Clinical trial NCT04948827
Conditions: Smoking Cessation
Sponsor: Camino Pharma, LLC
Start date: 2021-07-20; Completion date: 2023-03-06
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a single center, first-in-human, randomized, double-blind, placebo-controlled, Single-Ascending Dose (SAD) / Multiple-Ascending Dose (MAD) study incorporating a food-effect cohort.

Detailed description:

Arms: arm 1: In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort. arm 2: In this two-period food-effect cohort, each healthy nonsmoker subject received the randomly assigned treatment (SBP-9330 or placebo) under fasting conditions (Period 1). After a 7- to 14-day washout period, subjects received the same single dose of SBP-9330 or placebo in a fed state (Period 2) 30 minutes after the start of an FDA High-Fat and High-Calorie Breakfast. A sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort. arm 3: In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort. arm 4: In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort. arm 5: In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort. arm 6: In Part A, cohorts of healthy nonsmokers were randomized to either active SBP-9330 or matching placebo. In each cohort a sentinel group of 2 subjects were randomized and dosed ahead of the rest of the cohort. A review of safety data was completed prior to administration of doses to the remainder of the cohort. arm 7: In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. arm 8: In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. arm 9: In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. arm 10: In Part B, cohorts of healthy nonsmokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. arm 11: In Part C, cohorts of healthy smokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. arm 12: In Part C, cohorts of healthy smokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts. arm 13: In Part C, cohorts of healthy smokers were randomized to receive once daily doses of active SBP-9330 or matching placebo for 14 consecutive days in increasing dose cohorts.
Interventions: intervention 1: SBP-9330 intervention 2: Placebo
Intervention descriptions: intervention 1: SBP-9330 oral capsules intervention 2: Placebo oral capsules

Protocol documents:
Prot_000.pdf: 
 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, FIRST-IN-HUMAN 
STUDY TO ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF 
SINGLE AND MULTIPLE ASCENDING DOSES OF SBP-9330 (WITH A NESTED 
FOOD-EFFECT ARM) AFTER ORAL ADMINISTRATION IN HEALTHY SUBJECTS 
Protocol Number: 
SBP-9330-101 
Altasciences Project Number: 
CNO-P5-319 
Investigational Product: 
SBP-9330 
Phase of Development: 
1 
Sponsor: 
Camino Pharma, LLC  
9920 Pacific Heights Blvd, Suite 150 San 
Diego, CA 92121 
USA 
Sponsor’s Contact Person:  
Gonul Velicelebi, PhD 
Chief Executive Officer 
COMPLIANCE 
The study will be conducted in accordance with standards of Good Clinical Practice, as defined by the 
International Council for Harmonisation and all applicable federal and local regulations. 
Protocol Version 
Date 
1.0 
FINAL 
April 22, 2021 
2.0 
AMENDMENT 1 
June 1, 2021 
3.0 
AMENDMENT 2 
December 10, 2021 
4.0 
AMENDMENT 3 
September 14, 2022 
 
CONFIDENTIALITY STATEMENT 
The information provided in this document is strictly confidential and is available for review to investigator(s) 
and to the appropriate Independent Ethics Committee (IEC) or Institutional Review Board (IRB). It may not be 
used, divulged, published or otherwise disclosed without the written authorization from Altasciences or the 
sponsor. 


Protocol No: SBP-9330-101 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ..................................................................................................................................... 6 
STUDY SYNOPSIS ..................................................................................................................................................... 7 
INVESTIGATOR AND STUDY ADMINISTRATIVE STRUCTURE ................................................................ 25 
1. INTRODUCTION .............................................................................................................................................. 26 
 Study Rationale ............................................................................................................................................. 26 
 Overview of Disease .............................................................................................................................. 26 
 Therapeutic Rationale ............................................................................................................................ 26 
 Background ................................................................................................................................................... 28 
 Mechanism of Action ............................................................................................................................. 28 
 Preclinical Experience ............................................................................................................................ 28 
 Clinical Experience ................................................................................................................................ 31 
 Rationale for Study Design and Dose Selection ............................................................................................ 31 
 Benefit/Risk Assessment ............................................................................................................................... 32 
2. STUDY OBJECTIVES AND ENDPOINTS .................................................................................................... 34 
3. STUDY DESIGN ................................................................................................................................................ 36 
 Adaptive Features and Risk Management of Study Design .......................................................................... 36 
 Data and Safety Monitoring Board (DSMB) ................................................................................................. 37 
 Overall Study Design .................................................................................................................................... 38 
 Part A – SAD Phase with Nested Food-Effect Cohort ........................................................................... 38 
 Part B - MAD Phase ............................................................................................................................... 41 
 Part C - Smoker Phase ............................................................................................................................ 43 
 Study Treatments ........................................................................................................................................... 44 
 Dose Escalation and Stopping Rules ............................................................................................................. 44 
 Individual Subject Stopping Rules ......................................................................................................... 44 
 Cohort Stopping Rules ........................................................................................................................... 45 
 Trial Stopping Rules .............................................................................................................................. 45 
4. SUBJECT POPULATION ................................................................................................................................ 47 
 Inclusion Criteria ........................................................................................................................................... 47 
 Exclusion Criteria .......................................................................................................................................... 48 
 Withdrawal Criteria ....................................................................................................................................... 50 
 Before First Treatment Administration .................................................................................................. 50 
 After First Treatment Administration..................................................................................................... 51 
 Lifestyle and/or Dietary Requirements ......................................................................................................... 51 
 Concomitant Treatment ................................................................................................................................. 52 


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5. STUDY TREATMENTS .................................................................................................................................... 53 
 Investigational Products ................................................................................................................................ 53 
 SBP-9330 ............................................................................................................................................... 53 
 Placebo ................................................................................................................................................... 53 
 Investigational Product Management ............................................................................................................ 53 
 Packaging, Labeling and Dispensing ..................................................................................................... 53 
 Storage and Handling ............................................................................................................................. 53 
 Method of Assigning Subjects to Treatment Groups ............................................................................. 53 
 Blinding .................................................................................................................................................. 54 
 Study Drug Accountability..................................................................................................................... 54 
 Administration of Study Drug ....................................................................................................................... 55 
 Part A – SAD phase with Nested Food-Effect Cohort ........................................................................... 55 
 Parts B and C – MAD and Smoker Phase .............................................................................................. 55 
 Treatment Compliance ........................................................................................................................... 55 
 Meals and Fluids ........................................................................................................................................... 55 
 Other Protocol Restrictions ........................................................................................................................... 56 
 Part A – SAD phase with Nested Food-Effect Cohort ........................................................................... 56 
 Parts B and C– MAD and Smoker Phase ............................................................................................... 56 
6. STUDY PROCEDURES .................................................................................................................................... 57 
 Safety Assessments ....................................................................................................................................... 57 
 Medical History ...................................................................................................................................... 57 
 Physical Examination ............................................................................................................................. 57 
 Vital Signs .............................................................................................................................................. 58 
 12-Lead Electrocardiogram .................................................................................................................... 59 
 Laboratory Evaluations .......................................................................................................................... 60 
 Columbia Suicide Severity Rating Scale (C-SSRS) ............................................................................... 60 
 Mini International Neuropsychiatric Interview (M.I.N.I.) ..................................................................... 61 
 Blood Volume Collected ............................................................................................................................... 61 
 Pharmacokinetic Assessments ....................................................................................................................... 61 
 Pharmacokinetic Sample Processing, Storage and Shipping .................................................................. 62 
 Residual Biological Samples .................................................................................................................. 62 
 Smoking Assessments for Part C only .......................................................................................................... 62 
 Fagerström Test for Cigarette Dependence (FTCD) .............................................................................. 62 
 Smoking Time-Line Follow-back (TLFB) ............................................................................................. 62 
 Expired Carbon Monoxide (ECO) Level ............................................................................................... 63 
 Blood Sampling for Cotinine ................................................................................................................. 63 
 Smoking Log .......................................................................................................................................... 63 


