Examination SAD 
Safety 
16.2.9.4.2 
Physical Examination MAD 
Safety 
16.2.10 
Prior & Concomitant Medication 
 
16.2.10.1.1 
Prior Medication SAD 
Safety 
16.2.10.1.2 
Prior Medication MAD 
Safety 
16.2.10.2.1 
Concomitant Medication SAD 
Safety 
16.2.10.2.2 
Concomitant Medication MAD 
Safety 
16.2.11 
Comments 
 
16.2.11.1 
Comments 
Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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16. 
FIGURES 
 
 
Figure Number 
Figure Title 
Population 
14.2 
PK 
 
14.2.1.1.1 
Individual Plasma Concentrations of CVN766 vs Time Post-Dose (Linear) SAD 
PK 
14.2.1.1.2 
Individual Plasma Concentrations of CVN766 vs Time Post-Dose (Linear) MAD 
PK 
14.2.1.1.3 
Individual Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Linear) MAD 
PK 
14.2.1.2.1 
Individual Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) SAD 
PK 
14.2.1.2.2 
Individual Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD 
PK 
14.2.1.2.3 
Individual Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD 
PK 
14.2.2.1.1 
Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Linear) SAD 
PK 
14.2.2.1.2 
Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Linear) MAD 
PK 
14.2.2.1.3 
Mean (+/- SD) Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Linear) MAD 
PK 
14.2.2.2.1 
Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) SAD 
PK 
14.2.2.2.2 
Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD 
PK 
14.2.2.2.3 
Mean (+/- SD) Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD 
PK 
14.2.3.1.1 
Plasma Cmax versus dose for CVN766 SAD (Log Scale) 
PK 
14.2.3.1.2 
Plasma Cmax,ss versus dose for CVN766 MAD (Log Scale) 
PK 
14.2.3.2.1 
Plasma AUCinf versus dose for CVN766 SAD (Log Scale) 
PK 
14.2.3.3.1 
Plasma AUC24 versus dose for CVN766 SAD (Log Scale) 
PK 
14.2.3.3.2 
Plasma AUC24 versus dose for CVN766 MAD (Log Scale) 
PK 
14.2.3.4.1 
Plasma AUCt versus dose for CVN766 SAD (Log Scale) 
PK 
14.2.3.5.2 
Plasma AUCt versus dose for CVN766 MAD (Log Scale) 
PK 
14.2.3.5.1 
Plasma AUCtau versus dose for CVN766 MAD (Log Scale) 
PK 
14.2.3.6.1 
Plasma t1/2z versus dose for CVN766 SAD (Log Scale) 
PK 
14.2.3.6.2 
Plasma t1/2z versus dose for CVN766 MAD (Log Scale) 
PK 
14.2.4.1.1 
Dose-normalized Cmax versus dose for CVN766 SAD 
PK 
14.2.4.1.2 
Dose-normalized Cmax,ss versus dose for CVN766 MAD 
PK 
14.2.4.2.1 
Dose-normalized AUCinf versus dose for CVN766 SAD 
PK 
14.2.4.3.1 
Dose-normalized AUC24 versus dose for CVN766 SAD 
PK 
14.2.4.3.2 
Dose-normalized AUC24 versus dose for CVN766 MAD 
PK 
14.2.4.4.1 
Dose-normalized AUCt versus dose for CVN766 SAD 
PK 
14.2.4.4.2 
Dose-normalized AUCt versus dose for CVN766 MAD 
PK 
14.2.4.5.1 
Dose-normalized AUCtau versus dose for CVN766 MAD 
PK 


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Figure Number 
Figure Title 
Population 
14.2.4.6.1 
Dose-normalized t1/2z versus dose for CVN766 SAD 
PK 
14.2.4.6.2 
Dose-normalized t1/2z versus dose for CVN766 MAD 
PK 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol Number: CVN766-101 
2022-10-20 
Document status: Version 1.0 
 
17. 
REFERENCES 
1) 
Clinical Study protocol version 4.0 amendment 3 dated 19 May 2022. 
2) 
Note of Amendment dated 26 September 2022. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Mock Tables 
Table of Contents 
Table 14.1.1.1 Summary of Participant Enrolment and Disposition SAD (Safety Population) ......................................................... 8 
Table 14.1.1.2 Summary of Participant Enrolment and Disposition MAD (Safety Population) ......................................................... 9 
Table 14.1.2.1 Analysis Set SAD (Safety Population) ............................................................................................ 10 
Table 14.1.2.2 Analysis Set MAD (Safety Population) ............................................................................................ 10 
Table 14.1.3.1 Summary of Demographics and Baseline Characteristics SAD (Safety Population) .................................................... 11 
Table 14.1.3.1 Summary of Demographics and Baseline Characteristics SAD (Safety Population) .................................................... 13 
Table 14.1.3.2 Summary of Demographics and Baseline Characteristics MAD(Safety Population) ..................................................... 14 
Table 14.1.4.1 Summary of Medical History SAD (Safety Population) .............................................................................. 15 
Table 14.1.4.1 Summary of Medical History MAD(Safety Population) ............................................................................... 16 
Table 14.2.1.1 Summary of Plasma Concentrations (ng/mL) of CVN766 SAD (PK Population) .......................................................... 17 
Table 14.2.1.2 Summary of Plasma Concentrations (ng/mL) of CVN766 MAD (PK Population) ........................................................... 18 
Table 14.2.2.1 Summary of CSF Concentration (ng/mL) SAD (Pharmacokinetic Population) ........................................................... 19 
Table 14.2.2.2 Summary of CSF Concentration (ng/mL) MAD (Pharmacokinetic Population) ........................................................... 19 
Table 14.2.3.1 Summary of Urine Concentrations (ng/mL) of CVN766 MAD (Pharmacokinetic Population) ............................................... 20 
Table 14.2.4.1 Summary of Plasma Pharmacokinetic Parameters of CVN766 SAD (Pharmacokinetic Population) .......................................... 21 
Table 14.2.4.2 Summary of Plasma Pharmacokinetic Parameters of CVN766 MAD (Pharmacokinetic Population) .......................................... 22 
Table 14.2.5.1 Summary of Urine Pharmacokinetic Parameters of CVN766 MAD (Pharmacokinetic Population) ........................................... 24 
Table 14.2.6.1 Statistical Analysis of Dose Proportionality for CVN766 SAD (Pharmacokinetic Population) ......................................... 25 
Table 14.2.6.2 Statistical Analysis of Dose Proportionality for CVN766 MAD (Pharmacokinetic Population) ......................................... 26 
Table 14.2.7.1 Food Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters SAD(Pharmacokinetic Population) ............................... 27 
Table 14.2.8.1 Gender Effect Assessment of Plasma CVN766 Dose Normalized Pharmacokinetic Parameters SAD (Pharmacokinetic Population) ............ 29 
Table 14.2.8.2 Gender Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters MAD (Pharmacokinetic Population) ............................ 30 
Table 14.3.1.1 Summary of Concomitant Medications SAD (Safety Population) ...................................................................... 32 
Table 14.3.2.2 Summary of Concomitant Medications MAD (Safety Population) ...................................................................... 33 
Table 14.3.3.1.1 Summary of Overall Treatment Emergent Adverse Events SAD (Safety Population) .................................................. 34 
Table 14.3.3.1.2 Summary of Overall Treatment Emergent Adverse Events MAD (Safety Population) .................................................. 34 
Table 14.3.3.2.1 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term SAD (Safety Population) .................. 35 
Table 14.3.3.2.2 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term MAD (Safety Population) .................. 35 
Table 14.3.3.3.1 Summary of Treatment Emergent Serious Adverse Events by System Organ Class and Preferred Term SAD (Safety Population) .......... 36 
Table 14.3.3.3.2 Summary of Treatment Emergent Serious Adverse Events by System Organ Class and Preferred Term MAD (Safety Population) .......... 37 
Table 14.3.3.4.1 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Severity - SAD (Safety Population) ...... 38 
Table 14.3.3.4.2 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Severity MAD (Safety Population) ........ 39 
Table 14.3.3.5.1 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Relationship SAD (Safety Population) .... 40 
Table 14.3.3.5.2 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Relationship MAD (Safety Population) .... 41 
Table 14.3.3.6.1 Summary of TEAE leading to the study discontinuation by SOC and PT SAD (Safety Population) ..................................... 42 
Table 14.3.3.6.2 Summary of TEAE leading to the study discontinuation by SOC and PT MAD (Safety Population) ..................................... 43 
Table 14.3.3.7.1 Summary of Overall Frequency of TEAE by PT SAD (Safety Population) ............................................................ 44 
Table 14.3.3.7.2 Summary of Overall Frequency of TEAE by PT MAD (Safety Population) ............................................................ 45 
Table 14.3.3.8.1 Summary of Overall Frequency of Related TEAE by PT SAD (Safety Population) .................................................... 46 
Table 14.3.3.8.2 Summary of Overall Frequency of Related TEAE by PT MAD (Safety Population) .................................................... 47 
Table 14.3.4.1.1.1 Summary of Hematology and Coagulation SAD (Safety Population) ............................................................... 48 
Table 14.3.4.1.1.2 Summary of Hematology and Coagulation MAD (Safety Population) ............................................................... 49 
Table 14.3.4.1.2.1 Summary of Hematology and Coagulation Shifts from Baseline SAD (Safety Population) ........................................... 50 
Table 14.3.4.1.2.2 Summary of Hematology and Coagulation Shifts from Baseline MAD (Safety Population) ........................................... 51 
Table 14.3.4.2.1.1 Summary of Summary of Chemistry SAD (Safety Population) ..................................................................... 52 
Table 14.3.4.2.1.2 Summary of Summary of Chemistry MAD (Safety Population) ..................................................................... 53 
Table 14.3.4.2.2.1 Summary of Chemistry Shifts from Baseline SAD (Safety Population) ........................................................... 54 
Table 14.3.4.2.2.2 Summary of Chemistry Shifts from Baseline MAD (Safety Population) ........................................................... 55 


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Table 14.3.4.3.1 Summary of Urinalysis SAD (Safety Population) ................................................................................. 56 
Table 14.3.4.3.2 Summary of Urinalysis MAD (Safety Population) ................................................................................. 57 
Table 14.3.5.1.1 Summary of Vital Signs SAD (Safety Population) ................................................................................ 58 
Table 14.3.5.1.2 Summary of Vital Signs MAD (Safety Population) ................................................................................ 59 
Table 14.3.5.2.1 Summary of Orthostatic Vital Signs SAD (Safety Population) .................................................................... 60 
Table 14.3.5.2.2 Summary of Orthostatic Vital Signs MAD (Safety Population) .................................................................... 61 
Table 14.3.5.4.1.2 Summary of 12-Lead ECG MAD (Safety Population) .............................................................................. 65 
Table 14.3.5.4.2.1 Summary of 12-Lead ECG Interpretation SAD (Safety Population) ............................................................... 66 
Table 14.3.5.4.2.2 Summary of 12-Lead ECG Interpretation MAD (Safety Population) ............................................................... 67 
Listing 16.2.1.1.1 Analysis Populations SAD (Safety Population) ................................................................................ 68 
Listing 16.2.1.1.2 Analysis Populations MAD (Safety Population) ................................................................................ 68 
Listing 16.2.1.2.1 Participant Disposition SAD (Safety Population) ............................................................................. 69 
Listing 16.2.1.2.2 Participant Disposition MAD (Safety Population) ............................................................................. 69 
Listing 16.2.2.1 Protocol Deviation SAD (Safety Population) .................................................................................... 70 
Listing 16.2.2.2 Protocol Deviation MAD (Safety Population) .................................................................................... 70 
Listing 16.2.4.1.1 Demographics and Baseline Characteristics SAD (Safety Population) ........................................................... 71 
Listing 16.2.4.1.2 Demographics and Baseline Characteristics MAD (Safety Population) ........................................................... 71 
Listing 16.2.4.2.1 Medical/Surgical History SAD (Safety Population) ............................................................................ 72 
Listing 16.2.4.2.2 Medical/Surgical History MAD (Safety Population) ............................................................................ 72 
Listing 16.2.4.3.1 Hepatitis Panel SAD (Safety Population) ..................................................................................... 73 
Listing 16.2.4.3.2 Hepatitis Panel MAD (Safety Population) ..................................................................................... 73 
Listing 16.2.4.4.1 Alcohol Breath Test SAD (Safety Population) ................................................................................. 74 
Listing 16.2.4.4.2 Alcohol Breath Test SAD MAD (Safety Population) ............................................................................. 74 
Listing 16.2.4.5.1 Urine Drug Screen SAD (Safety Population) ................................................................................... 75 
Listing 16.2.4.5.2 Urine Drug Screen MAD (Safety Population) ................................................................................... 75 
Listing 16.2.4.6.1 Follicle-Stimulating Hormone Test SAD (Safety Population) ................................................................... 76 
Listing 16.2.4.6.2 Follicle-Stimulating Hormone Test MAD (Safety Population) ................................................................... 76 
Listing 16.2.4.7.1 Pregnancy Test SAD (Safety Population) ...................................................................................... 77 
Listing 16.2.4.7.2 Pregnancy Test MAD (Safety Population) ...................................................................................... 77 
Listing 16.2.4.8.1 Eligibility Criteria SAD (Safety Population) ................................................................................ 78 
Listing 16.2.4.8.2 Eligibility Criteria MAD (Safety Population) ................................................................................ 78 
Listing 16.2.5.1.1 Participant Randomization SAD (Safety Population) ........................................................................... 79 
Listing 16.2.5.1.2 Participant Randomization MAD (Safety Population) ........................................................................... 79 
Listing 16.2.5.2.1 Study Drug Administration SAD (Safety Population) ........................................................................... 80 
Listing 16.2.5.2.2 Study Drug Administration MAD (Safety Population) ........................................................................... 80 
Listing 16.2.5.3.1 Meal Records SAD (Safety Population) ........................................................................................ 81 
Listing 16.2.6.1.1 Plasma Concentrations for CVN766 SAD (PK Population) ........................................................................ 82 
Listing 16.2.6.1.2 Plasma Concentrations for CVN766 MAD (PK Population) ........................................................................ 83 
Listing 16.2.6.2.1 Urine Concentration of CVN766 MAD (PK Population) ........................................................................... 85 
Listing 16.2.6.3.1 PK Plasma Parameters for CVN766 SAD (Pharmacokinetic Population) ............................................................ 86 
Listing 16.2.6.3.2 PK Plasma Parameters for CVN766 MAD (Pharmacokinetic Population) ............................................................ 86 
Listing 16.2.6.4.1 PK Urine Parameters for CVN766 MAD (Pharmacokinetic Population) ............................................................. 88 
Listing 16.2.6.5.1 CSF Concentration SAD (Pharmacokinetic Population) .......................................................................... 89 
Listing 16.2.6.5.2 CSF Collection MAD (Pharmacokinetic Population) ............................................................................. 90 
Listing 16.2.6.6.1 CV Telemetry SAD (Pharmacokinetic Population) ............................................................................... 91 
Listing 16.2.7.1.1 Adverse Events SAD (Safety Population) ...................................................................................... 92 
Listing 16.2.7.1.2 Adverse Events MAD (Safety Population) ...................................................................................... 92 
Listing 16.2.7.2.1 Serious Adverse Events SAD (Safety Population) .............................................................................. 93 
Listing 16.2.7.2.2 Serious Adverse Events MAD (Safety Population) .............................................................................. 93 
Listing 16.2.8.1.1 Hematology and Coagulation SAD (Safety Population) .......................................................................... 94 
Listing 16.2.8.1.2 Hematology and Coagulation MAD (Safety Population) .......................................................................... 94 
Listing 16.2.8.2.1 Serum Chemistry SAD (Safety Population) ..................................................................................... 95 
Listing 16.2.8.2.2 Serum Chemistry MAD (Safety Population) ..................................................................................... 95 