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 Minnesota Nicotine Withdrawal Scale (MNWS) ................................................................................... 63 
 Questionnaire on Smoking Urges – Brief version (QSU-Brief) ............................................................. 63 
7. ADVERSE EVENTS DOCUMENTATION .................................................................................................... 64 
 Definitions ..................................................................................................................................................... 64 
 Severity Assessment ...................................................................................................................................... 64 
 Causality Assessment .................................................................................................................................... 65 
 Adverse Event Monitoring ............................................................................................................................ 65 
 Reporting of Pregnancy ................................................................................................................................. 66 
 Serious Adverse Event Reporting ................................................................................................................. 67 
 Drug-Induced Liver Injury ..................................................................................................................... 67 
8. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ................................................................... 69 
 Analysis Populations ..................................................................................................................................... 69 
 Safety Population ................................................................................................................................... 69 
 Pharmacokinetic Population ................................................................................................................... 69 
 Demographic Data and Other Baseline Characteristics ................................................................................. 69 
 Safety............................................................................................................................................................. 69 
 Safety Endpoints .................................................................................................................................... 69 
 Safety Analysis....................................................................................................................................... 69 
 Safety Statistical Methodology .............................................................................................................. 69 
 Pharmacokinetics .......................................................................................................................................... 69 
 Missing Values ....................................................................................................................................... 69 
 Measurements Below the Lower Limit of Quantitation ......................................................................... 70 
 Actual Time ............................................................................................................................................ 70 
 Baseline Reference Timepoint ............................................................................................................... 70 
 Non-Compartmental Analysis ................................................................................................................ 70 
 Data Precision ........................................................................................................................................ 73 
 Pharmacokinetic Statistical Methodology .............................................................................................. 73 
 Smoking Assessment (Part C only) ............................................................................................................... 74 
 Planned Interim Pharmacokinetic Analyses .................................................................................................. 74 
 Determination of Sample Size ....................................................................................................................... 75 
9. REFERENCES ................................................................................................................................................... 76 
10. APPENDIX 1: ETHICS ..................................................................................................................................... 79 
 Institutional Review Board ............................................................................................................................ 79 
 Ethical Conduct of the Study ......................................................................................................................... 79 
 Subject Information and Consent .................................................................................................................. 79 
 Subject Confidentiality .................................................................................................................................. 79 
11. APPENDIX 2: DATA COLLECTION, RETENTION, AND MONITORING ............................................ 80 


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 Case Report Forms ........................................................................................................................................ 80 
 Data Management and Processing ................................................................................................................. 80 
 Quality Control and Quality Assurance......................................................................................................... 80 
 Record Retention ........................................................................................................................................... 80 
 Monitoring of the Study ................................................................................................................................ 81 
 Safety Oversight ............................................................................................................................................ 81 
12. APPENDIX 3: ADMINISTRATIVE PROCEDURES .................................................................................... 82 
 Liabilities ....................................................................................................................................................... 82 
 Adherence to Protocol ................................................................................................................................... 82 
 COVID-19 Response Plan ............................................................................................................................. 82 
 Statement of Investigator ............................................................................................................................... 82 
 Delegation of Investigator Duties .................................................................................................................. 82 
 Premature Termination or Suspension of a Study ......................................................................................... 83 
13. APPENDIX 4: PROTOCOL REVIEW AND APPROVALS ......................................................................... 84 
14. APPENDIX 5: LIST OF ABBREVIATIONS .................................................................................................. 87 
15. APPENDIX 6: CLINICAL LABORATORY EVALUATIONS ..................................................................... 90 
16. APPENDIX 7: COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) – 
BASELINE/SCREENING VERSION ..................................................................................................................... 91 
17. APPENDIX 8: COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) – SINCE LAST VISIT 
VERSION ................................................................................................................................................................... 92 
18. APPENDIX 9: MINI INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW (M.I.N.I) ................... 93 
19. APPENDIX 10: FAGERSTRÖM TEST FOR CIGARETTE DEPENDENCE (FTCD) ............................. 94 
20. APPENDIX 11: MINNESOTA NICOTINE WITHDRAWAL SCALE (MNWS) ....................................... 95 
21. APPENDIX 12: QUESTIONNAIRE ON SMOKING URGES – BRIEF VERSION (QSU-BRIEF) .......... 96 
22. APPENDIX 13: SUMMARY OF CHANGES AMENDMENT 1 ................................................................... 97 
23. APPENDIX 14: SUMMARY OF CHANGES AMENDMENT 2 ................................................................... 98 
24. APPENDIX 15: SUMMARY OF CHANGES AMENDMENT 3 ................................................................. 101 
 


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LIST OF IN-TEXT TABLES 
Table 1 
Schedule of Activities – Part A (SAD Phase with Nested Food-Effect Cohort) ....... 18 
Table 2 
Schedule of Activities – Part B (MAD Phase) .......................................................... 20 
Table 3 
Schedule of Activities – Part C (Smoker Phase) ....................................................... 22 
Table 4 
Toxicity Data of SBP-9330 in Non-GLP Studies ...................................................... 30 
Table 5 
Calculations of the Maximum Recommended Starting Dose of SBP-9330 in First 
in Human Clinical Trials in Adult Healthy Volunteers ............................................. 32 
Table 6 
Adaptive Features and Boundaries ............................................................................ 36 
Table 7 
Part A – SAD Phase with Nested Food-Effect Cohort Design and Dose Levels ...... 40 
Table 8 
Part B - MAD Phase Design and Dose Levels .......................................................... 42 
Table 9 
Part C - Smoker Phase Design and Dose Levels ....................................................... 43 
Table 10 
Vital Sign Recording Schedule – SAD Phase ........................................................... 58 
Table 11 
Vital Sign Recording Schedule – MAD and Smoker Phase ...................................... 59 
Table 12 
ECG Recording Schedule – SAD Phase .................................................................... 60 
Table 13 
ECG Recording Schedule – MAD and Smoker Phase .............................................. 60 
Table 14 
Adverse Event Relationship to Study Drug ............................................................... 65 
Table 15 
Pharmacokinetic Parameters of SBP-9330 in Plasma ............................................... 71 


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STUDY SYNOPSIS 
Name of 
Sponsor: 
Camino Pharma, LLC 
Name of 
Product: 
SBP-9330 
Title of Study: 
A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study to 
Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple 
Ascending Doses of SBP-9330 (with a Nested Food-Effect Arm) after Oral 
Administration in Healthy Subjects 
Study 
Development 
Phase: 
1 
Objectives: 
Primary Objective: 
• 
To assess the safety and tolerability of single and multiple ascending oral 
doses of SBP-9330 in healthy nonsmokers and healthy smokers 
Secondary Objectives: 
• 
To determine single and multiple oral dose pharmacokinetics (PK) of 
SBP-9330 in healthy nonsmokers and healthy smokers 
• 
To explore the effect of food on the single oral dose PK of SBP-9330 in 
healthy nonsmokers 
Exploratory Objectives: 
• 
 To explore the effect of SBP-9330 on smoking-related assessments 
Endpoints: 
Primary Endpoints – Safety and Tolerability: 
• 
Incidence and severity of adverse events (AEs) for subjects administered 
SBP-9330 compared to placebo 
• 
Changes in vital signs, physical examination findings, electrocardiogram 
(ECG) findings, Columbia-Suicide Severity Rating Scale (C-SSRS) 
questionnaire results, and clinical laboratory results for subjects 
administered SBP-9330 compared to placebo 
Secondary Endpoints - Pharmacokinetics: 
• 
Pharmacokinetic (PK) parameters, where appropriate, will be determined 
for SBP-9330 from individual concentration-time profiles in plasma.  
• 
Main PK parameters will be determined to assess the effect of food after 
a single oral dose of 600 mg SBP-9330. 
Exploratory Endpoints – Smoking Assessments: 
• 
Expired carbon monoxide (ECO) level  
• 
Plasma cotinine level 
• 
Number of cigarettes smoked (smoking log) 
• 
Minnesota Nicotine Withdrawal Scale (MNWS) responses 


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• 
Questionnaire on Smoking Urges – Brief version (QSU-Brief) responses 
Test Product, 
Dose, and Mode 
of 
Administration 
(proposed): 
SBP-9330 75-mg, 150-mg and 300-mg capsules 
Manufacturer: PACE Laboratory (previously Velesco Pharmaceutical Services, 
Inc.) 
Small batches of 75-mg dose strength capsules will also be prepared by the 
Altasciences pharmacy using a Sponsor-supplied procedure. 
Mode of administration: Oral 
Placebo, Dose, 
and Mode of 
Administration: 
Placebo (visually matching SBP-9330 75-mg, 150-mg and 300-mg capsules) 
Manufacturer: PACE Laboratory (previously Velesco Pharmaceutical Services, 
Inc.) 
Mode of administration: Oral 
Study Design: 
This is a single-center, first-in-human, randomized, double-blind, placebo-
controlled, SAD/MAD study incorporating a food-effect cohort. 
The study will include 3 parts: 
• 
Part A: SAD phase with a nested food-effect cohort 
• 
Part B: MAD phase 
• 
Part C: Smoker phase 
Part A - SAD Phase with Nested Food-Effect Cohort 
Healthy adult nonsmoker subjects will be randomized to receive a single oral dose 
of either SBP-9330 or placebo in each of 5 planned SAD cohorts. Each cohort 
will consist of 8 subjects in 3:1 (SBP-9330:placebo) ratio to have a total of 6 
subjects receiving SBP-9330 and 2 subjects receiving placebo. 
The proposed SAD design and planned escalation are as follows: 
Cohort 
N (active:placebo) 
Dose 
Drug administration 
A1 
6:2  
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
150 mg 
Single oral SBP-9330 or placebo 
administration 
A2 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
300 mg 
Single oral SBP-9330 or placebo 
administration 
A3 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects] 
for Period 1 only) 
600 mg 
Single oral SBP-9330 or placebo 
administration under fasted and fed 
conditions in 2-period food-effect cohort 
with 7- to 14-day washout 
A4 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
1200 mg 
Single oral SBP-9330 or placebo 
administration 
A5 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
2400 mg 
Single oral SBP-9330 or placebo 
administration 
 


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For Cohorts A1, A2, A4, and A5, each subject will receive the assigned treatment 
(SBP-9330 or placebo) under fasting conditions.  
For Cohort A3 (2-period food-effect cohort), each subject will receive the 
randomly assigned treatment (SBP-9330 or placebo) under fasting conditions in 
Period 1. After a 7- to 14-day washout period, subjects will receive the same 
single dose of SBP-9330 or placebo in a fed state in Period 2, 30 minutes after the 
start of an FDA High-Fat and High-Calorie Breakfast. Escalation to Cohort A4 
will be based only on the fasting period safety and PK and may proceed in 
parallel to the A3 fed period. 
All cohorts in the fasting state will be dosed according to a sentinel dosing design 
to ensure optimal safety. Initially, 2 subjects will be dosed; 1 subject will be 
dosed with SBP-9330 and 1 subject with placebo. If the safety and tolerability 
results of the first 24 hours following dosing for the initial subjects are acceptable 
to the Investigator, the other 6 subjects (5 active and 1 placebo) may be dosed 
approximately 24 hours after dosing of the sentinel group.  
Escalation to the next higher dose will only proceed if none of the stopping 
criteria have been reached and when the safety and tolerability and available 
plasma PK analysis of the previous dose, including delayed significant AEs in 
earlier cohorts, are acceptable to the Investigator, Sponsor and Data and Safety 
Monitoring Board (DSMB). 
The SAD Phase will have a maximum of 5 cohorts. The number of cohorts may 
be changed at the discretion of the Sponsor depending on the emerging safety and 
plasma PK data from the previous cohorts. The dose levels proposed for SAD 
cohorts may be adjusted during the course of the study based on preliminary 
safety and plasma PK data but escalation will not be more than 3-fold the 
previous dose. 
Part B - MAD Phase 
Healthy adult nonsmoker subjects will be randomized to receive either SBP-9330 
or placebo orally in each of the 3 planned MAD cohorts. Each cohort will consist 
of 10 subjects in 4:1 (SBP-9330:placebo) ratio to have a total of 8 subjects 
receiving SBP-9330 and 2 subjects receiving placebo. An additional MAD cohort 
(Cohort B4) may be added at the discretion of the Sponsor depending on 
emerging safety and plasma PK data from previous cohorts. 
The proposed MAD design and planned escalation are as follows: 
Cohort 
N 
(active:placebo) 
Dose  
Drug administrations 
B1 
8:2 
adaptive  
Once daily oral administrations for 14 
consecutive days  
B2 
8:2 
adaptive  
Once daily oral administrations for 14 
consecutive days  
B3 
8:2 
adaptive  
Once daily oral administrations for 14 
consecutive days  
Additional 
B4 
8:2 
adaptive 
Once daily oral administrations for 14 
consecutive days 
Each subject will receive once daily oral administration of the assigned treatment 
under fasting conditions (SBP-9330 or placebo) for 14 consecutive days.  