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Listing 16.2.8.3.1 Urinalysis SAD (Safety Population) .......................................................................................... 96 
Listing 16.2.8.3.2 Urinalysis MAD (Safety Population) .......................................................................................... 97 
Listing 16.2.9.1.1 Vital Signs SAD (Safety Population) ......................................................................................... 98 
Listing 16.2.9.1.2 Vital Signs - MAD (Safety Population) ....................................................................................... 99 
Listing 16.2.9.2.1 12-Lead ECG SAD (Safety Population) ........................................................................................ 100 
Listing 16.2.9.2.2 12-Lead ECG MAD (Safety Population) ........................................................................................ 101 
Listing 16.2.9.3.1 Neurological Exam SAD (Safety Population) .................................................................................. 102 
Listing 16.2.9.3.2 Neurological Exam MAD (Safety Population) .................................................................................. 103 
Listing 16.2.9.4.1 Physical Examination SAD (Safety Population) ............................................................................... 104 
Listing 16.2.9.4.2 Physical Examination MAD (Safety Population) ............................................................................... 105 
Listing 16.2.10.1.1 Prior Medication SAD (Safety Population) .................................................................................. 106 
Listing 16.2.10.1.2 Prior Medication MAD (Safety Population) .................................................................................. 106 
Listing 16.2.10.2.1 Concomitant Medication SAD (Safety Population) ............................................................................ 107 
Listing 16.2.10.2.2 Concomitant Medication MAD (Safety Population) ............................................................................ 108 
Figure 14.2.1.1.1 Individual Plasma Concentrations of CVN766 vs Time (Linear) SAD (Pharmacokinetic Population) ................................. 109 
Figure 14.2.1.1.2 Individual Plasma Concentrations of CVN766 vs Time (Linear) MAD (Pharmacokinetic Population) ................................. 109 
Figure 14.2.1.1.3 Individual Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Linear) MAD (Pharmacokinetic Population) ............... 110 
Figure 14.2.1.2.1 Individual Plasma Concentrations of CVN766 vs Time (Semi-Log) SAD (Pharmacokinetic Population) ............................... 111 
Figure 14.2.1.2.2 Individual Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) ..................... 112 
Figure 14.2.1.2.3 Individual Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) ............. 113 
Figure 14.2.2.1.1 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Linear) SAD (Pharmacokinetic Population) .................... 114 
Figure 14.2.2.1.2 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time (Linear) MAD (Pharmacokinetic Population) .............................. 115 
Figure 14.2.2.1.3 Mean (+/- SD) Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Linear) MAD (Pharmacokinetic Population) ........... 116 
Figure 14.2.2.2.1 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time (Semi-Log) SAD (Pharmacokinetic Population) ............................ 117 
Figure 14.2.2.2.2 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) .................. 117 
Figure 14.2.2.2.3 Mean (+/- SD) Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) ......... 119 
Figure 14.2.3.1.1 Plasma Cmax versus dose for CVN766 SAD (Log Scale)(Pharmacokinetic Population) ............................................... 120 
Figure 14.2.3.1.2 Plasma Cmax,ss versus dose for CVN766 MAD (Pharmacokinetic Population) ...................................................... 121 
Figure 14.2.3.2.1 Plasma AUCinf versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) ............................................ 122 
Figure 14.2.3.3.1 Plasma AUC24 versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) ............................................. 122 
Figure 14.2.3.3.2 Plasma AUC24 versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) ............................................. 122 
Figure 14.2.3.4.1 Plasma AUCt versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) .............................................. 122 
Figure 14.2.3.4.2 Plasma AUCt versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) .............................................. 122 
Figure 14.2.3.5.1 Plasma AUCtau versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) ............................................ 123 
Figure 14.2.3.6.1 Plasma t1/2z versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) ............................................. 123 
Figure 14.2.3.6.2 Plasma t1/2z versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) ............................................. 123 
Figure 14.2.4.1.1 Dose-normalized Cmax versus dose for CVN766 SAD (Pharmacokinetic Population)................................................. 124 
Figure 14.2.4.1.2 Dose-normalized Cmax,ss versus dose for CVN766 MAD (Pharmacokinetic Population) .............................................. 125 
Figure 14.2.4.2.1 Dose-normalized AUCinf versus dose for CVN766 SAD (Pharmacokinetic Population) ............................................... 125 
Figure 14.2.4.3.1 Dose-normalized AUC24 versus dose for CVN766 SAD (Pharmacokinetic Population) ................................................ 125 
Figure 14.2.4.3.2 Dose-normalized AUC24 versus dose for CVN766 MAD (Pharmacokinetic Population) ................................................ 125 
Figure 14.2.4.4.1 Dose-normalized AUCt versus dose for CVN766 SAD (Pharmacokinetic Population)................................................. 125 
Figure 14.2.4.4.2 Dose-normalized AUCt versus dose for CVN766 MAD (Pharmacokinetic Population)................................................. 126 
Figure 14.2.4.5.1 Dose-normalized AUCtau versus dose for CVN766 MAD (Pharmacokinetic Population) ............................................... 126 
Figure 14.2.4.6.1 Dose-normalized t1/2z versus dose for CVN766 SAD (Pharmacokinetic Population) ................................................ 126 
Figure 14.2.4.6.2 Dose-normalized t1/2z versus dose for CVN766 MAD (Pharmacokinetic Population)................................................ 126 


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GENERAL COMMENTS 
 
• 
Where a count is 0, the percentage will not be shown (e.g. 0(0.0%) will be displayed as 0) 
• 
Unless otherwise states, parameters will be listed in alphabetical order. 
• 
The minimum and maximum values will be presented to the same number of decimal places as recorded in the electronic Case Report Form (eCRF) 
• 
Mean, SD, and Median will be presented to one more decimal place than the raw data 
• 
Percentages will be rounded to one decimal place, with the denominator being the number of subjects in the relevant population with non-missing 
data, unless otherwise specified 
• 
Change from Baseline: 
Change from Baseline will be calculated as: 
Change from Baseline = post baseline value – baseline value 
• 
Percentage change from Baseline 
% Change from Baseline will be calculated as: 
% Change from Baseline = (post baseline value – baseline value)/baseline value x 100 
• 
Unscheduled visits will be excluded from summary tables but included in all by-participant listings. 
• 
Names and order of Treatment Groups for Table Summaries 
o Group 1 = SAD 
o Group 2 = MAD 
 
• 
Names and order of Treatment Groups for Tables/Listings 
• 
SAD: 
o CVN766 5 mg 
o CVN766 15 mg 
o CVN766 45 mg (Fasted) 
o CVN766 45 mg (Fed) 
o CVN766 125 mg 
o CVN766 250 mg 
o Overall CVN766 (Table only) 
o Overall Placebo (Table only) 
o Placebo (Fed; Table only) 
o Overall (Table only) 
o Screening Failures (Listing 16.2.4.7 only) 
Overall CVN766 is the pooled group of all participants with active treatment. The assessments for the participants with active treatments in Cohort S3 
Fed: CVN766 45 mg condition are not counted in ‘Overall CVN766’, and they will be counted under ‘S3 Fed: CVN766 45 mg’. ‘Overall Placebo’ is 
the pooled group of all participants with placebo. The assessments for the participants with placebo in Cohort S3 fed condition are not counted in ‘All 


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Placebo’, and they will be counted under ‘A3/Placebo/Fed’. In demographic and baseline characterises summary tables, Cohort S3 fed condition is not 
needed as appropriate. 
 
• 
MAD: 
o CVN766 45 mg 
o CVN766 125 mg 
o CVN766 250 mg 
o Overall CVN766 
o Overall Placebo 
o Overall 
 
Overall CVN766 is the pooled group of all participants with active treatment. Overall Placebo is the pooled group of all participants with placebo. 
• 
Treatment Display for Summary Tables 
Summary tables will be generally displayed in the following format. If extra dosing group is added due to protocol amendment, the extra dosing group 
will be added in the analysis without further amendment of this template document. 
If limited by the page space, columns have to be displayed in different pages. 
 
Overall is not needed for PK analyses. 
 
SAD 
 
 
CVN766 5 mg 
(N=xx) 
 
CVN766 15 mg 
(N=xx) 
CVN766 45 mg 
(Fasted) 
(N=xx) 
CVN766 45 mg 
(Fed) 
(N=xx) 
 
CVN766 125 
mg (N=xx) 
 
CVN766 250 
mg (N=xx) 
Overall 
CVN766 
(N=xx) 
Overall 
Placebo 
(N=xx) 
 
Placebo 
(Fed) (N=xx) 
 
Overall 
(N=xx) 
 
MAD 
 
 
CVN766 45 mg 
(N=xx) 
 
CVN766 125 mg 
(N=xx) 
 
CVN766 240 mg 
(N=xx) 
 
Overall CVN766 
(N=xx) 
 
Overall Placebo 
(N=xx) 
 
 
Overall (N=xx) 
 
• 
Names and order of Treatment Groups for Listings 
 
SAD 
o Cohort 1/ CVN766 5 mg 
o Cohort 1/ Placebo 


Protocol No: CVN766-101 
Document status: Mock EOS Tables, Listings & Figures, Draft Version 1.0 
2022-10-20 
Novotech – Strictly Confidential 
Page 6 of 126 
 
 
 
o Cohort 2/ CVN766 15 mg 
o Cohort 2/ Placebo 
o Cohort 3 (Fed)/ CVN766 45 mg 
o Cohort 3 (Fed)/ Placebo 
o Cohort 3 (Fasted)/ CVN766 45 mg 
o Cohort 3 (Fasted)/ Placebo 
o Cohort 4/ CVN766 125 mg 
o Cohort 4/ Placebo 
o Cohort 5/ CVN766 250 mg 
o Cohort 5/ Placebo 
o Screening Failures (Listing 16.2.4.7 only) 
 
MAD 
o Cohort 1/ CVN766 45 mg 
o Cohort 1/ Placebo 
o Cohort 2/ CVN766 125 mg 
o Cohort 2/ Placebo 
o Cohort 3/ CVN766 250 mg 
o Cohort 3/ Placebo 
• 
Names of visits 
• 
SAD Cohorts 1, 2, 3a, 4, 5. 
o Visit 1 = Screening 
o Visit 2 = Day -1 
o Visit 3 = Day 1 
o Visit 4 = Day 2 
o Visit 5 = Day 3 
o Visit 6 = Day 4 / Discharge 
o Visit 7 = Day 8 / Outpatient Visit 
o Visit 8 = Day 14 / Follow up / Early Termination 
• 
SAD Cohorts 3 
o Visit 1 = Screening (Listing only) 
o Visit 2 = Day -1 
o Visit 3 = Day 1 
o Visit 4 = Day 2 
o Visit 5 = Day 3 


Protocol No: CVN766-101 
Document status: Mock EOS Tables, Listings & Figures, Draft Version 1.0 
2022-10-20 
Novotech – Strictly Confidential 
Page 7 of 126 
 
 
 
o Visit 6 = Day 4 / Discharge Day 
o Visit 7 = Day 8 
o Visit 8 = Day 21 
o Visit 9 = Day 22 
o Visit 10 = Day 23 
o Visit 11 = Day 24 
o Visit 12 = Day 28 / Discharge 
o Visit 13 = Day 42 / Follow up / Early Termination 
• 
MAD Cohorts 1, 2, 3 
o Visit 1 = Screening (Listing only) 
o Visit 2 = Day -1 
o Visit 3 = Day 1 
o Visit 4 = Day 2 
o Visit 5 = Day 3 
o Visit 6 = Day 4 
o Visit 7 = Day 5 
o Visit 8 = Day 6 
o Visit 9 = Day 7 
o Visit 10 = Day 8 
o Visit 11 = Day 9/ Inpatient discharge 
o Visit 12 = Day 10/ Outpatient visit 
o Visit 13 = Day 14/ Outpatient visit 
o Visit 14 = Day 21/ Follow up/ Early Termination 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 8 of 126 
 
 
Programing Note: 
Source Listing: 16.2.1.2.1 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg (Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo, Placebo 
(Fed) and Overall. 
 
Table 14.1.1.1 Summary of Participant Enrolment and Disposition SAD (Safety Population) 
 
 
 
 
CVN766 5 mg 
(N=xx) 
CVN766 15 mg 
(N=xx) 
 
Etc. 
Overall 
(N=xx) 
 
 
Number of Participants who Completed the Study 
 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
 
 
xx (xx.x%) 
 
Number of Participants who did not Complete the Study 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
Primary Reason for Non-Completion 
 
 
 
 
Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Failure to Meet Randomization Criteria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Lost to Follow Up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Non-compliance with Study Drug 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Physician Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Screen Failure 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Site Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Study Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Technical Problems 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the all randomized population in 
each treatment group (N). 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 9 of 126 
 
 
Programing Note: 
Same as Table 14.1.1.1 
Source Listing: 16.2.1.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.1.1.2 Summary of Participant Enrolment and Disposition MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 10 of 126 
 
 
Programing Note: 
Source Listing: 16.2.1.1.1 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg (Fed) CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo, Placebo 
(Fed) and Overall. 
 
Table 14.1.2.1 Analysis Set SAD (Safety Population) 
 
 
CVN766 5 mg 
(N=xx) 
 
etc. 
Overall 
(N=xx) 
 
All Enrolled 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
Pharmacokinetic Population 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Safety Population 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Table 14.1.2.2 Analysis Set MAD (Safety Population) 
 
Programing Note: 
Same as Table 14.1.2.1 
Source Listing: 16.2.1.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 11 of 126 
 
 
 
Table 14.1.3.1 Summary of Demographics and Baseline Characteristics SAD (Safety Population) 
 
 
Parameter 
 
Statistic 
CVN766 5 mg 
(N=xx) 
 
etc. 
Overall 
(N=xx) 
 
Age (years) at Screening 
 
n 
 
xx 
 
xx 
 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
x.x 
x.x 
x.x 
 
Minimum 
xx 
xx 
xx 
 
Maximum 
xx 
xx 
xx 
 
Sex n(%) 
 
Female 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Unknown 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Undifferentiated 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Childbearing Potential n(%)* 
 
Yes 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Is subject current smoker? 
 
Yes 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Race n (%) 
 
Asian 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Ethnicity n(%) 
 
Hispanic or Latino 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Not Reported 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Unknown 
 
 
 
 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 12 of 126 
 
 
 
 
Parameter 
 
Statistic 
CVN766 5 mg 
(N=xx) 
 
etc. 
Overall 
(N=xx) 
 
Source Listing: 16.2.4.1.1 
 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the all 
randomized population in each treatment group (N). 
*For childbearing potential, percentages are based on the number of female participants. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 13 of 126 
 
 
 
Table 14.1.3.1 Summary of Demographics and Baseline Characteristics SAD (Safety Population) 
 
 
Parameter 
 
Statistic 
CVN766 5 mg 
(N=xx) 
 
etc. 
Overall 
(N=xx) 
 
Weight (kg) at Screening 
 
n 
 
xx 
 
xx 
 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Minimum 
xx 
xx 
xx 
 
Maximum 
xx 
xx 
xx 
 
Height (cm) at Screening 
 
n 
 
xx 
 
xx 
 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Minimum 
xx 
xx 
xx 
 
Maximum 
xx 
xx 
xx 
 
Body Mass Index(kg/m2) at Screening 
 
n 
 
xx 
 
xx 
 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Minimum 
xx 
xx 
xx 
 
Maximum 
xx 
xx 
xx 
Source Listing: 16.2.4.1.1 
 
SD: Standard Deviation. Percentages are calculated (the denominator used for the calculation) based on the number of participants in the all 
randomized population in each treatment group (N). 
*For childbearing potential, percentages are based on the number of female participants. 
 