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The MAD phase of the study may commence in parallel to the SAD or thereafter. 
The decision on how early the MAD phase of the study may be started and the 
doses to be administered will be determined by the Sponsor after consultation 
with the DSMB based on emerging safety and PK data. The first MAD daily dose 
will be less than or equal to an already well-tolerated SAD dose for which 
complete safety and PK data are available.  
All relevant safety and plasma PK data will be reviewed by the DSMB before any 
dose escalation. The dose levels proposed for MAD cohorts may be adjusted 
during the course of the study based on preliminary safety and PK data. The 
dosing frequency may also be changed from once daily to twice daily, without 
changing the total daily dose outlined in the protocol.  
The MAD phase will have a maximum of 4 cohorts. The number of cohorts may 
be decreased at the discretion of the Sponsor depending on the emerging safety 
and PK data from the proceeding cohorts. The increase from one dose level to the 
next dose level will not be more than 3-fold. A MAD daily dose level cannot be 
higher than the highest dose level administered in the SAD phase. 
All subjects who complete the study and those terminating early will be required 
to complete the End of study/Follow-up procedures. 
Part C – Smoker Phase 
Healthy adult smokers will be randomized to receive either SBP-9330 or placebo 
orally in each of the 2 planned smoker cohorts. Each cohort will consist of 
10 subjects randomly assigned in a 4:1 (SBP-9330:placebo) ratio, for a total of 
8 subjects receiving SBP-9330 and 2 subjects receiving placebo. 
The proposed Smoker phase design and planned escalation are as follows: 
Cohort 
N (active:placebo) 
Dose  
Drug administrations 
C1 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
C2 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
Additional C3 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days 
Each subject will receive once daily oral administration of the assigned treatment 
(SBP-9330 or placebo) under fasting conditions for 14 consecutive days.  
The Smoker phase of the study may commence after completion of dosing in the 
MAD phase of the study. The Smoker cohort daily dose will be less than or equal 
to the highest MAD dose for which complete safety and PK data are available.  
All relevant safety and PK data will be reviewed by the DSMB before any dose 
escalation. The DSMB will be provided the randomization code to aide in the 
review. The dose levels proposed for Smoker cohorts may be adjusted during the 
course of the study based on preliminary safety and PK data. 
The Smoker phase will have a maximum of 3 cohorts. There are 2 planned 
cohorts and an additional cohort may be added depending on the emerging PK 


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and safety data in the previous cohorts. A Smoker cohort daily dose level cannot 
be higher than the highest dose level administered in the MAD phase.  
All subjects who complete the study and those terminating early will be required 
to complete the End of Study/Follow-up procedures. 
Study 
Population: 
Healthy adult male and female subjects aged 18 to 55 years, inclusive. 
Planned Number 
of Subjects: 
Part A – SAD Phase with nested Food-Effect Cohort: 40 subjects (5 cohorts of 8 
subjects each). 
Part B – MAD Phase: 30 subjects (3 cohorts of 10 subjects each). An additional 
MAD cohort (10 subjects) may be added in Part B, depending on the emerging 
PK and safety data in the previous cohorts. 
Part C – Smoker Phase: 20 subjects (2 cohorts of 10 subjects each). An additional 
Smoker cohort (10 subjects) may be added in Part C depending on the emerging 
PK and safety data in the previous cohorts. 
Subjects cannot be enrolled in more than 1 cohort or study part. 
Study Drug 
Administration: 
Part A - SAD Phase with Nested Food-Effect Cohort 
For Cohorts A1, A2, A4, and A5: The assigned dose of SBP-9330 or placebo will 
be administered orally with approximately 240 mL of water in the morning, 
following a minimum 10-hour overnight fast. An additional volume of water of 
up to 150 mL may be provided in 50 mL increments to ensure that the whole 
dose is administered. 
For Cohort A3 only: In Period 1, the assigned dose of SBP-9330 or placebo will 
be administered orally with approximately 240 mL of water in the morning, 
following a minimum 10-hour overnight fast. During Period 2, the assigned dose 
of SBP-9330 or placebo will be administered orally with approximately 240 mL 
of water in the morning, following a minimum 10-hour overnight fast and 30 
minutes after the start of a high-fat, high-calorie breakfast. An additional volume 
of water of up to 150 mL may be provided in 50 mL increments to ensure that the 
whole dose is administered. 
Parts B and C - MAD Phase and Smoker Phase 
The assigned dose of SBP-9330 or placebo will be administered orally with 
approximately 240 mL of water in the morning, once daily for 14 consecutive 
days, and each dose will follow a minimum 10-hour overnight fast. An additional 
volume of water of up to 150 mL may be provided in 50 mL increments to ensure 
that the whole dose is administered. 
Duration of 
Treatment and 
Subject 
Confinement: 
Part A - SAD Phase with Nested Food-Effect Cohort 
Duration of clinical trial (per subject): 
Screening: Day -28 to Day -1 (up to 28 days) 
Cohorts A1, A2, A4, and A5:  
• 
Subjects will be confined to the clinical research unit (CRU) from at least 
10 hours prior to drug administration until approximately 48 hours after 