Programing Note: 
Source Listing: 16.2.4.1.1 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg (Fed) CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo, Placebo(Fed) 
and Overall. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 14 of 126 
 
 
 
Table 14.1.3.2 Summary of Demographics and Baseline Characteristics MAD(Safety Population) 
 
Programing Note: 
Same as Table 14.1.3.1 
Source Listing: 16.2.4.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 15 of 126 
 
 
Programing Note: 
Source Listing: 16.2.4.2.1 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg (Fed) CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo, Placebo(Fed) 
and Overall. 
 
Table 14.1.4.1 Summary of Medical History SAD (Safety Population) 
 
 
Parameter 
CVN766 5 mg 
(N=xx) 
 
etc. 
Overall 
(N=xx) 
 
Subjects with at least one Medical History 
 
xx 
 
xx 
 
xx 
 
xx.x 
xx.x 
xx.x 
Subjects with at least one ongoing Medical History 
xx.x 
xx.x 
xx.x 
 
xx.x 
xx.x 
xx.x 
Ongoing Medical History 
xx 
xx 
xx 
SOC1 
xx 
xx 
xx 
PT1 
 
 
 
 
SOC2 
 
 
 
PT1 
 
 
 
PT2 
 
 
 
Etc… 
 
 
 
 
Past (not ongoing) Medical History 
 
 
 
SOC1 
 
 
 
PT1 
 
 
 
 
SOC2 
 
 
 
PT1 
 
 
 
PT2 
 
 
 
Etc… 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 16 of 126 
 
 
 
Table 14.1.4.1 Summary of Medical History MAD(Safety Population) 
 
Programing Note: 
Same as Table 14.1.4.1 
Source Listing: 16.2.4.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 17 of 126 
 
 
Programing Note: 
 
Add following treatment rows; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg (Fed), CVN766 125 mg, CVN766 250 mg. 
 
 
Table 14.2.1.1 Summary of Plasma Concentrations (ng/mL) of CVN766 SAD (PK Population) 
Analyte:xxx 
 
 
 
Treatment 
 
 
Visit 
 
 
Timepoints 
 
 
n 
 
 
nBLQ 
 
 
Mean 
 
 
SD 
 
 
CV% 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
Geometric 
Mean 
 
Geometric 
CV% 
 
CVN766 5 mg 
(N=xx) 
 
 
Day 1 
 
 
Pre-dose 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
1h 
 
 
 
 
 
 
 
 
 
 
 
 
1.5h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
2h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
3h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
5h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
8h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
12h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
16h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 2 
24h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
36h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 3 
48h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 4 
72h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
CVN766 15 mg 
(N=xx) 
 
Day 1 
 
Pre-dose 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
Source Listing: 16.2.6.1.1 
BLQ = Below Limit of Quantitation; CV% = Coefficient of Variation; SD = Standard Deviation. 
BLQ is set as 0 for standard statistics (such as arithmetic mean),and set as missing for geometric statistics. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 18 of 126 
 
 
Programing Note: 
Source Listing: 16.2.6.1.2; 
Add following treatment rows; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Table 14.2.1.2 Summary of Plasma Concentrations (ng/mL) of CVN766 MAD (PK Population) 
Analyte:xxx 
 
 
 
Treatment 
 
Visit 
 
Timepoint 
 
n 
 
nBLQ 
 
Mean 
 
SD 
 
CV% 
 
Median 
 
Minimum 
 
Maximum 
Geometric 
Mean 
Geometric 
CV% 
 
CVN766 45 mg 
(N=xx) 
 
 
Day 1 
 
 
Pre-dose 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
0.5h 
 
 
 
 
 
 
 
 
 
 
 
 
1h 
 
 
 
 
 
 
 
 
 
 
 
 
1.5h 
 
 
 
 
 
 
 
 
 
 
 
 
….. 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
24h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 3 
Pre-dose 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 4 
Pre-dose 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 5 
Pre-dose 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 6 
Pre-dose 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 7 
Pre-dose 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
0.5h 
 
 
 
 
 
 
 
 
 
 
 
 
1h 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
16h 
 
 
 
 
 
 
 
 
 
 
 
Day 8 
24h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
36h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 9 
48h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Day 10 
72h 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
CVN766 125 mg 
(N=xx) 
 
Day 1 
 
Pre-dose 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
… 
 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
BLQ = Below Limit of Quantitation; CV% = Coefficient of Variation; SD = Standard Deviation. 
BLQ is set as 0 for standard statistics (such as arithmetic mean), and set as missing for geometric statistics. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 19 of 126 
 
 
Programing Note: 
Source Listing: 16.2.6.5.1; 
Add following treatment; 
CVN766 45 mg (Fasted). 
Programing Note: 
Source Listing: 16.2.6.5.2; 
Add following treatment; 
CVN766 45 mg 
 
Table 14.2.2.1 Summary of CSF Concentration (ng/mL) SAD (Pharmacokinetic Population) 
Analyte: xxx 
 
 
 
Treatment 
 
Visit 
 
Timepoint 
 
n 
 
nBLQ 
 
Mean 
 
SD 
 
CV% 
 
Median 
 
Minimum 
 
Maximum 
Geometric 
Mean 
Geometric 
CV% 
 
CVN766 45 mg 
(Fasted) (N=xx) 
 
 
Day 1 
 
3h post- 
dose 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
BLQ = Below Limit of Quantitation; CV% = Coefficient of Variation; SD = Standard Deviation. 
BLQ is set as 0 for standard statistics (such as arithmetic mean), and set as missing for geometric statistics. 
 
 
 
 
 
Table 14.2.2.2 Summary of CSF Concentration (ng/mL) MAD (Pharmacokinetic Population) 
 
 
 
Treatment 
 
Visit 
 
Timepoint 
 
n 
 
nBLQ 
 
Mean 
 
SD 
 
CV% 
 
Median 
 
Minimum 
 
Maximum 
 
Geometric Mean 
Geometric 
CV% 
 
 
CVN766 45 mg (N=xx) 
 
 
Day 7 
 
3h Post- 
dose 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
BLQ = Below Limit of Quantitation; CV% = Coefficient of Variation; SD = Standard Deviation. 
BLQ is set as 0 for standard statistics (such as arithmetic mean), and set as missing for geometric statistics. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 20 of 126 
 
 
Programing Note: 
Source Listing: 16.2.6.2.1; 
Add following treatment rows; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
 
 
Table 14.2.3.1 Summary of Urine Concentrations (ng/mL) of CVN766 MAD (Pharmacokinetic Population) 
 
Analyte: xxx 
 
 
 
Treatment 
 
Visit 
 
Timepoints 
 
n 
 
nBLQ 
 
Mean 
 
SD 
 
CV% 
 
Median 
 
Minimum 
 
Maximum 
Geometric 
Mean 
Geometric 
CV% 
 
CVN766 45 mg 
(N=xx) 
 
 
Day 1 
 
 
Pre-dose 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
0-6 Hours 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
6-12 Hours 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
12-24 Hours 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
Day 7 
 
0-6 Hours 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
……. 
 
 
 
 
 
 
 
 
 
 
BLQ = Below Limit of Quantitation; CV% = Coefficient of Variation; SD = Standard Deviation. 
BLQ is set as 0 for standard statistics (such as arithmetic mean), and set as missing for geometric statistics. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 21 of 126 
 
 
Programing Note: 
 
Add following treatment rows; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
 
 
 
Table 14.2.4.1 Summary of Plasma Pharmacokinetic Parameters of CVN766 SAD (Pharmacokinetic Population) 
Analyte: xxx 
Visit: Day 1 
 
 
 
Treatment 
 
Parameter 
 
n 
 
n NC 
 
Mean 
 
SD 
 
Median 
 
Minimum 
 
Maximum 
Geometric 
Mean 
Geometric 
CV% 
 
CVN766 5 mg (N=xx) 
 
Cmax (unit) 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
Tmax (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Tlast (unit) 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx.x 
 
AUC24 (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
AUCt (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
AUCinf (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
AUC%extrap (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
λz (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
t½ (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
CL/F 
(unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
Vz/F (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
CSF:Plasma (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
DN_Cmax (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
DN_AUC24hr (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
DN_AUCt (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
DN_AUCinf (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
CVN766 15 mg (N=xx) 
 
Cmax(unit) 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
Tmax(unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
… 
… 
 
 
 
 
 
 
 
 
 
Source Listing: 16.2.6.3.1 
N/A: = Not Applicable NC = Not Calculable; SD = Standard Deviation. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 22 of 126 
 
 
 
Table 14.2.4.2 Summary of Plasma Pharmacokinetic Parameters of CVN766 MAD (Pharmacokinetic Population) 
Analyte: xxx 
Day 1 
 
 
Treatment 
 
 
Parameter 
 
 
n 
 
 
n NC 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
Geometric 
Mean 
 
Geometric 
CV% 
 
 
CVN766 45 mg (N=xx) 
 
 
Cmax 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
Cmin, 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
Ctrough DayN 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Tmax 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Tmin 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
AUCt 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
AUC24 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
CSF:Plasma 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
DN_Cmax,ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
DN_AUC24hr 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
DN_AUCt 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
CVN766 125 mg 
(N=xx) 
 
Cmax(unit) 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
Cmin (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
… 
… 
 
 
 
 
 
 
 
 
 
Source Listing: 16.2.6.3.1 
N/A: = Not Applicable NC = Not Calculable; SD = Standard Deviation. 
 
Analyte: xxx 
Day 7 
 
 
Treatment 
 
 
Parameter 
 
 
n 
 
 
n NC 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
Geometric 
Mean 
 
Geometric 
CV% 
 
 
CVN766 45 mg (N=xx) 
 
 
Cmax, ss 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
Cmin,ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
Ctrough DayN 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Cavg,ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Tmax, ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Tmin, ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 23 of 126 
 
 
Programing Note: 
Source Listing: 16.2.6.3.2 
Add following treatment rows; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Repeat: Day 1, Day 7 
 
 
 
Treatment 
 
 
Parameter 
 
 
n 
 
 
n NC 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
Geometric 
Mean 
 
Geometric 
CV% 
 
Tlast, ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
AUCt 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
AUCtau 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
AUCinf 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
λz or Kel 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
t½ 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
CL/Fss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
Vz/Fss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
RACmax 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
RAAUC 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
CSF:Plasma 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
DN_Cmax,ss 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
DN_AUCt 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
DN_AUCtau 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
DN_AUCinf 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
CVN766 125 mg 
(N=xx) 
 
Cmax(unit) 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
xx.x 
 
xx.x 
 
Cmin,ss(unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
… 
… 
 
 
 
 
 
 
 
 
 
Source Listing: 16.2.6.3.1 
N/A: = Not Applicable NC = Not Calculable; SD = Standard Deviation. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 24 of 126 
 
 
Programing Note: 
Source Listing: 16.2.6.4.1 
Add following treatment; 
CVN766 45 mg 
Include Visit = Day 1 and Day 7 
 
Table 14.2.5.1 Summary of Urine Pharmacokinetic Parameters of CVN766 MAD (Pharmacokinetic Population) 
Analyte: xxx 
Visit: Day 1 
 
 
Treatment 
 
 
Parameter 
 
 
n 
 
 
n NC 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
Geometric 
Mean 
 
Geometric 
CV% 
 
 
CVN766 45 mg (N=xx) 
 
 
Aet1-t2 (unit) 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
Fet1-t2 (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
CLr (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 
 
 
Analyte: xxx 
Visit: Day 7 
 
 
Treatment 
 
 
Parameter 
 
 
n 
 
 
n NC 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
Geometric 
Mean 
 
Geometric 
CV% 
 
 
CVN766 45 mg (N=xx) 
 
 
Aet1-t2 (unit) 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
Fet1-t2 (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
xx.x 
 
CLr (unit) 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx.x 
xx.x 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 25 of 126 
 
 
 
Table 14.2.6.1 Statistical Analysis of Dose Proportionality for CVN766 SAD (Pharmacokinetic Population) 
Analyte: xxxx 
 
 
 
Intercept 
Estimate 
Slope 
 
Parameter 
n 
Estimate 
90% CI 
 
AUCinf 
 
xx 
 
x.xx 
 
xxx.xx 
 
(x.xx, x.xx) 
AUCt 
xx 
x.xx 
xxx.xx 
(x.xx, x.xx) 
AUC24 
xx 
x.xx 
xxx.xx 
(x.xx, x.xx) 
Cmax 
xx 
x.xx 
xxx.xx 
(x.xx, x.xx) 
Source Listing: 16.2.6.3.1 
CI = Confidence Interval. 
Power Model: Ln(PK)=intercept + Ln(dose) 
 
Dose proportionality can generally be concluded if the 90% CIs around the slope estimate (i.e., β1) include the value of 1 and is supported by 
the descriptive and graphical interpretation. 
 
Programing Note: 
Include only the following cohorts; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 26 of 126 
 
 
 
 
 
Table 14.2.6.2 Statistical Analysis of Dose Proportionality for CVN766 MAD (Pharmacokinetic Population) 
 
Analyte: xxx 
Day 1 
 
 
Intercept 
Estimate 
Slope 
 
Parameter 
n 
Estimate 
90% CI 
 
AUC24 
 
xx 
 
x.xx 
 
xxx.xx 
 
(x.xx, x.xx) 
Cmax 
xx 
x.xx 
xxx.xx 
(x.xx, x.xx) 
Source Listing: 16.2.6.3.2 
CI = Confidence Interval. 
Power Model: Ln(PK)=intercept + Ln(dose) 
 
 
Analyte: xxx 
Day 7 
 
 
Intercept 
Estimate 
Slope 
 
Parameter 
n 
Estimate 
90% CI 
 
AUCtau 
 
xx 
 
x.xx 
 
xxx.xx 
 
(x.xx, x.xx) 
Cmax,ss 
xx 
x.xx 
xxx.xx 
(x.xx, x.xx) 
Source Listing: 16.2.6.3.2 
CI = Confidence Interval. 
Power Model: Ln(PK)=intercept + Ln(dose) 
 
Dose proportionality can generally be concluded if the 90% CIs around the slope estimate (i.e., β1) include the value of 1 and is supported by 
the descriptive and graphical interpretation. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 27 of 126 
 
 
 
Table 14.2.7.1 Food Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters SAD(Pharmacokinetic Population) 
 
Analyte:xxxx 
 
 
Parameter (Unit)/ 
Statistics 
CVN766 45 mg 
Fasted 
(N=xx) 
CVN766 45 mg 
Fed 
(N=xx) 
 
AUCt(Unit) 
 
 
n 
xx.xx 
xx.xx 
Geometric LS Mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx xx.xx, xx.xx) 
Ratio of Geometric LS Means (Fed/Fasting) 
 
xx.xx 
90% CI for Ratio of Geometric LS Means (Fed/Fasting) 
 
(xx.xx, xx.xx) 
 
AUCinf (Unit) 
 
 
n 
xx.xx 
xx.xx 
Geometric LS Mean 
xx.xx 
xx.xx 
Ratio of Geometric LS Means (Fed/Fasting) 
 
xx.xx 
90% CI for Ratio of Geometric LS Means (Fed/Fasting) 
 
(xx.xx, xx.xx) 
 
AUC24 (Unit) 
 
 
n 
xx.xx 
xx.xx 
LS Mean (SE) 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
Geometric LS Mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx xx.xx, xx.xx) 
Ratio of Geometric LS Means (Fed/Fasting) 
 
xx.xx 
 
Cmax (Unit) 
 
 
n 
xx.xx 
xx.xx 
Geometric LS Mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx xx.xx, xx.xx) 
Ratio of Geometric LS Means (Fed/Fasting) 
 
xx.xx 
90% CI for Ratio of Geometric LS Means (Fed/Fasting) 
 
(xx.xx, xx.xx) 
Source: Listing 16.2.6.3.1 
LS = Least Square, SE = Standard Error, CI = Confidence Interval. 
 
Programming Note: 
• 
ANOVA model will be used 
 
Fixed Effect: food status (fed, fasted) 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 28 of 126 
 
 
 
Random Effect: Subject 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 29 of 126 
 
 
Programing Note: 
Include only the following cohorts; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg 
 
Table 14.2.8.1 Gender Effect Assessment of Plasma CVN766 Dose Normalized Pharmacokinetic Parameters SAD (Pharmacokinetic Population) 
 
Analyte:xxxx 
Visit: Day 1 
Gender 
Treatment 
Parameter 
Statistics 
Male 
Female 
Pooled CVN766 
AUC24/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
Cmax/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
AUCt/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
AUCinf/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
T1/2z 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
Tmax 
n 
xx 
xx 
 
 
Hodges-Lehmann estimate 
(Median) 
xx.xx 
xx.xx 
 
 
Hodges-Lehmann CI 
 
xx.xx (xx.xx, xx.xx) 
 
 
Source: Listing 16.2.6.3.1 
LS = Least Square, SE = Standard Error, CI = Confidence Interval. 
 
Programming Note: 
• 
ANOVA model will be used 
 
Fixed Effect: Gender (Male, Female) 
 
Random Effect: Subject 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 30 of 126 
 
 
 
Table 14.2.8.2 Gender Effect Assessment of Plasma CVN766 Pharmacokinetic Parameters MAD (Pharmacokinetic Population) 
 
Analyte:xxxx 
Day 1 
Gender 
Treatment 
Parameter 
Statistics 
Male 
Female 
Pooled CVN766 
AUC24/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
Cmax/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
AUCt/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
T1/2z 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
Tmax 
n 
xx 
xx 
 
 
Hodges-Lehmann estimate 
(Median) 
xx.xx 
xx.xx 
 
 
Hodges-Lehmann CI 
 
xx.xx (xx.xx, xx.xx) 
 
Analyte:xxxx 
Day 7 
Gender 
Treatment 
Parameter 
Statistics 
Male 
Treatment 
 
Cmax,ss/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
AUCtau/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
AUCt/Dose 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
T1/2z 
n 
xx 
xx 
 
 
Geometric LS mean (90% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
Geometric mean ratio(90% CI) 
(female vs male) 
 
xx.xx (xx.xx, xx.xx) 
 
Tmax 
n 
xx 
xx 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 31 of 126 
 
 
 
Hodges-Lehmann estimate 
(Median) 
xx.xx 
xx.xx 
 
Source: Listing 16.2.6.3.2 
LS = Least Square, SE = Standard Error, CI = Confidence Interval. 
 
Programming Note: 
• 
ANOVA model will be used 
 
Fixed Effect: Gender (Male, Female) 
 
Random Effect: Subject 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 32 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg( Fed) CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo, Placebo (Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg(Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Table 14.3.1.1 Summary of Concomitant Medications SAD (Safety Population) 
 
 
Anatomical Therapeutic Class (ATC) [Level 3] 
Preferred Term (PT) 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
 
etc. 
Overall 
(N=xx) 
n (%) m 
 
 
Subjects with at least one Concomitant Medication 
 
 
xx (xx.x%) x 
 
 
xx (xx.x%) x 
 
 
xx (xx.x%) x 
 
ATC 3 
 
xx (xx.x%) x 
 
xx (xx.x%) x 
 
xx (xx.x%) x 
PT 1 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
PT 2 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
…. 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
 
ATC 3 
 
xx (xx.x%) x 
 
xx (xx.x%) x 
 
xx (xx.x%) x 
PT 1 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
PT 2 
xx (xx.x%) x 
xx (xx.x%) x 
xx (xx.x%) x 
…… 
 
 
 
Source: Listing 16.2.10.2.1 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of 
the study drug. 
ATC class and preferred names within ATC class are presented in alphabetical order. 
If a participant has multiple occurrences of a concomitant medication, the participant is presented only once in the participant count (n) 
column for a given ATC and PT. Occurrences are counted each time in the mentions/occurrence (m) column. 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
World Health Organization-Drug Dictionary (WHO-DD) Version xx, YYYY 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 33 of 126 
 
 
Programing Note: 
Same as Table 14.3.1.1 
Source: Listing 16.2.10.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.2.2 Summary of Concomitant Medications MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 34 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo, 
Placebo(Fed)and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
Programing Note: 
Same as Table 14.3.3.1.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall 
 
Table 14.3.3.1.1 Summary of Overall Treatment Emergent Adverse Events SAD (Safety Population) 
 
 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
etc. 
Overall 
(N=xx) 
n (%) m 
 
Number of Participants Reporting at least one: 
 
 
 
TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Severe TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Treatment Related TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Serious TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
TEAE leading to study drug withdrawal[1] 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
TEAE leading to discontinuation from study 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Life threatening TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
TEAE leading to death 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (m) column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
[1]Action taken = drug withdrawn 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
Table 14.3.3.1.2 Summary of Overall Treatment Emergent Adverse Events MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 35 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg (Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
Programing Note: 
Same as Table 14.3.3.2.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.3.2.1 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term SAD (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
Overall 
(N=xx) 
n (%) m 
 
etc. 
 
Participants with at least one TEAE 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
SOC1 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
SOC2 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
…. 
 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
Table 14.3.3.2.2 Summary of Treatment Emergent Adverse Events by System Organ Class and Preferred Term MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 36 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg(Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 cohort 
 
Table 14.3.3.3.1 Summary of Treatment Emergent Serious Adverse Events by System Organ Class and Preferred Term SAD (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
Overall 
(N=xx) 
n (%) m 
 
etc. 
 
Participants with at least one Serious TEAE 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
SOC1 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
SOC2 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
…. 
 
 
 
Source: Listing 16.2.7.2.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 37 of 126 
 
 
Programing Note: 
Same as Table 14.3.3.3.1 
Source: Listing 16.2.7.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.3.3.2 Summary of Treatment Emergent Serious Adverse Events by System Organ Class and Preferred Term MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 38 of 126 
 
 
 
Table 14.3.3.4.1 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Severity - SAD (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
Severity 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
etc. 
Overall 
(N=xx) 
n (%) m 
 
Participants with at least one TEAE 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
Mild 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Moderate 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Severe 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Life-threatening 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Death 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Mild 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Moderate 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Severe 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Life-threatening 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Death 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Mild 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Moderate 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Severe 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Life-threatening 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Death 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg(Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 cohort 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 39 of 126 
 
 
Programing Note: 
Same as Table 14.3.3.4.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.3.4.2 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Severity MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 40 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg(Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort 
 
Table 14.3.3.5.1 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Relationship SAD (Safety Population) 
 
System Organ Class (SOC) 
Preferred Term (PT) 
Relationship 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
etc. 
Overall 
(N=xx) 
n (%) m 
 
Participants with at least one TEAE 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
Not Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
SOC1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Not Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Not Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 41 of 126 
 
 
Programing Note: 
Same as Table 14.3.3.5.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.3.5.2 Summary of Treatment Emergent Adverse Events by System Organ Class, Preferred Term and Relationship MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 42 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg(Fed) 
Overall Placebo will not contain Placebo (fed) from S3 Cohort 
 
Table 14.3.3.6.1 Summary of TEAE leading to the study discontinuation by SOC and PT SAD (Safety Population) 
 
 
System Organ Class (SOC) 
Preferred Term (PT) 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
Overall 
(N=xx) 
n (%) m 
 
etc. 
 
Participants with at least one TEAE Leading to Study Discontinuation 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
SOC1 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
… 
 
 
 
SOC2 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
…. 
 
 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 43 of 126 
 
 
Programing Note: 
Same as Table 14.3.3.6.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.3.6.2 Summary of TEAE leading to the study discontinuation by SOC and PT MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 44 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Table 14.3.3.7.1 Summary of Overall Frequency of TEAE by PT SAD (Safety Population) 
 
 
 
Preferred Terms (PTs) 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
etc. 
Overall 
(N=xx) 
n (%) m 
 
Participants with at least one TEAE 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
PT1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT4 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
PT5 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
……. 
 
 
 
 
 
 
….. 
 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 45 of 126 
 
 
Programing Note: 
Same as Table 14.3.3.7.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.3.7.2 Summary of Overall Frequency of TEAE by PT MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 46 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg (Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg (Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Table 14.3.3.8.1 Summary of Overall Frequency of Related TEAE by PT SAD (Safety Population) 
 
 
CVN766 5 mg 
(N=xx) 
n (%) m 
 
etc. 
Overall 
(N=xx) 
n (%) m 
 
Participants with at least one TEAE 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
Not Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
PT1 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
 
xx (xx.x%) xx 
Not Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
….. 
 
 
 
PT2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Not Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
Related 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
….. 
 
 
 
 
Source: Listing 16.2.7.1.1 
 
Treatment Emergent Adverse Events (TEAEs) are defined as adverse events that occurred following the first administration of study medication. 
If a participant has multiple occurrences of a TEAE, the participant is presented only once in the Participant count (n) column for a given System 
Organ Class and Preferred Term. Occurrences are counted each time in the mentions/Occurrence (M) column. 
SOC / PTs will be presented in decreasing order of ‘overall’ column. 
 
Percentages are calculated (the denominator used for the calculation) based on the number of participants in the safety population in each 
treatment group (N). 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 47 of 126 
 
 
Programing Note: 
Same as Table 14.3.3.8.1 
Source: Listing 16.2.7.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
 
 
 
Table 14.3.3.8.2 Summary of Overall Frequency of Related TEAE by PT MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 48 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Repeat for Lab Category: Coagulation and its parameters. 
 
Table 14.3.4.1.1.1 Summary of Hematology and Coagulation SAD (Safety Population) 
 
Lab Category: Hematology 
Parameter: Basophils (unit) 
 
 
 
 
Actual Value 
 
 
 
Change from Baseline[1] 
 
Treatment 
Visit 
n 
Mean 
SD 
Median 
Minimum Maximum 
n 
Mean 
SD 
Median 
Minimum Maximum 
 
CVN766 5 mg 
(N=xx) 
 
Baseline[1] 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
N/A 
 
 
 
 
 
 
Day 1 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 14/ ET 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
CVN766 15 mg 
(N=xx) 
Baseline[1] 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
 
 
 
 
 
 
Day 1 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 14/ ET 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing 16.2.8.1.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable, SD = Standard Deviation, ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 49 of 126 
 
 
Programing Note: 
Same as Table 14.3.4.1.1.1 
Source: Listing 16.2.8.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.4.1.1.2 Summary of Hematology and Coagulation MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 50 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
Repeat for Lab Category: Coagulation and its parameters. 
 
Table 14.3.4.1.2.1 Summary of Hematology and Coagulation Shifts from Baseline SAD (Safety Population) 
 
Lab Category: Hematology 
Parameter: Hemoglobin (unit) 
 
 
 
 
 
 
 
 
Post-Baseline 
 
 
Treatment 
 
Visit 
 
Visit(n)[2] 
Result 
Classification 
Baseline[1] 
n(%) 
Low 
n(%) 
Normal 
n(%) 
High 
n(%) 
 
CVN766 5 mg (N=xx) 
 
Day 1 
 
xx 
 
Low 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 2 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 3 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
….. 
 
 
 
 
 
 
 
Day 14/ET 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
… 
… 
 
 
 
 
Source: Listing 16.2.8.1.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
[2] Number of participants with non-missing values at that visit. 
Participant with both baseline and post-baseline values included. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 51 of 126 
 
 
Programing Note: 
Same as Table 14.3.4.1.2.1 
Source: Listing 16.2.8.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.4.1.2.2 Summary of Hematology and Coagulation Shifts from Baseline MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 52 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Table 14.3.4.2.1.1 Summary of Summary of Chemistry SAD (Safety Population) 
 
 
Parameter: Alanine Aminotransferase (ALT) (unit) 
 
 
 
Actual Value 
 
 
 
Change from Baseline[1] 
 
 
 
Treatment 
 
 
Visit 
 
 
n 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
 
n 
 
 
Mean 
 
 
SD 
 
 
Median 
 
 
Minimum 
 
 
Maximum 
 
CVN766 5 mg (N=xx) 
 
Baseline[1] 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
N/A 
 
 
 
 
 
 
Day 1 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 14/ ET 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
CVN766 15 mg (N=xx) 
 
Baseline[1] 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
N/A 
 
 
 
 
 
 
Day 1 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 14/ ET 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
Xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing 16.2.8.2.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable, SD = Standard Deviation, ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 53 of 126 
 
 
Programing Note: 
Same as Table 14.3.4.2.1.1 
Source: Listing 16.2.8.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
 
Table 14.3.4.2.1.2 Summary of Summary of Chemistry MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 54 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Table 14.3.4.2.2.1 Summary of Chemistry Shifts from Baseline SAD (Safety Population) 
Parameter: Alanine Aminotransferase (ALT) (unit) 
 
 
 
 
 
 
Post-Baseline 
 
 
Treatment 
 
Visit 
 
Visit(n)[2] 
Result 
Classification 
Baseline[1] 
n(%) 
Low 
n(%) 
Normal 
n(%) 
High 
n(%) 
CVN766 5 mg (N=xx) Day 1 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 2 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 3 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
….. 
 
 
 
 
 
 
 
Day 14/ET 
xx 
Low 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
High 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
… 
… 
 
 
 
 
 
Source: Listing 16.2.8.2.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
[2] Number of participants with non-missing values at that visit. 
Participant with both baseline and post-baseline values included. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 55 of 126 
 
 
Programing Note: 
Same as Table 14.3.4.2.2.1 
Source: Listing 16.2.8.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
 
Table 14.3.4.2.2.2 Summary of Chemistry Shifts from Baseline MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 56 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall. 
Overall CVN766 will not contain CVN766 45 mg(Fed). 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort. 
 
Table 14.3.4.3.1 Summary of Urinalysis SAD (Safety Population) 
 
Parameter: Glucose (unit) 
 
 
 
Treatment 
 
 
Visit 
 
 
Visit(n)[2] 
 
 
Normal 
Abnormal, 
Not Clinically 
Significant 
Abnormal, 
Clinically 
Significant 
 
CVN766 5 mg (N=xx) 
 
Baseline 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Day 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
… 
 
 
 
 
CVN766 15 mg (N=xx) 
Baseline 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…. 
Day 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
.. 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Source: Listing 16.2.8.3.1 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 57 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.4.3.2 Summary of Urinalysis MAD (Safety Population) 
 
Parameter: Glucose (unit) 
 
 
 
Treatment 
 
 
Visit 
 
 
Visit(n)[2] 
 
 
Normal 
Abnormal, 
Not Clinically 
Significant 
Abnormal, 
Clinically 
Significant 
 
CVN766 45 mg (N=xx) 
 
Baseline 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Day 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
…… 
 
 
 
 
CVN766 125 mg (N=xx) 
Baseline 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…. 
Day 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Source: Listing 16.2.8.3.2 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
[2] Number of participants with non-missing values at that visit. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 58 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg(Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort 
Repeat for Position: Supine, Standing 
 
Table 14.3.5.1.1 Summary of Vital Signs SAD (Safety Population) 
Position: Supine Measurements 
Parameter: Heart rate (beats/min) 
 
 
 
Actual Value  
 
 
Change from Baseline[1] 
 
 
Treatment 
 
Visit 
 
Timepoint 
 
n 
 
Mean 
 
SD 
 
Median 
 
Minimum 
 
Maximum 
 
n 
 
Mean 
 
SD 
 
Median 
 
Minimum 
 
Maximum 
 
CVN766 5 mg 
(N=xx) 
 
 
Baseline[1] 
 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
 
N/A 
 
 
 
 
 
 
Day 1 
0.5 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
1 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
2 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
4 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
8 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
12 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
24 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
36 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
48 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
60 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
72 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
ET 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
…. 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing 16.2.9.1.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 59 of 126 
 
 
Programing Note: 
Same as Table 14.3.5.1.1 
Source: Listing 16.2.9.1.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
Repeat for Position: Supine, Standing 
 
Table 14.3.5.1.2 Summary of Vital Signs MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 60 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg( Fed) 
Overall Placebo will not contain Placebo (fed) from S3 cohort 
 
Table 14.3.5.2.1 Summary of Orthostatic Vital Signs SAD (Safety Population) 
Parameter: Heart rate (beats/min) 
 
 
 
 
Orthostatic Change 
 
Treatment 
Visit 
Timepoint 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
CVN766 5 mg (N=xx) 
 
 
Baseline[1] 
 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
Day 1 
0.5 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
1 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
2 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
4 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
8 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
12 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
24 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
36 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
48 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
60 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
72 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
ET 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
…. 
…. 
…. 
 