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study drug administration. Subjects will therefore be confined for 4 days 
and 3 nights (Day -1 to Day 3). 
• 
Subjects will return for a follow-up visit approximately 5 days after the 
last PK blood sample/discharge (Day 8±1). 
• 
Total study duration: up to 38 days (including Screening) 
Cohort A3 (food-effect cohort):  
• 
In each period, subjects will be confined to the CRU from at least 
10.5 hours prior to drug administration until approximately 48 hours after 
study drug administration. Subjects will therefore be confined for 4 days 
and 3 nights (Day -1 to Day 3) in each period. 
• 
Washout period between treatment administrations: at least 7 to 14 
calendar days 
• 
Subjects will return for a follow-up visit approximately 5 days after the 
last PK blood sample/discharge (Day 8±1) of Period 2. 
• 
Total study duration: up to 52 days (including Screening) 
Parts B and C - MAD Phase and Smoker Phase 
Duration of clinical trial (per subject): 
Screening: Day -28 to Day -1 (up to 28 days) 
Subjects will be confined to the CRU from at least 10 hours prior to drug 
administration until approximately 48 hours after last study drug administration. 
Subjects will therefore be confined for 17 days and 16 nights (Day -1 to Day 16). 
Subjects will return for a follow-up visit approximately 5 days after the last PK 
blood sample/discharge (Day 21±1). 
The total study duration will be up to 50 days (including Screening). 
Safety Meetings 
for Dose 
Escalation and 
Adjustments: 
A DSMB will be established to assure that the safety of study subjects is 
protected while the scientific goals of the study are being met. Specifically, the 
DSMB is charged with monitoring the safety of participants and the quality of the 
data, as well as recommending the appropriate termination of study when risks 
have been uncovered or when it appears that the clinical trial cannot be concluded 
successfully. The DSMB is responsible for reviewing and evaluating safety and 
available plasma PK data collected after each cohort and making a 
recommendation for dose escalation and adjustments. 
The DSMB, at a minimum, will review safety data up to discharge and available 
plasma PK data of all the subjects in the respective cohort in a blinded manner to 
decide whether to escalate doses between cohorts. The DSMB will be provided 
the randomization code to aide in the review for Part C.  The minimum number 
of subjects required to decide on dose escalation is 6 subjects (i.e., at least 4 on 
active treatment) for Part A (SAD Phase) and 8 subjects (i.e., at least 6 on active 
treatment) for Parts B (MAD Phase) and C (Smoker Phase).  
The DSMB will also advise as to when MAD dosing may commence and 
whether any stopping criteria were met. These assessments will generally be 
made without breaking the randomization code. If judged necessary by the 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
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DSMB, an individual or the complete cohort may be unblinded during evaluation 
of the study data. Before unblinding, a decision should be made about the action 
to be taken based on the revealed treatment allocation. The DSMB may advise 
adjusting the dose based on the treatment-emergent safety and available PK data.  
Inclusion 
Criteria 
1. Provision of written informed consent prior to the initiation of any protocol-
specific procedures 
2. Stated willingness to comply with all study procedures and availability for 
the duration of the study 
3. Healthy male or female subject ≥ 18 and ≤ 55 years of age 
4. Body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 32.0 kg/m2  
5. Body weight ≥ 50.0 kg at Screening 
6. A female subject must meet at least one of the following criteria: 
a. Is of childbearing potential and agrees to use an acceptable contraceptive 
method. Acceptable contraceptive methods include: 
• 
Total abstinence, in accordance with the lifestyle of the subject, from 
at least 30 days prior to the first study drug administration through to 
at least 90 days after the last dose of the study drug 
• 
One of the following contraceptive methods, used in combination 
with a barrier method (e.g., a diaphragm, a cervical cap, or a 
condom), from at least 30 days prior to the first study drug 
administration through to at least 90 days after the last dose of the 
study drug: 
▪ 
Intrauterine device (with or without hormones) 
▪ 
Spermicide 
Or 
b. Is of non-childbearing potential, defined as surgically sterile (i.e., has 
undergone complete hysterectomy, bilateral oophorectomy, or tubal 
ligation) or is in a postmenopausal state (i.e., at least 1 year without 
menses prior to the first study drug administration without an alternative 
medical condition and confirmed with a serum follicle-stimulating 
hormone [FSH] > 40 IU/L at Screening) 
7. Male subjects, if not surgically sterilized, must agree to use adequate 
contraception and not donate sperm from the first admission to the CRU until 
90 days after the last study drug administration. Adequate contraception for 
the male subject (and/or his female partner) includes the following: 
• 
Use of spermicide, hormonal contraceptives or an intrauterine device 
combined with at least one of the following forms of contraception: a 
diaphragm, a cervical cap, or a condom 
• 
Double-barrier method 
Total abstinence, in accordance with the lifestyle of the subject, from at least 
30 days prior to the first study drug administration until 90 days after the last 
study drug administration, is also acceptable 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
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8. Parts A and B only: Never or non smoker (a non smoker is defined as 
someone who completely stopped using nicotine products for at least 2 years 
prior to the first study drug administration 
9. Have no clinically significant medical or mental health conditions captured in 
the medical history or evidence of clinically significant findings on the 
physical examination and/or ECG, as determined by an Investigator 
10. No clinically significant abnormalities in blood pressure, heart rate, body 
temperature and respiratory rate and no evidence of orthostatic hypotension 
or postural tachycardia at Screening as defined below: 
a) 100 mmHg ≤ systolic blood pressure (BP) ≤ 140 mmHg in supine 
position. 
b) 60 mmHg ≤ diastolic BP ≤ 90 mmHg in supine position. 
c) 60 beats per minute (bpm) ≤ heart rate ≤ 100 bpm in supine position. 
d) 35.5 °C ≤ body temperature ≤ 37.5 °C. 
e) 10 breaths per minute ≤ respiratory rate ≤ 22 breaths per minute. 
f) ≥ 20 mmHg decrease in systolic BP from supine to standing. 
g) ≥ 10 mmHg decrease in diastolic BP from supine to standing. 
h) ≥ 30 bpm increase in heart rate from supine to standing. 
Part C Only: 
11. Are current tobacco cigarette smokers who smoke an average of 10 or more 
cigarettes per day in the 30 days prior to Screening  
12. Expired breath CO level ≥10 parts per million (ppm) at Screening and prior 
to the first study drug administration 
13. Positive test result for cotinine at Screening and prior to the first study drug 
administration 
14. Are not motivated to try to quit smoking from Screening through 30 days 
from the first study drug administration 
Exclusion 
Criteria: 
1. Female who is lactating 
2. Female who is pregnant according to the pregnancy test at Screening or prior 
to the first study drug administration 
3. Female who is planning to become pregnant during this study or within 90 
days after the last study drug administration 
4. Male with female partner who is pregnant, lactating, or planning to become 
pregnant during this study or within 90 days after the last study drug 
administration 
5. Poor venous access as determined by an Investigator at Screening 
6. History of significant hypersensitivity to SBP-9330 or any related products 
(including excipients of the formulations) as well as severe hypersensitivity 
reactions (like angioedema) to any drugs 
7. Presence of any medical condition that, in the opinion of an Investigator, 
poses an unacceptable risk to the subjects 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
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8. Presence or history of significant gastrointestinal, liver or kidney disease, or 
surgery that may affect drug absorption 
9. Evidence or history of clinically significant cardiovascular, pulmonary, 
hematologic, psychiatric (including mood and substance use disorders), 
neurological (including migraines, seizures, and epilepsy), endocrine, renal, 
hepatic, gastrointestinal, immunologic or dermatologic disease 
10. History of malignancy within the past five years, except for successfully 
treated basal cell carcinoma of the skin 
11. History of suicidal ideation or suicidal behavior as per the C-SSRS  
questionnaire administered at Screening 
12. Evidence or history of significant psychiatric disease or any DSM-5 disorder 
as assessed by the Mini International Neuropsychiatric Interview (M.I.N.I.) 
administered at Screening 
13. Routine or chronic use of more than three grams of acetaminophen daily 
14. Strenuous activity, sunbathing, and contact sports within 48 hours prior to 
(first) admission to the CRU  
15. Current alcohol consumption exceeding two standard drinks per day on 
average (1 standard drink=10 grams of alcohol) for male subjects and one 
standard drink per day on average for female subjects 
16. History of alcohol or drug (other than caffeine) use disorder within 
12 months prior to Screening  
17. Any clinically significant illness in the 28 days prior to the first study drug 
administration 
18. QTcF interval (QT interval corrected for heart rate according to Fridericia) > 
450 ms for males and > 470 ms for females at Screening or on Day –1 
19. Parts A and B only: Positive test result for alcohol and/or drugs of abuse at 
Screening or prior to the first drug administration 
20. Positive test results for HIV-1/HIV-2 antibodies, hepatitis B surface antigen 
or hepatitis C antibody  
21. Consumption of any prescription drugs (with the exception of hormonal 
contraceptives or hormone replacement therapy) or over-the-counter 
medications and nutrients known to modulate cytochrome P450 (CYP450) 
enzymes activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, 
or Seville [blood] orange products) or St. John’s Wort within 14 days prior to 
the first study drug administration 
22. Consumption of other prescription and over-the-counter medication not 
specifically excluded by Exclusion Criterion 21 including health supplements 
and herbal remedies within 7 days prior to the first study drug administration 
(an exception is made for paracetamol [acetaminophen], which is allowed up 
to admission to the clinic). 
23. Any other clinically significant abnormalities in laboratory test results at 
Screening that would, in the opinion of an Investigator, increase the subject's 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
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risk of participation, jeopardize complete participation in the study, or 
compromise interpretation of study data 
24. Intake of an investigational product in the 30 days or 5 half-lives (whichever 
is longer) prior to Screening 
25. Inclusion in a previous cohort of this clinical study 
26. Employee of the contract research organization (CRO) or the Sponsor. 
27.  Blood donation (excluding plasma donation) of approximately 500 mL 
within 56 days prior to Screening 
28. Plasma donation within 7 days prior to Screening 
Part C Only: 
29. History of generalized rash reaction to any drugs 
30. Positive test result (except cotinine) for alcohol and/or drugs of abuse at 
Screening or prior to the first study drug administration 
31. Use of smoking cessation aids (NRT, bupropion, or varenicline) within 
30 days prior to the first study drug administration 
32. Unable to abstain from smoking tobacco cigarettes for at least 1 hour before 
and 2 hours after study drug administration 
33. Unable to abstain from using nicotine-containing products other than tobacco 
cigarettes (e.g., pipes, cigars, e-cigarettes or vapes, nicotine topical patches, 
nicotine gum, or nicotine lozenges) during the study 
Bioanalysis: 
SBP-9330 plasma concentrations will be measured by a validated bioanalytical 
method. 
Part C only: Cotinine plasma concentrations will also be measured by a validated 
bioanalytical method. 
Safety Analysis 
Safety data including adverse events, changes in vital signs, physical examination 
findings, ECG findings, C-SSRS) questionnaire results, and clinical laboratory 
results will be summarized by treatment and dose level.  
Pharmacokinetic 
Analysis: 
Plasma samples for determination of SBP-9330 concentration will be collected at 
various time points throughout the study.  
PK analyses will be performed by non-compartmental analysis, and will be 
further detailed in the SAP. The following PK parameters in plasma will be 
calculated for SBP-9330 in each study part: 
Part A: SAD Phase with nested Food-Effect cohort  
Day 1: Cmax, Tmax, AUC0-24, AUC0-T, AUC0-∞, Thalf, CL/F, and Vz/F  
Day 8 (Cohort A3, Food-Effect only): Cmax, Tmax, AUC024, AUC0-T, AUC0-∞, Thalf, 
CL/F, and Vz/F  
Parts B and C: MAD Phase and Smoker Phase 
Day 1: Cmax, Tmax, AUC0-24, AUC0-T 
Days 7, 11, 12, and 13: Ctrough 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
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Day 14: Ctrough, Cmax, Tmax, Cτ, AUCτ, AUC0-T, effective Thalf, Thalf, CL/Fss, Vz/Fss, 
RAC(Cmax), RAC(AUC) 
Smoking 
Assessments 
(Part C only): 
Expired CO values, cotinine levels, number of cigarettes smoked, MNWS 
responses, and QSU-Brief responses will be summarized by treatment and dose 
level. 
Statistical 
Analysis: 
Descriptive statistics will be calculated for plasma SBP-9330 concentrations at 
each individual time point (or time interval, for urine) and for all PK parameters; 
individual and mean concentration-time profiles will also be presented.  
For all study phases, the appropriate PK parameters (Cmax, AUCs) will be 
assessed statistically for dose proportionality. Proportionality analysis will be 
done using a power model. Dose proportionality may be assessed within different 
dose ranges, if deemed appropriate, with at least three doses. 
For SAD Phase Cohort A3, a statistical comparison will be performed to evaluate 
the effect of food on the PK of SBP-9330 with the natural logarithmic 
transformation of Cmax, AUC0-t, and AUC0-∞. The 90% confidence interval for the 
exponential of the difference in least-squares (LS) means between the Fed and 
Fasting conditions will be calculated (Fed to Fasting ratio of geometric LS 
means). The parameter Tmax will be evaluated descriptively. 
For the MAD and Smoker cohorts, Ctrough will be displayed graphically and 
summarized descriptively to assess for steady state.  
Smoking data will be summarized by treatment and dose level using descriptive 
statistics. 
The statistical analysis of safety, PK, and smoking data will be further detailed in 
the SAP. 
 