 
 
 
 
Source: Listing 16.2.9.1.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
ET = Early Termination. 
Orthostatic Change = value of parameter in standing – value of parameter in supine. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 61 of 126 
 
 
Programing Note: 
 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
Table 14.3.5.2.2 Summary of Orthostatic Vital Signs MAD (Safety Population) 
Parameter: Heart rate (beats/min) 
 
 
 
 
Orthostatic Change 
 
Treatment 
Visit 
Timepoint 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 
CVN766 45 mg (N=xx) 
 
 
Baseline[1] 
 
 
 
xx 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx 
 
 
xx 
 
Day 1 
0.5 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
1 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
2 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
4 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
8 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
12 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 2 
24 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
36 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
48 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
60 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
72 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
ET 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
…. 
…. 
…. 
 
 
 
 
 
Source: Listing 16.2.9.1.1 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. SD = Standard Deviation. 
ET = Early Termination. 
Orthostatic Change = value of parameter in standing – value of parameter in supine. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 62 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg( Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort 
 
Repeat for Category: Drop in dBP of ≥10mmHg from Supine to Standing, Drop in sBP of ≥20mmHg when moving from supine to standing, Increase in HR 
of ≥30bpm when moving from supine to standing 
 
 
Table 14.3.5.3.1 Summary of Categorical analysis of Orthostatic Vital Signs SAD (Safety Population) 
Category: Drop in dBP of ≥10mmHg from Supine to Standing 
 
 
Visit 
 
 
Timepoint 
TRTA 
N=xxx 
n (%) 
TRTB 
N=xxx 
n (%) 
TRTC 
N=xxx 
n (%) 
 
 
…. 
Day 1 
0.5 hours 
xx 
xx 
xx 
xx 
 
1 hours 
xx 
xx 
xx 
xx 
 
2 hours 
xx 
xx 
xx 
xx 
 
4 hours 
xx 
xx 
xx 
xx 
 
8 hours 
xx 
xx 
xx 
xx 
 
12 hours 
xx 
xx 
xx 
xx 
 
24 hours 
xx 
xx 
xx 
xx 
 
36 hours 
xx 
xx 
xx 
xx 
 
48 hours 
xx 
xx 
xx 
xx 
 
60 hours 
xx 
xx 
xx 
xx 
 
72 hours 
xx 
xx 
xx 
xx 
… 
 
 
 
 
 
Source: Listing 16.2.9.1.1 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 63 of 126 
 
 
Programing Note: 
 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
Repeat for Category: Drop in dBP of ≥10mmHg from Supine to Standing, Drop in sBP of ≥20mmHg when moving from supine to standing, Increase in HR 
of ≥30bpm when moving from supine to standing 
 
Table 14.3.5.3.2 Summary of Categorical analysis of Orthostatic Vital Signs MAD (Safety Population) 
Category: Drop in dBP of ≥10mmHg from Supine to Standing 
 
 
Visit 
 
 
Timepoint 
TRTA 
N=xxx 
n (%) 
TRTB 
N=xxx 
n (%) 
TRTC 
N=xxx 
n (%) 
 
 
…. 
Day 1 
0.5 hours 
xx 
xx 
xx 
xx 
 
1 hours 
xx 
xx 
xx 
xx 
 
2 hours 
xx 
xx 
xx 
xx 
 
4 hours 
xx 
xx 
xx 
xx 
 
8 hours 
xx 
xx 
xx 
xx 
 
12 hours 
xx 
xx 
xx 
xx 
 
24 hours 
xx 
xx 
xx 
xx 
 
36 hours 
xx 
xx 
xx 
xx 
 
48 hours 
xx 
xx 
xx 
xx 
 
60 hours 
xx 
xx 
xx 
xx 
 
72 hours 
xx 
xx 
xx 
xx 
… 
 
 
 
 
 
 
Source: Listing 16.2.9.1.2 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 64 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
 
Table 14.3.5.4.1.1 Summary of 12-Lead ECG SAD (Safety Population) 
 
Parameter: Heart Rate (bpm) 
 
 
 
Actual Value  
 
 
Change from Baseline[1] 
 
 
Treatment 
 
Visit 
 
Timepoint 
 
n 
 
Mean 
 
SD 
 
Median 
 
Minimum 
 
Maximum 
 
n 
 
Mean 
 
SD 
 
Median 
 
Minimum 
 
Maximum 
 
CVN766 5 mg 
(N=xx) 
 
Baseline[1] 
 
 
xx 
 
xx.x 
 
xx.x 
 
xx.x 
 
xx 
 
xx 
 
N/A 
 
 
 
 
 
 
Day 1 
0.5 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
…….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
24 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 4 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 8 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
ET 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
CVN766 15 mg 
(N=xx) 
Baseline[1]  
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
N/A 
 
 
 
 
 
 
Day 1 
0.5 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
 
…….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
24 hours 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
 
Day 3 
 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
xx 
xx.x 
xx.x 
xx.x 
xx 
xx 
…. 
…. 
…. 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing 16.2.9.2.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
For multiple tracings done as part of one assessment, the mean of the three tracings are summarized for each participant. 
N/A = Not Applicable, SD = Standard Deviation, ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 65 of 126 
 
 
Programing Note: 
Same as Table 14.3.5.2.1.1 
Source: Listing 16.2.9.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo and Overall. 
 
 
Table 14.3.5.4.1.2 Summary of 12-Lead ECG MAD (Safety Population) 
 
 
Overall CVN766 will not contain
CVN766 45 mg( Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 Cohort 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 66 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Placebo(Fed) 
and Overall 
Overall CVN766 will not contain CVN766 45 mg( Fed) 
Overall Placebo will not contain Placebo (Fed) from S3 cohort 
 
Table 14.3.5.4.2.1 Summary of 12-Lead ECG Interpretation SAD (Safety Population) 
 
 
 
Treatment 
 
Visit 
 
Visit(n)[2] 
 
Timepoint 
 
Normal 
Abnormal, 
Not Clinically 
Significant 
Abnormal, 
Clinically 
Significant 
 
Not Done 
 
CVN766 5 mg (N=xx) 
 
Baseline[1] 
 
xx 
 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Day 1 
xx 
0.5 hours 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
……… 
 
 
 
 
 
Day 2 
xx 
24 hours 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 3 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 4 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 8 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 14/ ET 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
CVN766 15 mg (N=xx) 
 
Baseline[1] 
 
xx 
 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
xx (xx.x%) 
 
Day 1 
xx 
0.5 hours 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
……….. 
 
 
 
 
 
Day 2 
xx 
24 hours 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 3 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 4 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Day 8 
xx 
 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
…. 
…. 
 
…. 
 
 
 
Source: Listing 16.2.9.2.1 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
Worst of the three tracings are summarized for each participant. 
 
Number of participants at each visit (n) will be used as the denominator for the calculation of all percentages. 
[2] Number of participants with non-missing values at that visit. 
Participant with both baseline and post-baseline values included. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 67 of 126 
 
 
Programing Note: 
Same as Table 14.3.5.4.2.1 
Source: Listing 16.2.9.2.2 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall CVN766, Overall Placebo Overall. 
 
Table 14.3.5.4.2.2 Summary of 12-Lead ECG Interpretation MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 68 of 126 
 
 
Programing Note: 
 
Repeat for following treatments; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.1.1.1 
Repeat for following treatments ; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.1.1.1 Analysis Populations SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
Safety 
Population 
Pharmacokinetic 
Population 
 
XXX 
 
Yes 
 
Yes 
XXX 
Yes 
Yes 
XXX 
Yes 
Yes 
XXX 
No 
No 
…. 
 
 
 
 
 
 
 
Listing 16.2.1.1.2 Analysis Populations MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 69 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.1.2.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.1.2.1 Participant Disposition SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 Informed Consent 
 
 
Re-consent 
 
Study 
Completion/ 
Early 
Termination 
Date 
(YYYY-MM-DD) 
 
 
 
Date for 
Consent 
Withdrawal 
(YYYY-MM- 
DD) 
 
 
Subject ID 
 
Date 
(YYYY-MM- 
DD) 
 
 
Version 
 
Protocol 
Version 
 
Date 
(YYYY-MM- 
DD) 
 
 
Version 
 
Protocol 
Version 
 
Did the Participant 
Complete the Study? 
Primary 
Reason for 
Non- 
completion 
 
Reason for 
Consent 
Withdrawal 
 
XXX 
 
YYYY-MM-DD 
 
1.2 
 
1.2 
 
N/A 
 
 
 
Yes 
 
YYYY-MM-DD 
 
 
 
 
XXX 
 
YYYY-MM-DD 
Other: 
xx.x 
Other: 
xx.x 
 
N/A 
 
 
 
Yes 
 
YYYY-MM-DD 
 
 
 
 
XXX 
 
YYYY-MM-DD 
 
1.2 
 
1.2 
 
YYYY-MM-DD 
Other: 
xx.x 
Other: 
xx.x 
 
No 
 
YYYY-MM-DD 
Withdrawal 
by Subject 
 
xxxxxxxxxxxxxxx 
 
YYYY-MM-DD 
 
XXX 
 
YYYY-MM-DD 
 
1.2 
 
1.2 
 
YYYY-MM-DD 
Other: 
xx.x 
Other: 
xx.x 
 
Yes 
 
YYYY-MM-DD 
 
 
 
…. 
 
 
 
 
 
 
 
 
 
 
 
N/A = Not Applicable. 
 
 
 
 
 
Listing 16.2.1.2.2 Participant Disposition MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 70 of 126 
 
 
Programing Note: 
 
Repeat for following treatments ; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.2.1 
Repeat for following treatments ; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
 
Listing 16.2.2.1 Protocol Deviation SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
Date of Deviation 
(YYYY-MM-DD) 
 
Type of Deviation 
 
Deviation Description 
 
Important Deviation 
 
 
XXX 
 
 
YYYY-MM-DD 
 
 
YYYYYYYYYYYYYYY 
 
 
XXXXXXXXXXXXX 
 
 
No 
XXX 
YYYY-MM-DD 
YYYYYYYYYYYYYYY 
XXXXXXXXXXXXX 
No 
…. 
 
 
 
 
 
 
 
Listing 16.2.2.2 Protocol Deviation MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 71 of 126 
 
 
Programing Note: 
 
Repeat for following treatments; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.1.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.4.1.1 Demographics and Baseline Characteristics SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
Subject ID 
 
Date of 
Birth 
(YYYY-MM-DD) 
Age at 
Informed 
Consent 
(years) 
 
 
Sex 
 
Childbearing 
Potential[1] 
 
Reason not of 
Childbearing 
Potential 
 
Smoking 
Status 
 
 
Race 
 
 
Ethnicity 
 
Height at 
screening 
(cm) 
 
Weight at 
screening 
(kg) 
Body Mass 
Index at 
screening 
(kg/m2) 
 
 
XXX 
 
 
YYYY-MM-DD 
 
 
xx 
 
 
Female 
 
 
No 
 
 
Other - xxxxxxx 
 
 
Yes 
 
 
Asian 
 
 
xxxxx 
 
 
xxx 
 
 
xx.x 
 
 
xx.x 
XXX 
YYYY-MM-DD 
xx 
Male 
N/A 
 
No 
Asian 
xxxxx 
xxx 
xx.x 
xx.x 
…. 
 
 
 
 
 
 
 
 
 
 
 
N/A = Not Applicable. 
[1] only for female participants. 
 
 
Listing 16.2.4.1.2 Demographics and Baseline Characteristics MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 72 of 126 
 
 
Programing Note: 
 
Repeat for following treatments; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.2.1 
 
Repeat for following treatments; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
Listing 16.2.4.2.1 Medical/Surgical History SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
Subject ID 
 
 
Medical History Term/ System Organ Class /Preferred Term 
 
Start Date 
(YYYY-MM-DD) 
 
End Date 
(YYYY-MM-DD) 
Is the Subject 
currently taking 
medication for this 
condition? 
 
XXX 
 
XXXXXXXXXX/ YYYYYYYYY/ ZZZZZZZZZ 
 
YYYY-MM-DD 
 
YYYY-MM-DD 
 
Xxx 
 
XXXXXXXXXX/ YYYYYYYYY/ ZZZZZZZZZ 
YYYY-MM-DD 
Ongoing 
xxx 
….. 
 
 
 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
Listing 16.2.4.2.2 Medical/Surgical History MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 73 of 126 
 
 
Programing Note: 
Repeat for following treatments; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall Placebo. 
Programing Note: 
Same as Listing 16.2.4.3.1 
Repeat for following treatments; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg, Overall Placebo. 
 
 
 
Listing 16.2.4.3.1 Hepatitis Panel SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
 
Visit 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
 
Test Name 
 
Result 
 
 
XXX 
 
 
Screening 
 
 
YYYY-MM-DD/ HH:MM 
 
 
Hepatitis B Surface Antigen (HBsAg) 
 
 
Negative 
 
 
 
Hepatitis C Antibody (HCVAb) 
Negative 
 
 
 
HIV-1 Antibody/HIV-2 Antibody 
Negative 
….. 
 
 
 
 
 
 
 
 
Listing 16.2.4.3.2 Hepatitis Panel MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 74 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.4.1 
Repeat for following treatments; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.4.4.1 Alcohol Breath Test SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
 
Was Alcohol (Breath Test) 
Performed? 
(Yes/No – Reason) 
 
 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
 
 
Result 
Subject ID 
Visit 
 
 
 
XXX 
 
 
Screening 
 
 
Yes 
 
 
YYYY-MM-DD/ HH:MM 
 
 
xxxx 
XXX 
Screening 
No- xxxx 
YYYY-MM-DD/ HH:MM 
xxxx 
….. 
 
 
 
 
 
 
 
Listing 16.2.4.4.2 Alcohol Breath Test SAD MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 75 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.5.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.4.5.1 Urine Drug Screen SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
 
 
Subject ID 
 
 
 
 
Visit 
Was subject 
abstained from 
caffeine 
consumption 
since 
24hrs? (Yes/No) 
 
Was Urine Drug 
Screen Test 
performed? 
(Yes/No- 
Reason) 
 
Collection 
Date/ Time 
(YYYY-MM-DD/ 
HH:MM) 
 
 
 
 
Test Name 
 
 
 
 
Result 
 
 
XXX 
 
 
Screening 
 
 
 
YYYY-MM-DD/ 
HH:MM 
 
 
…. 
 
 
Negative 
 
 
 
 
 
…. 
Negative 
 
 
 
 
 
…. 
Negative 
….. 
 
 
 
 
 
 
 
 
 
 
Listing 16.2.4.5.2 Urine Drug Screen MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 76 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.6.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.4.6.1 Follicle-Stimulating Hormone Test SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
 
Visit 
Collection Date/ Time 
(YYYY-MM-DD/ HH:MM) 
 
Was Sample collected For FSH Test 
 
Result (unit) 
 
 
XXX 
 
 
Screening 
 
 
YYYY-MM-DD/ HH:MM 
 
 
Yes 
 
 
 
 
Yes 
 
 
 
 
No 
 
….. 
 