 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 18 of 104 
Table 1 Schedule of Activities – Part A (SAD Phase with Nested Food-Effect Cohort) 
 
Assessment Period1  
 
Visit2 
Screening 
Pretreatment 
Treatment 
Follow-up/ End of 
Study3 
Study Day 
-28 to -2 
-1 
1 
(Predose) 
1 
2 
3 
8±1 
Confinement 
 
X 
X 
X 
X 
X 
 
Ambulatory 
X 
 
 
 
 
 
X 
Admission 
 
X 
 
 
 
 
 
Discharge 
 
 
 
 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
Eligibility Check 
X 
X 
X 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Physical Examination 
X 
X4 
 
 
 
X4 
X 
Body Weight and Height (Including BMI 
Calculation) 
X 
X5 
 
 
 
 
 
Serology (HBsAg, HCVAb, anti-HIV 
1 and 2) 
X 
 
 
 
 
 
 
Urine Drug and Alcohol Screen6 
X 
X 
 
 
 
 
 
FSH (postmenopausal females only) 
X 
 
 
 
 
 
 
Pregnancy Test (Females Only)7 
X 
X 
 
 
 
 
X 
Clinical Laboratory Tests6,8 
X 
X 
X 
 
 
X 
X 
12-lead ECG9,10 
X 
X 
X 
X 
 
X 
X 
Vital Signs10,11 
X 
X 
X 
X 
X 
X 
X 
C-SSRS Questionnaire12 
X 
X 
 
 
 
X 
X 
M.I.N.I. 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
Study Drug Administration 
 
 
 
X 
 
 
 
Blood Sampling for PK10,13 
 
 
X 
X 
X 
X 
 
Previous and Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 19 of 104 
 
Assessment Period1  
 
Visit2 
Screening 
Pretreatment 
Treatment 
Follow-up/ End of 
Study3 
Study Day 
-28 to -2 
-1 
1 
(Predose) 
1 
2 
3 
8±1 
Adverse Event Monitoring 
 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; 
FSH = follicle-stimulating hormone; HBsAg = hepatitis B surface antigen; HCVAb=hepatitis C virus antibody; HIV = human immunodeficiency 
virus; M.I.N.I. = Mini International Neuropsychiatric Interview; P K= pharmacokinetic; SAD = single ascending dose;  
1 
Subjects will be in the clinic from Day -1 until 48 hours (Day 3) post-dose. Subjects will return for follow-up/EOS assessments on Day 8±1. 
Subjects for the fed period of the food-effect cohort (Cohort A3) should report to the clinic after the washout period (at least 7 to 14 days 
after fasting dose) and repeat the 8-day SAD schedule of assessments beginning on Day -1. 
2 
The timing, type, and number of safety and PK assessments may be updated depending on emerging safety and PK data. 
3 
Subjects who discontinue the study early should complete the EOS procedures. Subjects in SAD cohorts A1, A2, A4, and A5 should return 
to the clinic for follow-up at Day 8±1; subjects in the food-effect 2-period cohort (Cohort A3) should return to the clinic for follow-up at Day 
8±1 in Period 2 (5 days after the last PK blood sample in fed part). 
4 
An abbreviated physical examination may be performed at the Investigator’s discretion upon admission and discharge from the clinical site. 
5 
Weight only. 
6 
See APPENDIX 6 for details. 
7 
Serum pregnancy test for all female subjects at Screening and urine pregnancy test, for female subjects of childbearing potential only, at all 
other timepoints. 
8 
Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): at Screening; on Day -1 
(admission) and at pre-dose, 48 hours post-dose; and at follow-up/EOS. 
9 
Triplicate 12-lead ECG: at Screening; Day -1 (admission), at pre-dose (within 60 minutes of dosing) and at 1, 3, 6, and 12 hours post-dose 
(±15 minutes); prior to discharge, and at follow-up/EOS. 
10 
When safety and PK blood draws coincide, procedures should be carried out in the following order: (1) ECGs, (2) vital signs, (3) PK blood 
sampling (nominal). 
11 
Vital signs: Screening; Day -1 (admission); at pre-dose (within 60 minutes of dosing) and at 0.75, 1.25, 1.75, 3.75, 8, 11.75, and 23.25 hours 
post-dose (±15 minutes); prior to discharge; and at follow-up/EOS. Orthostatic measurements will be obtained at Screening, Day -1, pre-
dose, and at 1.75 hours (±15 minutes) post dose.  For orthostatic measurements blood pressure and pulse rate will be measured after the 
subject has been in the supine position for at least 5 minutes, repeat measurements will be taken after the subject has been standing in the 
upright position for at least 2 to 3 minutes (respiratory rate and temperature will be measured with blood pressure and pulse rate in the supine 
position only). 
12 
A baseline/screening version of the C-SSRS will be used at Screening and a “since-last-visit” version will be used at all subsequent visits 
where the C-SSRS is administered. 
13 
Blood sampling for PK of SBP-9330 in plasma: at pre-dose (within 60 minutes of dosing) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 
48 hours post-dose (±10%). 
 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 20 of 104 
Table 2 Schedule of Activities – Part B (MAD Phase) 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Follow-up/ 
End of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 
21±1 
Confinement 
 
X 
X 
X X X X X X X X X X X X X X X 
X 
 
Ambulatory2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
X 
Body Weight and Height 
(Including BMI Calculation) 
X 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (HBsAg, HCVAb, 
anti-HIV 1 and 2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug and Alcohol Screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test (Females Only)6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical Laboratory Test5,7 
X 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
12-lead ECG8,9 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Vital Signs9,10 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Eligibility Check 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
 
 
X X X X X X X X X X X X X X 
 
 
 
Blood Sampling for PK9,11 
 
 
X 
X X 
 
 
 
 
X 
 
 
 
X X X X X 
X 
 
C-SSRS Questionnaire12 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
M.I.N.I. 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and Concomitant 
Medication 
X 
X 
X 
X X X X X X X X X X X X X X X 
X 
X 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 21 of 104 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Follow-up/ 
End of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 
21±1 
Adverse Event Monitoring 
 
X 
X 
X X X X X X X X X X X X X X X 
X 
X 
Abbreviations: BMI = body mass index; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; FSH = follicle-
stimulating hormone; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibody; HIV = human immunodeficiency virus; MAD = multiple 
ascending dose; M.I.N.I. = Mini International Neuropsychiatric Interview; PK = pharmacokinetic 
1 
The timing, type, and number of safety, and PK assessments may be updated depending on emerging safety and PK data. 
2 
Subjects who discontinue the study early should complete the EOS procedures. 
3 
An abbreviated physical examination may be performed at the Investigator’s discretion upon admission or discharge from the clinical site. 
4 
Weight only. 
5 
See APPENDIX 6 for details. 
6 
Serum pregnancy test for all female subjects at Screening and urine pregnancy test, for female subjects of childbearing potential only, at all other 
timepoints. 
7 
Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): at Screening; on Day -1 (admission); at 
pre-dose on Days 1, 3, 7, 14, and 16; and at follow-up/EOS. 
8 
Triplicate 12-lead ECG: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) on Day 1 and at 3 hours post-dose on each dosing day (i.e., 
Days 1 to 14) (±15 minutes); prior to discharge; and at follow-up/EOS. 
9 
When safety and PK blood draws coincide, procedures should be carried out in the following order: (1) ECGs, (2) vital signs, (3) PK blood sampling 
(nominal). 
10 
Vital signs: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) and 1.75 hours post-dose on each dosing day (i.e., Days 1 to 14) (±15 
minutes); prior to discharge; and at follow-up/EOS. Orthostatic measurements will be obtained at Screening, Day -1, pre-dose, and at 1.75 hours 
(±15 minutes) post dose.  For orthostatic measurements blood pressure and pulse rate will be measured after the subject has been in the supine position 
for at least 5 minutes, repeat measurements will be taken after the subject has been standing in the upright position for at least 2 to 3 minutes 
(respiratory rate and temperature will be measured with blood pressure and pulse rate in the supine position only). 
11 
Blood sampling for PK of SBP-9330 in plasma: at pre-dose (within 60 minutes of dosing); at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose 
(±10%) on Day 1; within 60 minutes prior to morning drug administration on Day 7, 11, 12, and 13; and within 60 minutes prior to drug administration 
and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 48 hours post-dose on Day 14 (±10%). 
12 
A baseline/screening version of the C-SSRS will be used at Screening and a “since-last-visit” version will be used at all subsequent visits where the 
C-SSRS is administered. 
 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 22 of 104 
Table 3 Schedule of Activities – Part C (Smoker Phase) 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Followup/ End 
of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 
21±1 
Confinement 
 