 
 
 
 
 
 
Listing 16.2.4.6.2 Follicle-Stimulating Hormone Test MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 77 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.7.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
Listing 16.2.4.7.1 Pregnancy Test SAD (Safety Population) 
Treatment: CVN766 5 mg 
 
 
Subject ID 
 
Visit 
Was Sample Collected for 
Pregnancy test? (Yes/No) 
Assessment 
Date/ Time 
(YYYY-MM-DD/ HH:MM) 
 
Type of test 
 
Result 
 
 
XXX 
 
 
Screening 
 
 
 
YYYY-MM-DD/ HH:MM 
 
 
xx 
 
 
Xx 
…. 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
ET = Early Termination 
 
 
Listing 16.2.4.7.2 Pregnancy Test MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 78 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.4.8.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.4.8.1 Eligibility Criteria SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
 
Visit 
 
Participant Eligible 
Category Failed 
(Inclusion/ Exclusion) 
Inclusion/ Exclusion 
Criterion not met 
 
XXX 
 
Screening 
 
No 
 
Inclusion and Exclusion 
 
Exclusion: xx, xx; Inclusion xx, xx 
 
Day -2 
Yes 
 
 
 
Day -1 
Yes 
 
 
…. 
…. 
 
 
 
 
 
 
Listing 16.2.4.8.2 Eligibility Criteria MAD (Safety Population) 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 79 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.5.1.1 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.5.1.1 Participant Randomization SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
Randomization Date 
(YYYY-MM-DD) 
Randomization 
Number 
Randomized Treatment 
Received 
 
XXX 
 
YYYY-MM-DD 
 
XXX 
 
… 
XXX 
YYYY-MM-DD 
XXX 
… 
XXX 
YYYY-MM-DD 
XXX 
… 
…. 
 
 
 
 
 
 
Listing 16.2.5.1.2 Participant Randomization MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 80 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.5.2.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.5.2.1 Study Drug Administration SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
Subject ID 
 
Visit 
Study Drug 
Administered/ No - 
Reason 
Date/ Time of 
Administration 
(YYYY-MM-DD/ HH:MM) 
Dose 
(mg) 
Was the full 
dose administered? 
Was study drug 
given as per 
protocol? 
Was subject 
fasting? 
 
XXX 
 
Day 1 
 
Yes 
 
YYYY-MM-DD/ HH:MM 
 
xx 
 
Yes 
 
Yes 
 
Yes 
 
Day 2 
Yes 
YYYY-MM-DD/ HH: MM 
xx 
Yes 
Yes 
Yes 
 
Day 3 
No - xxxxxxxx 
 
 
 
 
 
... 
…… 
 
 
 
 
 
 
 
 
 
Listing 16.2.5.2.2 Study Drug Administration MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 81 of 126 
 
 
Programing Note: 
Add following treatment; 
CVN766 45 mg 
 
 
Listing 16.2.5.3.1 Meal Records SAD (Safety Population) 
 
Treatment: CVN766 45 mg 
 
 
 
Subject ID 
 
 
Visit 
Study Meal 
Administered/ No - 
Reason 
Date/ Time of 
Administration 
(YYYY-MM-DD/ HH:MM) 
 
Was full 
meal consumed? 
 
Percentage 
consumed (%) 
Reason full 
meal not 
consumed 
 
XXX 
 
Day 1 
 
Break fast 
 
YYYY-MM-DD/ HH:MM 
 
Yes 
 
xx 
 
xx 
 
Day 1 
Lunch 
YYYY-MM-DD/ HH:MM 
Yes 
xx 
xx 
 
Day 1 
Dinner 
YYYY-MM-DD/ HH:MM 
Yes 
xx 
xx 
 
Day 1 
Snack 
YYYY-MM-DD/ HH:MM 
Yes 
xx 
xx 
 
Day 2 
Break fast 
YYYY-MM-DD/ HH: MM 
Yes 
xx 
xx 
... 
…… 
 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 82 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg 
 
Listing 16.2.6.1.1 Plasma Concentrations for CVN766 SAD (PK Population) 
Analyte XXX (Unit) 
Treatment: CVN766 5 mg 
 
 
 
 
Was 
 
 
 
 
 
 
 
Pharmacokinetic  
 
 
 
 
 
 
Sample 
Date and Time of 
 
 
 
 
 
 
Collected – 
Pharmacokinetic Sample  
 
 
 
 
 
Reason Not 
Collection 
Actual 
Time Deviation 
Concentration 
Subject ID 
Visit 
Timepoint 
Collected 
(YYYY-MM-DD/ HH:MM) 
Time (h) 
(h) 
(unit) 
 
XXX 
 
Day 1 
 
Pre-Dose 
 
Yes 
 
YYYY-MM-DD/ HH:MM 
 
xx.xx 
 
xx.xx 
 
xxx 
 
 
30 minutes 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
1 hour 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
1.5 hour 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
2 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
3 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
5 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
8 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
12 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
16 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
24 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
36 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
48 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
72 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
XXX 
Day 1 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
… 
… 
…. 
 
 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 83 of 126 
 
 
 
Listing 16.2.6.1.2 Plasma Concentrations for CVN766 MAD (PK Population) 
 
 
 
 
Was 
 
 
 
 
 
 
 
Pharmacokinetic  
 
 
 
 
 
 
Sample 
Date and Time of 
 
 
 
 
 
 
Collected – 
Pharmacokinetic Sample  
 
 
 
 
 
Reason Not 
Collection 
Actual 
Time Deviation 
Concentration 
Subject ID 
Visit 
Timepoint 
Collected 
(YYYY-MM-DD/ HH:MM) 
Time (h) 
(h) 
(unit) 
 
XXX 
 
Day 1 
 
Pre-Dose 
 
Yes 
 
YYYY-MM-DD/ HH:MM 
 
xxx.xx 
 
xx.xx 
 
xxx 
 
 
30 minutes 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
1 hour 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
1.5 hour 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
2 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
3 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
5 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
8 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
12 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
16 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
Day 2 
24 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
Day 3 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
Day 4 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
Day 5 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
Day 6 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
Day 7 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
30 minutes 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
1 hour 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
1.5 hour 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
2 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
3 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
5 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
8 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
12 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
16 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
24 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
36 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
48 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
 
 
72 hours 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
XXX 
Day 1 
Pre-Dose 
Yes 
YYYY-MM-DD/ HH:MM 
xxx.xx 
xx.xx 
xxx 
… 
… 
…. 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 84 of 126 
 
 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 85 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 45 mg 
 
 
 
Listing 16.2.6.2.1 Urine Concentration of CVN766 MAD (PK Population) 
Analyte XXX (Unit) 
Treatment: CVN766 45 mg 
 
 
 
 
 
Subject 
ID 
 
 
 
 
 
Visit 
 
 
 
 
 
Timepoint 
Was PK 
Urine 
Sample 
Collected 
– Reason 
Not 
Collected 
 
Start Date/ 
Time of 
Collection 
(YYYY-MM-DD/ 
HH:MM) 
 
End Date / 
Time of 
Collection 
(YYYY-MM-DD/ 
HH:MM) 
 
 
Duration 
of 
Sample 
(hours) 
 
 
Total 
Volume 
Collected 
(mL) 
 
 
 
 
Concentration 
(unit) 
 
 
Urine 
Excretion 
(Ae) 
(unit) 
 
Reason for 
Exclusion 
from Summary 
of Urine 
XXXXXXXX 
Excretion 
 
 
XXX 
 
 
Day 1 
 
 
Pre-Dose 
 
 
Yes 
 
YYYY-MM-DD/ 
HH:MM 
 
YYYY-MM-DD/ 
HH:MM 
 
 
xx 
 
 
xxx.xx 
 
 
xxx 
 
 
xx.xx 
 
 
 
0-6 Hours 
No: 
Reason 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
xx 
xxx.xx 
xxx 
xx.xx 
 
 
 
6-12 
Hours 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
12-24 
Hours 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
Day 7 
 
0-6 Hours 
No: 
Reason 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
6-12 
Hours 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
12-24 
Hours 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
XXX 
 
Day 1 
 
Pre-Dose 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
 
0-6 Hours 
No: 
Reason 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
6-12 
Hours 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
 
 
12-24 
Hours 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
YYYY-MM-DD/ 
HH:MM 
 
xx 
 
xxx.xx 
 
xxx 
 
xx.xx 
 
… 
… 
 
 
 
 
 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 86 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
 
Analyte XXX (Unit) 
Treatment: CVN766 5 mg 
Listing 16.2.6.3.1 PK Plasma Parameters for CVN766 SAD (Pharmacokinetic Population) 
 
 
 
Subject ID 
 
 
Visit 
 
Cmax 
(unit) 
 
tmax 
(unit) 
 
 
Tlast 
 
AUCt 
(unit) 
 
AUC24 
unit) 
 
AUCinf 
(unit) 
 
 
%AUCext 
 
t½ 
(unit) 
 
 
λz 
 
CL/F 
(unit) 
 
VZ/F 
(unit) 
 
CSF:Plasma 
ratio 
 
 
DN_Cmax 
 
 
DN_AUC24hr 
 
 
DN_AUCt 
 
 
DN_AUCinf 
 
 
XXX 
 
 
Day 1 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
XXX 
Day 1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analyte XXX (Unit) 
Treatment: CVN766 45 mg 
Visit: Day 1 
 
Listing 16.2.6.3.2 PK Plasma Parameters for CVN766 MAD (Pharmacokinetic Population) 
 
 
 
Subject ID 
 
 
Visit 
 
Cmax 
(unit) 
 
Cmin 
(unit) 
 
Ctrough 
(unit) 
 
tmax 
(unit) 
 
tmin 
(unit) 
 
AUCt 
(unit) 
 
AUC24 
unit) 
 
CSF:Plasma 
ratio 
 
 
DN_Cmax 
 
 
DN_AUC24hr 
 
 
DN_AUCt 
 
 
XXX 
 
 
Day 1 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
XXX 
Day 1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
…. 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 87 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Analyte XXX (Unit) 
Treatment: CVN766 45 mg 
Visit: Day 7 
 
 
Subjec 
t ID 
 
Visi 
t 
 
Cmax,ss 
(unit 
) 
 
Cmix,ss 
(unit 
) 
 
Ctrough 
(unit 
) 
 
Cavg,ss 
(unit 
) 
 
Tmax,ss 
(unit 
) 
 
Tmin,ss 
unit 
) 
 
AUCt 
(unit 
) 
 
AUCtau 
(unit 
) 
 
AUCinf 
(unit 
) 
 
λz 
(unit 
) 
 
CLss/F,s 
s 
(unit) 
 
VZ,ss/F,s 
s 
(unit) 
 
RACma 
x 
 
 
RAAUC 
 
CSF:Plasm 
a ratio 
 
DN_Cmax,s 
s 
 
DN_AUC24h 
r 
 
DN_AUC 
t 
 
DN_AUC 
t 
 
 
XXX 
 
Day 
1 
Day 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
xx. 
x 
xx. 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x xx.x xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 88 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
 
 
Listing 16.2.6.4.1 PK Urine Parameters for CVN766 MAD (Pharmacokinetic Population) 
 
Analyte XXX (Unit) 
Treatment: CVN766 45 mg 
Visit: Day 1 
 
 
 
Subject ID 
 
 
Visit 
 
Aet1-t2 
(unit) 
 
 
Fet1-t2 (unit) 
 
CLr 
(unit) 
 
 
XXX 
 
 
Day 1 
 
 
xx.x 
 
 
xx.x 
 
 
xx.x 
XXX 
Day 1 
xx.x 
xx.x 
xx.x 
…. 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 89 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 45 mg (Fasted). 
 
Listing 16.2.6.5.1 CSF Concentration SAD (Pharmacokinetic Population) 
 
 
 
Subject ID 
 
 
 
Visit 
Was PK CSF 
Sample 
Collected – 
Reason Not 
Collected 
Scheduled Date/ 
Time of 
Collection 
(YYYY-MM-DD/ 
HH:MM) 
 
 
 
Actual Time (h) 
 
 
Time Deviation 
(h) 
 
 
CSF : Plasma 
ratio 
 
 
Concentration 
(unit) 
 
 
XXX 
 
 
Day 1 
 
 
Yes 
 
YYYY-MM-DD/ 
HH:MM 
 
 
xxx.xx 
 
 
xxx.x 
 
 
xxx 
 
 
xxx 
 
 
No: Reason 
 
 
 
 
 
 
XXX 
 
Day 1 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
 
xxx.xx 
 
xx.xx 
 
xxx 
 
xxx 
 
 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
 
xxx.xx 
 
xx.xx 
 
xxx 
 
xxx 
… 
… 
 
xxx.xx 
xx.xx 
xxx 
xxx 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 90 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
Listing 16.2.6.5.2 CSF Collection MAD (Pharmacokinetic Population) 
 
 
 
 
Subject ID 
 
 
 
Visit 
Was PK CSF 
Sample 
Collected – 
Reason Not 
Collected 
Scheduled Date/ 
Time of 
Collection 
(YYYY-MM-DD/ 
HH:MM) 
 
 
 
Actual Time (h) 
 
 
Time Deviation 
(h) 
 
 
 
CSF: Plasma ratio 
 
 
Concentration 
(unit) 
 
 
XXX 
 
 
Day 1 
 
 
Yes 
 
YYYY-MM-DD/ 
HH:MM 
 
 
xxx.xx 
 
 
xxx.x 
 
 
xxx 
 
 
xxx 
 
 
No: Reason 
 
 
 
 
 
 
Day 7 
 
 
 
 
xxx 
xxx 
 
XXX 
 
Day 1 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
 
xxx.xx 
 
xx.xx 
 
xxx 
 
xxx 
 
 
 
Yes 
YYYY-MM-DD/ 
HH:MM 
 
xxx.xx 
 
xx.xx 
 
xxx 
 
xxx 
… 
… 
 
xxx.xx 
xx.xx 
xxx 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 91 of 126 
 
 
Programing Note: 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.6.6.1 CV Telemetry SAD (Pharmacokinetic Population) 
 
Treatment: CVN766 5 mg 
Test: CV Telemetry 
 
 
 
Subject ID 
 
 
 
Visit 
 
 
 
Time Point 
Were CV 
Telemetry 
performed? 
if No- 
reason 
Start Date/time 
of Monitoring 
(YYYY-MM-DD/ 
HH:MM) 
 
End Date/time 
of Monitoring 
 
(YYYY-MM-DD/ HH:MM) 
 
 
Assessment 
Value 
 
 
Abnormality 
Description 
 
XXX 
 
Screening 
 
 
Yes 
 
YYYY-MM-DD/ HH:MM 
 
YYYY-MM-DD/ HH:MM 
 
Normal 
 
 
Day -1 
 
 
YYYY-MM-DD/ HH:MM 
YYYY-MM-DD/ HH:MM 
Abnormal CS 
xxxx 
 
Day 1 
4 hours post-dose 
Yes 
YYYY-MM-DD/ HH:MM 
YYYY-MM-DD/ HH:MM 
xx 
 
 
 
8 hours post-dose 
Yes 
YYYY-MM-DD/ HH:MM 
YYYY-MM-DD/ HH:MM 
xx 
 
 
Day 2 
24 hours post-dose 
Yes 
YYYY-MM-DD/ HH:MM 
YYYY-MM-DD/ HH:MM 
xx 
 
…. 
 
 
 
 
 
 
N/A = Not Applicable. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 92 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.7.1.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.7.1.1 Adverse Events SAD (Safety Population) 
 
Treatment CVN766 5 mg 
 
 
 
Adverse Event 
Verbatim/ 
System Organ 
Class/ 
Preferred Term 
Start 
Date/ 
Time/ 
(YYYY- 
MM-DD/ 
HH:MM) 
 
End 
Date/ 
Time/ 
(YYYY- 
MM-DD) 
Pre- 
treatment 
event? 
 
 
 
 
 
 
 
 
 
Subject 
ID 
 
Severity 
 
SAE/ Reason 
Relationship 
to Study 
Treatment 
 
Action 
Taken 
Concomitant 
Medication/ 
Other Action 
 
Outcome 
Subject 
Discontinued 
due to AE 
 
TEAE 
 
XXX 
 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
 
YYYY- 
MM-DD/ 
HH:MM 
 
YYYY-MM- 
DD/ 
HH:MM 
 
No 
 
Mild 
 
Yes/Death 
 
Related 
 
N/A 
 
Yes, CM1/No 
 
Recovered/ 
Resolved 
 
No 
 
Yes 
 
XXX 
 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
 
YYYY- 
MM-DD/ 
HH:MM 
 
YYYY-MM- 
DD/ 
HH:MM 
 
 
Mild 
 
Yes/hospitalization 
 
Unrelated 
 
Dose 
not 
changed 
 
No/ Yes, 
CM1/No 
 
Recovering / 
Resolving 
 
No 
 
Yes 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
SAE = Serious Adverse Event. TEAE = A treatment-emergent adverse event. 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
Listing 16.2.7.1.2 Adverse Events MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 93 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.7.2.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
Listing 16.2.7.2.1 Serious Adverse Events SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
SAE Reason: Hospitalization 
 
 
 
 
Subject 
ID 
 
 
Adverse Event 
Verbatim/ 
System Organ Class/ 
Preferred Term 
Start 
Date/ 
Time/ 
(YYYY- 
MM-DD/ 
HH:MM) 
 
 
 
End Date/ 
Time/ 
(YYYY-MM-DD) 
 
 
 
 
Severity 
 
 
 
SAE/ 
Reason 
Relatio 
nship 
to 
Study 
Treatme 
nt 
 
 
 
Action 
Taken 
 
 
 
Concomitant 
Medication/ 
Other Action 
 
 
 
 
Outcome 
 
 
 
Subject 
Discontinued due 
to AE 
 
 
 
 
TEAE 
 
XXX 
 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
 
YYYY-MM- 
DD/ 
HH:MM 
 
YYYY-MM-DD/ 
HH:MM 
 
Mild 
(Grade 1) 
 
… 
 
Related 
 
N/A 
 
Yes, CM1/No 
 
Recovered/ 
Resolved 
 
No 
 
Yes 
 
XXX 
 
XXXXXXXXXXXXXXXXXX 
ZZZZZZZZZZZZZZZZZZ 
YYYYYYYYYYYYYYYYYY 
 
YYYY-MM- 
DD/ 
HH:MM 
 
YYYY-MM-DD/ 
HH:MM 
 
Mild 
(Grade 1) 
 
… 
 
Unrelat 
ed 
 
Dose not 
changed 
 
No/ Yes, CM1/No 
 
Recovering / 
Resolving 
 
No 
 
Yes 
…. 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAE = Serious Adverse Event. TEAE = A treatment-emergent adverse event. 
Medical Dictionary for Regulatory Activities (MedDRA) Version xx.x 
 
 
 
 
Listing 16.2.7.2.2 Serious Adverse Events MAD (Safety Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 94 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.8.1.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.8.1.1 Hematology and Coagulation SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
Lab Category: Hematology 
Parameter: Hemoglobin (unit) 
 
 
 
Subject ID 
 
 
Visit 
Collection 
Date/ Time 
(YYYY-MM-DD/ HH:MM) 
 
Actual 
Value 
 
Change from 
Baseline[1] 
 
Reference 
Range 
 
High/Low 
Flag 
 
Clinically 
Significant 
 
 
XXX 
 
 
Screening 
 
 
YYYY-MM-DD/ HH:MM 
 
 
xx 
 
 
N/A 
 
 
xx, xx 
 
 
 
Day -1 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
xx, xx 
H 
NCS 
 
Day 1 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
Day 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
Day 3 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
… 
 
 
 
 
 
 
…. 
Day 14/ET 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. H = Above Normal Range, L = Below Normal Range. CS = Clinically Significant, NCS = Not Clinically Significant. 
ET = Early Termination. 
 
 
Listing 16.2.8.1.2 Hematology and Coagulation MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 95 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.8.2.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.8.2.1 Serum Chemistry SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
Parameter: Sodium (unit) 
 
Subject ID 
 
Visit 
Collection 
Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline[1] 
Reference 
Range 
High/Low 
Flag 
Clinically 
Significant 
 
Comments 
 
 
XXX 
 
 
Screening 
 
 
YYYY-MM-DD/ HH:MM 
 
 
xx 
 
 
N/A 
 
 
xx, xx 
 
 
 
 
Day -1[1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
xx, xx 
H 
NCS 
xxxxxxxx 
 
Day 1 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
 
Day 2 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
 
Day 3 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
 
… 
 
 
 
 
 
 
 
…. 
Day 14/ET 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx, xx 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. H = Above Normal Range, L = Below Normal Range. CS = Clinically Significant, NCS = Not Clinically Significant. 
ET = Early Termination. 
 
 
 
Listing 16.2.8.2.2 Serum Chemistry MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 96 of 126 
 
 
 
Listing 16.2.8.3.1 Urinalysis SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
Parameter: Glucose (unit) 
 
Subject ID 
 
Visit 
Collection 
Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Reference 
Range 
Abnormal 
Flag 
Clinically 
Significant 
 
 
XXX 
 
 
Day -1[1] 
 
 
YYYY-MM-DD/ HH:MM 
 
 
Trace 
 
xx, xx 
 
 
Abnormal 
 
 
NCS 
 
Day 7 
YYYY-MM-DD/ HH:MM 
xxxxxxx 
xx, xx 
 
NCS 
…. 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
H = Above Normal Range, L = Below Normal Range. CS = Clinically Significant, NCS = Not Clinically Significant. 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 97 of 126 
 
 
Programing Note: 
Same as Listing 16.2.8.3.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.8.3.2 Urinalysis MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 98 of 126 
 
 
Programing Note: 
 
Add following treatment columns; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Repeat for: Supine, Standing. 
 
Listing 16.2.9.1.1 Vital Signs SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
Parameter: Heart Rate (bpm) 
Test: Supine 
 
 
Subject ID 
 
Visit 
 
Time Point 
Assessment 
Date/ Time 
(YYYY-MM-DD/ HH:MM) 
Actual 
Value 
Change from 
Baseline[1] 
Vital Signs 
Assessment 
 
 
XXX 
 
 
Screening 
 
 
 
YYYY-MM-DD/ HH:MM 
 
 
xx 
 
 
N/A 
 
 
xx 
 
Day -1 
 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
xx 
 
Day 1 
Pre-Dose [1] 
YYYY-MM-DD/ HH:MM 
xx 
N/A 
xx 
…. 
 
0.5 hour 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
 
1 hour 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
 
2 hours 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
 
4 hours 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
 
6 hours 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
 
8 hours 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
 
12 hours 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
Day 2 
 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
Day 3 
 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
Day 4 
 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
Day 8 
 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
 
/ET 
 
YYYY-MM-DD/ HH:MM 
xx 
xx 
xx 
…. 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 99 of 126 
 
 
Programing Note: 
Same as Listing 16.2.9.1.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Repeat for: Supine, Standing. 
 
Listing 16.2.9.1.2 Vital Signs - MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 100 of 126 
 
 
Programing Note: 
Add following treatment; 
 
Listing 16.2.9.2.1 12-Lead ECG SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
Parameter: QTcF (msec) 
 
 
 
 
Subject ID 
 
 
Visit 
 
 
Time Point 
 
 
Tracing 
Assessment 
Date/ Time 
(YYYY-MM-DD/ 
HH:MM) 
 
 
Actual Value 
 
Average 
value 
 
Change from 
Baseline[1] 
 
Overall ECG 
Clinical 
Interpretation 
 
 
Abnormal Description 
 
XXX 
 
Screening 
 
 
 
YYYY-MM-DD/ HH:MM 
 
xx 
 
 
N/A 
 
Normal 
 
 
Day -1 
 
 
YYYY-MM-DD/ HH:MM 
xx 
 
N/A 
Normal 
 
 
Day 1 
Pre-Dose[1] 
1 
YYYY-MM-DD/ HH:MM 
xx 
xx 
N/A 
Abnormal, NCS 
xxxxxxxxxxx 
 
 
 
2 
YYYY-MM-DD/ HH:MM 
xx 
 
 
Normal 
 
 
 
 
3 
YYYY-MM-DD/ HH:MM 
xx 
 
 
Abnormal, CS 
xxxxxxxxxxx 
 
 
 
0.5 hours 
 
1 
 
YYYY-MM-DD/ HH:MM 
 
xx 
 
xx 
 
xx 
 
Normal 
 
 
 
 
2 
YYYY-MM-DD/ HH:MM 
xx 
 
 
 
 
 
 
 
3 
YYYY-MM-DD/ HH:MM 
xx 
 
 
 
 
 
…. 
 
 
1 hour 
 
1 
 
YYYY-MM-DD/ HH:MM 
 
xx 
 
xx 
 
xx 
 
Normal 
 
 
 
 
2 
YYYY-MM-DD/ HH:MM 
xx 
 
xx 
Normal 
 
 
 
 
3 
YYYY-MM-DD/ HH:MM 
xx 
 
xx 
Normal 
 
 
 
………. 
 
YYYY-MM-DD/ HH:MM 
xx 
 
xx 
Normal 
 
 
 
Day 2 
 
 
 
YYYY-MM-DD/ HH:MM 
 
xx 
 
xx 
 
xx 
 
Normal 
 
 
… 
 
 
YYYY-MM-DD/ HH:MM 
xx 
 
xx 
Normal 
 
 
Day 14/ET  
 
YYYY-MM-DD/ HH:MM 
xx 
 
xx 
Normal 
 
…. 
 
 
 
 
 
 
 
 
 
[1] Baseline is defined as the last available, valid, non-missing observation prior to first study drug administration. 
[2] Mean value of ECG tracings at the timepoint. The worst of the ECG clinical interpretations will be presented with the mean value. 
N/A = Not Applicable. CS = Clinically Significant, NCS = Not Clinically Significant. 
ET = Early Termination. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 101 of 126 
 
 
Programing Note: 
Same as Listing 16.2.9.2.1 
Add following treatment columns; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Display all ECG parameter. 
 
 
 
Listing 16.2.9.2.2 12-Lead ECG MAD (Safety Population) 
 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed),
CVN766 125 mg, CVN766 250 mg. 
Display all ECG parameter. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 102 of 126 
 
 
Programing Note: 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.9.3.1 Neurological Exam SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
Subject ID 
 
 
Visit 
 
Was the Neurological Exam 
performed? (Yes/No – 
Reason) 
Date/ Time of 
Examination 
(YYYY-MM-DD/ 
HH:MM) 
 
 
Body System 
 
 
Result 
 
XXX 
 
Day -1 
 
Yes 
 
YYYY-MM-DD/ 
HH:MM 
 
Light Touch/ Power in Limbs/ Brief 
Cranial Nerve Examination 
 
Normal/ Abnormal NCS/ 
Abnormal CS/ Not Done 
 
Day 1 
Yes 
YYYY-MM-DD/ 
HH:MM 
… 
xx 
 
Day 2 
No – xxx 
YYYY-MM-DD/ 
HH:MM 
… 
xx 
 
Day 3 
… 
YYYY-MM-DD/ 
HH:MM 
… 
xx 
 
Day 4 
…. 
YYYY-MM-DD/ HH: 
MM 
…. 
xx 
... 
…… 
 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 103 of 126 
 
 
Programing Note: 
Same as Listing 16.2.9.3.1 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.9.3.2 Neurological Exam MAD (Safety Population) 
 
 
 
Subject ID 
 
 
Visit 
 
Was the Neurological Exam 
performed? (Yes/No – 
Reason) 
Date/ Time of 
Examination 
(YYYY-MM-DD/ 
HH:MM) 
 
 
Body System 
 
 
Result 
 
XXX 
 
Day -1 
 
Yes 
 
YYYY-MM-DD/ 
HH:MM 
 
Light Touch/ Power in Limbs/ Brief 
Cranial Nerve Examination 
 
Normal/ Abnormal NCS/ 
Abnormal CS/ Not Done 
 
Day 1 
Yes 
YYYY-MM-DD/ 
HH:MM 
… 
xx 
 
Day 7 
No – xxx 
YYYY-MM-DD/ 
HH:MM 
… 
xx 
 
Day 9 
… 
YYYY-MM-DD/ 
HH:MM 
… 
xx 
 
Day 14 
…. 
YYYY-MM-DD/ HH: 
MM 
…. 
xx 
 
E/T 
 
 
 
 
…. 
…. 
…. 
 
 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 104 of 126 
 
 
Programing Note: 
Type = Complete Physical Examination and Symptom-directed Physical Examination 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.9.4.1 Physical Examination SAD (Safety Population) 
Treatment: CVN766 5 mg 
 
 
Subject ID 
 
Visit 
Assessment Date 
(YYYY-MM-DD) 
 
Exam Type/Body System 
 
Result 
 
Description of Abnormality 
 
XXX 
 
Screening 
 
YYYY-MM-DD 
 
Complete Physical examination 
 
 
 
 
 
Head, Eyes, Ears, Nose, Throat 
Normal 
 
 
 
 
Respiratory 
Normal 
 
 
 
 
… 
Normal 
 
 
 
 
Respiratory 
Normal 
 
 
 
 
Other - XXXXXXXX 
Normal 
 
 
 
………. 
 
 
 
 
XXX 
Day 1 
YYYY-MM-DD 
Symptom Directed Physical Examination 
 
 
 
 
 
…Respiratory 
Normal 
 
 
 
 
….. 
 
 
 
……. 
 
 
 
 
 
Day 14/ ET 
YYYY-MM-DD 
Symptom Directed Physical Examination 
 
 
 
 
General Appearance 
Normal 
 
 
 
Head and Neck 
Normal 
 
 
 
Eyes/Ears/Nose/Throat 
Normal 
 
 
 
… 
 
 
 
 
Respiratory 
Abnormal, NCS 
ZZZZZZZZZZZZ 
 
 
Other - XXXXXXXX 
Normal 
 
… 
 
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant. 
ET = Early Termination 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 105 of 126 
 
 
Programing Note: 
Same as Listing 16.2.9.4.1 
Repeat for following treatments; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.9.4.2 Physical Examination MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 106 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Listing 16.2.10.1.1 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
 
Listing 16.2.10.1.1 Prior Medication SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
 
Subject ID 
 
Concomitant Medication Therapy/ 
Anatomical Therapeutic Class (ATC) 
[Level 3]/ 
Preferred Term (PT) 
 
 
Active 
Ingredients 
 
 
 
Indication 
Start Date 
(YYYY-MM-DD) 
End Date 
(YYYY-MM-DD) 
 
 
 
Dose 
 
 
 
Unit 
 
 
 
Frequency 
 
 
 
Route 
 
 
XXX 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
 
xxxxxxxx, 
yyyyyyyy 
 
 
zzzzzzzz 
 
YYYY-MM-DD/ 
YYYY-MM-DD 
 
 
XX 
 
 
Unit 
 
 
YYYYYY 
 
 
ZZZZZ 
 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
 
xxxxxxxx, 
yyyyyyyy 
 
 
zzzzzzzz 
 
YYYY-MM-DD/ 
YYYY-MM-DD 
 
 
XX 
 
 
Unit 
 
 
YYYYYY 
 
 
ZZZZZ 
… 
… 
 
 
 
 
 
 
 
 
 
Prior medications are defined as any medication where the use was stopped prior to the first administration of the study medication. 
World Health Organization-Drug Dictionary (WHO-DD) Version xx, YYYY 
 
 
Listing 16.2.10.1.2 Prior Medication MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 107 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.10.2.1 Concomitant Medication SAD (Safety Population) 
 
Treatment: CVN766 5 mg 
 
 
 
 
Subject ID 
 
Concomitant Medication Therapy/ 
Anatomical Therapeutic Class (ATC) 
[Level 3]/ 
Preferred Term (PT) 
 
 
Active 
Ingredients 
 
 
 
Indication 
Start Date 
(YYYY-MM-DD) 
End Date 
(YYYY-MM-DD) 
 
 
 
Dose 
 
 
 
Unit 
 
 
 
Frequency 
 
 
 
Route 
 
 
XXX 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
 
xxxxxxxx, 
yyyyyyyy 
 
 
zzzzzzzz 
 
YYYY-MM-DD/ 
YYYY-MM-DD 
 
 
XX 
 
 
Unit 
 
 
YYYYYY 
 
 
ZZZZZ 
 
XXXXXXXXXXXXXXXXXXXXXX/ 
ZZZZZZZZZZZZZZZZZZZZZZ/ 
YYYYYYYYYYYYYYYYYYYYYY 
 
xxxxxxxx, 
yyyyyyyy 
 
 
zzzzzzzz 
 
YYYY-MM-DD/ 
Ongoing 
 
 
XX 
 
 
Unit 
 
 
YYYYYY 
 
 
ZZZZZ 
… 
… 
 
 
 
 
 
 
 
 
 
Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of 
the study drug. 
World Health Organization-Drug Dictionary (WHO-DD) Version xx, YYYY 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 108 of 126 
 
 
Programing Note: 
Same as Listing 16.2.10.2.1 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Listing 16.2.10.2.2 Concomitant Medication MAD (Safety Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 109 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.1.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Repeat for following days: Day 1, Day 7 
 
 
Figure 14.2.1.1.1 Individual Plasma Concentrations of CVN766 vs Time (Linear) SAD (Pharmacokinetic Population) 
Treatment: CVN766 5 mg 
 
 
 
Source Listing: 16.2.6.1.1 
Programming Note: 
The x-axis will represent the study time in hours (0 – 72 hours). 
The y-axis will represent the Plasma Concentrations (unit). The y-axis will be on the linear scale. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 
 
 
Figure 14.2.1.1.2 Individual Plasma Concentrations of CVN766 vs Time (Linear) MAD (Pharmacokinetic Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 110 of 126 
 
 
Programing Note: 
Same as Figure 14.2.1.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.1.1.3 Individual Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Linear) MAD (Pharmacokinetic Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 111 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.1.2.1 Individual Plasma Concentrations of CVN766 vs Time (Semi-Log) SAD (Pharmacokinetic Population) 
Treatment: CVN766 5 mg 
Source Listing: 16.2.6.1.1 
Programming Note: 
The x-axis will represent the study time in hours (0 – 72 hours). 
The y-axis will represent the Plasma Concentrations (unit). The y-axis will be on the semi-log scale. 
All participants per treatment group (one page for each treatment group) will be represented on a single page. Each subject will be presented as a distinct line type. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 112 of 126 
 
 
Programing Note: 
Same as Figure 14.2.1.2.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Repeat for: Day 1, Day 7 
 
Figure 14.2.1.2.2 Individual Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 113 of 126 
 
 
Programing Note: 
Same as Figure 14.2.1.2.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.1.2.3 Individual Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 114 of 126 
 
 
 
Figure 14.2.2.1.1 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Linear) SAD (Pharmacokinetic Population) 
Treatment: CVN766 5 mg 
 
 
Source Listing: 16.2.6.1.1 
Programming Note: 
The x-axis will represent the study time in hours (0 –72 hours). 
The y-axis will represent the mean (+/-SD) Plasma Concentrations (unit). The y-axis will be on the linear scale. 
Each dose level for the active treatment will be presented as a distinct line type. Placebo will be excluded. 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 115 of 126 
 
 
Programing Note: 
Same as Figure 14.2.2.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Repeat for: Day 1, Day 7 
 
Figure 14.2.2.1.2 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time (Linear) MAD (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 116 of 126 
 
 
Programing Note: 
Same as Figure 14.2.2.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.2.1.3 Mean (+/- SD) Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Linear) MAD (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 117 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 45 mg(Fed), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.2.2.1; 
Source Listing: 16.2.6.1.2; 
 
Figure 14.2.2.2.1 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time (Semi-Log) SAD (Pharmacokinetic Population) 
Treatment: CVN766 5 mg 
 
Source Listing: 16.2.6.1.1 
Programming Note: 
The x-axis will represent the study time in hours (0 –72 hours). 
The y-axis will represent the mean (+/-SD) Plasma Concentrations (unit). The y-axis will be on the logarithmic scale. 
All treatments will be represented on a single page. Each treatment group will be presented as a distinct line type. 
 
 
 
 
 
Figure 14.2.2.2.2 Mean (+/- SD) Plasma Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 118 of 126 
 
 
 
 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Repeat for: Day 1, Day 7 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 119 of 126 
 
 
Programing Note: 
Same as Figure 14.2.2.2.1; 
Source Listing: 16.2.6.1.2; 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.2.2.3 Mean (+/- SD) Plasma Ctrough Concentrations of CVN766 vs Time Post-Dose (Semi-Log) MAD (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 120 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.3.1.1 Plasma Cmax versus dose for CVN766 SAD (Log Scale)(Pharmacokinetic Population) 
Pharmacokinetic parameter: Cmax (unit) 
 
 
 
 
 
 
 
O 
 
 
100 
 
 
O 
 
 
 
O 
O 
 
 
 
O 
O 
Ln(Cmax) (unit) 
10 
 
O 
 
 
O 
O 
 
 
O 
 
 
 
1 
O 
 
 
O 
 
 
 
 
O 
 
 
 
 
0.1 
 
 
 
 
5 mg 
15 mg 
… 
250 mg 
 
ln(Dose) of CVN766 (unit) 
 
 
 
Source Listing: 16.2.6.1.1 
 
O Original values 
 
 = Power Model Curve 
 
Programming Note: 
The x-axis represents ln(dose) from 5 mg to 250 mg. 
The y-axis will represent the Cmax on a ln scale. 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 121 of 126 
 
 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
Figure 14.2.3.1.2 Plasma Cmax,ss versus dose for CVN766 MAD (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 122 of 126 
 
 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.3.2.1 Plasma AUCinf versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) 
 
 
 
Figure 14.2.3.3.1 Plasma AUC24 versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) 
 
 
 
Figure 14.2.3.3.2 Plasma AUC24 versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) 
 
 
 
Figure 14.2.3.4.1 Plasma AUCt versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) 
 
 
 
Figure 14.2.3.4.2 Plasma AUCt versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Figure 14.2.3.5.1 Plasma AUCtau versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 123 of 126 
 
 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg(Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
 
 
 
Figure 14.2.3.6.1 Plasma t1/2z versus dose for CVN766 SAD (Log Scale) (Pharmacokinetic Population) 
 
 
 
Figure 14.2.3.6.2 Plasma t1/2z versus dose for CVN766 MAD (Log Scale) (Pharmacokinetic Population) 
 
 
Programing Note: 
Same as Figure 14.2.3.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Figure 14.2.4.1.1 Dose-normalized Cmax versus dose for CVN766 SAD (Pharmacokinetic Population) 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 124 of 126 
 
 
Programing Note: 
 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 125 mg, CVN766 250 mg. 
 
Pharmacokinetic parameter: Cmax 
 
 
 
 
100 
 
 
80 
 
 
60 
 
 
40 
 
 
20 
 
 
0 
5 mg 
15 mg 
… 
250 mg 
Dose of CVN766 (unit) 
Source Listing: 16.2.6.1.1 
O Original values 
 
● 
 Geometric Means 
 
 
Programming Note: 
The x-axis represents dose from 5 to 250 mg. 
The y-axis will represent the dose normalized Cmax. 
 
O 
O 
O 
O 
O 
● 
O 
O 
● 
O 
● 
O 
O 
O 
O 
 
● 
 
O 
O 
O 
O 
O 
DN_Cmax 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Figure 14.2.4.1.2 Dose-normalized Cmax,ss versus dose for CVN766 MAD (Pharmacokinetic Population) 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 125 of 126 
 
 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.4.2.1 Dose-normalized AUCinf versus dose for CVN766 SAD (Pharmacokinetic Population) 
 
 
 
Figure 14.2.4.3.1 Dose-normalized AUC24 versus dose for CVN766 SAD (Pharmacokinetic Population) 
 
 
 
Figure 14.2.4.3.2 Dose-normalized AUC24 versus dose for CVN766 MAD (Pharmacokinetic Population) 
 
 
 
Figure 14.2.4.4.1 Dose-normalized AUCt versus dose for CVN766 SAD (Pharmacokinetic Population) 
 
 


Sponsor: Cerevance Gamma, Inc. 
Protocol: CVN766-101 
Data Cut-Off: 2022-10-26 
Figure 14.2.4.4.2 Dose-normalized AUCt versus dose for CVN766 MAD (Pharmacokinetic Population) 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Program: filepath_name, Output Name: filepath_name Creation Date/Time: YYYY-MM-DD HH:MM 
Page 126 of 126 
 
 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.1 
Add following treatment; 
CVN766 5 mg, CVN766 15 mg, CVN766 45 mg (Fasted), CVN766 125 mg, CVN766 250 mg. 
Programing Note: 
Same as Figure 14.2.4.1.1 
Source Listing: 16.2.6.1.2 
Add following treatment; 
CVN766 45 mg, CVN766 125 mg, CVN766 250 mg. 
 
Figure 14.2.4.5.1 Dose-normalized AUCtau versus dose for CVN766 MAD (Pharmacokinetic Population) 
 
 
 
Figure 14.2.4.6.1 Dose-normalized t1/2z versus dose for CVN766 SAD (Pharmacokinetic Population) 
 
 
 
 
 
Figure 14.2.4.6.2 Dose-normalized t1/2z versus dose for CVN766 MAD (Pharmacokinetic Population) 
 
 


 
Si g ni n g  r e a s o n: I a m  t h e A ut h or  
C er e v a n c e _ C V N 7 6 6 -1 0 1 _ S A P _ v 1. 0 _ 2 0 2 2 _ 1 0 _ 2 
0  
Fi n al  A u dit  R e p ort  
2 0 2 2 -1 0 -2 1  
 
 
 
 
 
" C er e v a n c e _ C V N 7 6 6-1 0 1 _ S A P _ v 1. 0 _ 2 0 2 2 _ 1 0 _ 2 0"  Hi st or y  
 D o c u m e nt cr e at e d b y 
 
2 0 2 2- 1 0- 2 0 - 1 0: 0 0: 0 5 P M  G M T  
 
 D o c u m e nt e m ail e d t o 
 f or si g n at ur e 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 1 7 P M  G M T  
 
 D o c u m e nt e m ail e d t o 
 f or si g n at ur e 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 1 7 P M  G M T  
 
 D o c u m e nt e m ail e d t o 
 f or si g n at ur e 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 1 7 P M  G M T  
 
 D o c u m e nt e m ail e d t o 
 f or si g n at ur e 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 1 7 P M  G M T  
 
 D o c u m e nt e m ail e d t o 
 f or si g n at ur e 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 1 8 P M  G M T  
 
 E m ail vi e w e d b y 
 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 2 4 P M  G M T  
 
 E m ail vi e w e d b y 
 
2 0 2 2- 1 0- 2 0 - 1 0: 0 1: 2 5 P M  G M T  
 
 
 v erifi e d i d e ntit y wit h A d o b e A cr o b at Si g n a ut h e nti c ati o n 
2 0 2 2- 1 0- 2 0 - 1 0: 0 3: 5 4 P M  G M T  
 
 
 h a s  a gr e e d  t o t h e t er m s of  u s e  a n d  t o d o  b u si n e s s 
el e ctr o ni c all y wit h N O V O T E C H ( A U S T R A LI A) P T Y L T D.  
2 0 2 2- 1 0- 2 0 - 1 0: 0 3: 5 4 P M  G M T  
 
 D o c u m e nt e -si g n e d b y 
 
 
Cr e at e d:  
B y: 
St at u s:  
2 0 2 2 -1 0 -2 0  
 
Si g n e d  
Tr a n s a cti o n  I D: 
C B J C H B C A A B A A u M U T z 7 Uf W 8 o 5 p o wj q s 9j Xi U K 9 b V 4 D K er  
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
Si g n at ur e D at e: 2 0 2 2- 1 0- 2 0 - 1 0: 0 3: 5 4 P M  G M T  - Ti m e  S o ur c e: s er v er  
 
 E m ail vi e w e d b y 
 
2 0 2 2- 1 0- 2 0 - 1 0: 2 9: 2 9 P M  G M T  
 
 
 v erifi e d i d e ntit y wit h A d o b e A cr o b at Si g n a ut h e nti c ati o n 
2 0 2 2- 1 0- 2 0 - 1 0: 3 9: 5 7 P M  G M T  
 
 
 h a s  a gr e e d  t o t h e t er m s of  u s e  a n d  t o d o  b u si n e s s 
el e ctr o ni c all y wit h N O V O T E C H ( A U S T R A LI A) P T Y L T D.  
2 0 2 2- 1 0- 2 0 - 1 0: 3 9: 5 7 P M  G M T  
 
 D o c u m e nt e -si g n e d b y 
 
Si g ni n g r e a s o n: I a p pr o v e  
Si g n at ur e D at e: 2 0 2 2- 1 0- 2 0 - 1 0: 3 9: 5 7 P M  G M T  - Ti m e  S o ur c e: s er v er  
 
 E m ail vi e w e d b y 
 
2 0 2 2- 1 0- 2 1 - 2: 0 8: 5 6 A M  G M T  
 
 
 v erifi e d i d e ntit y wit h A d o b e A cr o b at Si g n a ut h e nti c ati o n 
2 0 2 2- 1 0- 2 1 - 2: 1 0: 3 4 A M  G M T  
 
 
 h a s  a gr e e d  t o t h e t er m s of  u s e  a n d  t o d o  b u si n e s s  el e ctr o ni c all y 
wit h N O V O T E C H ( A U S T R A LI A) P T Y L T D.  
2 0 2 2- 1 0- 2 1 - 2: 1 0: 3 4 A M  G M T  
 
 D o c u m e nt e -si g n e d b y 
 
Si g ni n g r e a s o n: I h a v e r e vi e w e d 
Si g n at ur e D at e: 2 0 2 2- 1 0- 2 1 - 2: 1 0: 3 4 A M  G M T  - Ti m e  S o ur c e: s er v er  
 
 
 v erifi e d  i d e ntit y wit h  A d o b e  A cr o b at  Si g n 
a ut h e nti c ati o n  
2 0 2 2- 1 0- 2 1 - 3: 2 8: 5 4 A M  G M T  
 
 
 h a s  a gr e e d  t o t h e t er m s of  u s e  a n d  t o d o  b u si n e s s 
el e ctr o ni c all y wit h N O V O T E C H ( A U S T R A LI A) P T Y L T D.  
2 0 2 2- 1 0- 2 1 - 3: 2 8: 5 4 A M  G M T  
 
 D o c u m e nt e -si g n e d b y 
 
Si g ni n g r e a s o n: I h a v e r e vi e w e d 
Si g n at ur e D at e: 2 0 2 2- 1 0- 2 1 - 3: 2 8: 5 4 A M  G M T  - Ti m e  S o ur c e: s er v er  
 
 
 v erifi e d i d e ntit y wit h A d o b e A cr o b at Si g n a ut h e nti c ati o n 
2 0 2 2- 1 0- 2 1 - 8: 0 3: 2 8 A M  G M T  
 
 
 h a s  a gr e e d  t o t h e t er m s of  u s e  a n d  t o d o  b u si n e s s  el e ctr o ni c all y 
wit h N O V O T E C H ( A U S T R A LI A) P T Y L T D.  
2 0 2 2- 1 0- 2 1 - 8: 0 3: 2 8 A M  G M T  
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D


 
 D o c u m e nt e -si g n e d b y 
 
Si g ni n g r e a s o n: I h a v e r e vi e w e d 
Si g n at ur e D at e: 2 0 2 2- 1 0- 2 1 - 8: 0 3: 2 8 A M  G M T  - Ti m e  S o ur c e: s er v er  
 
 A gr e e m e nt c o m pl et e d.  
2 0 2 2- 1 0- 2 1 - 8: 0 3: 2 8 A M  G M T  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P P D