X 
X 
X X X X X X X X X X X X X X X 
X 
 
Ambulatory2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Smoking History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
X 
Body Weight and Height 
(Including BMI Calculation) 
X 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (HBsAg, HCVAb, 
antiHIV 1 and 2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug and Alcohol Screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test (Females Only)6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical Laboratory Test5,7 
X 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
12-lead ECG8,9 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Vital Signs9,10 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Eligibility Check 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
 
 
X X X X X X X X X X X X X X 
 
 
 
Blood Sampling for PK9,11 
 
 
X 
X X 
 
 
 
 
X 
 
 
 
X X X X X 
X 
 
Expired CO Level12 
X 
X 
X 
X X X X X X X X X X X X X X 
 
 
 
Blood Sampling for Cotinine13 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
Smoking Log 
 
X 
 
X X X X X X X X X X X X X X X 
 
 
FTCD 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 23 of 104 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Followup/ End 
of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 
21±1 
Smoking TLFB 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MNWS 
 
X 
 
X X X X X X X X X X X X X X 
 
 
 
QSU-Brief 
 
X 
 
X X X X X X X X X X X X X X 
 
 
 
C-SSRS Questionnaire14 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
M.I.N.I. 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and Concomitant 
Medication 
X 
X 
X 
X X X X X X X X X X X X X X X 
X 
X 
Adverse Event Monitoring 
 
X 
X 
X X X X X X X X X X X X X X X 
X 
X 
 
Abbreviations: BMI = body mass index; C-SSRS = Columbia-Suicide Severity Rating Scale; CO = carbon monoxide; ECG = electrocardiogram; EOS = end 
of study; FSH = follicle-stimulating hormone; FTCD = Fagerström Test for Cigarette Dependence; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis 
C virus antibody; HIV = human immunodeficiency virus; MAD = multiple ascending dose; M.I.N.I. = Mini International Neuropsychiatric Interview; MNWS 
= Modified Minnesota Nicotine Withdrawal Scale; PK = pharmacokinetic; QSU-Brief = Questionnaire on Smoking Urges – Brief version; TLFB = Smoking 
Time-Line Follow-back 
1 
The timing, type, and number of safety, and PK assessments may be updated depending on emerging safety and PK data. 
2 
Subjects who discontinue the study early should complete the EOS procedures. 
3 
An abbreviated physical examination may be performed at the Investigator’s discretion upon admission or discharge from the clinical site. 
4 
Weight only. 
5 
See APPENDIX 6 for details. 
6 
Serum pregnancy test for all female subjects at Screening and urine pregnancy test, for female subjects of childbearing potential only, at all other 
timepoints. 
7 
Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): at Screening; on Day -1 (admission); at 
pre-dose on Days 1, 3, 7, 14, and 16; and at follow-up/EOS. 
8 
Triplicate 12-lead ECG: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) on Day 1 and at 3 hours post-dose on each dosing day (i.e., 
Days 1 to 14) (±15 minutes); prior to discharge; and at follow-up/EOS. 
9 
When safety and PK blood draws coincide, procedures should be carried out in the following order: (1) ECGs, (2) vital signs, (3) PK blood sampling 
(nominal), (4) smoking assessments. 
10 
Vital signs: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) and 1.75 hours post-dose on each dosing day (i.e., Days 1 to 14) 
(±15 minutes); prior to discharge; and at follow-up/EOS. Orthostatic measurements will be obtained at Screening, Day -1, pre-dose, 1.75 hours 
(±15 minutes), and 3.5 hours (±15 minutes) post dose.  For orthostatic measurements blood pressure and pulse rate will be measured after the subject 
has been in the supine position for at least 5 minutes, repeat measurements will be taken after the subject has been standing in the upright position for 
at least 2 to 3 minutes (respiratory rate and temperature will be measured with blood pressure and pulse rate in the supine position only). 


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11 
Blood sampling for PK of SBP-9330 in plasma: at pre-dose (within 60 minutes of dosing); at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose 
(±10%) on Day 1; within 60 minutes prior to morning drug administration on Day 7, 11, 12, and 13; and within 60 minutes prior to drug administration 
and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 48 hours post-dose on Day 14 (±10%). 
12 
Expired breath CO will be measured with a Bedfont Smokerlyzer™.  
13 
Cotinine samples should be collected within 60-minutes prior to dosing on dosing days. 
14 
A baseline/screening version of the C-SSRS will be used at Screening and a “since-last-visit” version will be used at all subsequent visits where the 
C-SSRS is administered. 
 


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INVESTIGATOR AND STUDY ADMINISTRATIVE STRUCTURE 
SPONSOR’S CONTACT: 
 
Gonul Velicelebi, Ph.D., Chief Executive Officer 
Camino Pharma, LLC  
9920 Pacific Heights Blvd., Suite 150 
San Diego, CA 92121 
USA 
Phone: 
858-353-9440 
E-mail: gonul@caminopharma.com 
 
Joseph Djan, MBA – Clinical Operations Consultant 
Phone: 
858-381-7058 
E-mail: jdjan@exl-clinical.com  
PRINCIPAL INVESTIGATOR: 
Martin Kankam MD, PhD, MPH 
Altasciences Clinical Kansas, Inc. 
10103 Metcalf Avenue  
Overland Park, Kansas, 66212 
CLINICAL RESEARCH UNIT & SCREENING FACILITY: 
Altasciences Clinical Kansas, Inc. 
10103 Metcalf Avenue  
Overland Park, Kansas, 66212 
and/or 
10203 Metcalf Avenue  
Overland Park, Kansas, 66212 
and/or 
10183 Metcalf Avenue  
Overland Park, Kansas, 66212 
BIOANALYTICAL FACILITY: 
Altasciences 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
SCIENTIFIC AFFAIRS: 
 
Altasciences 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 
STATISTICAL FACILITY: 
Altasciences 
1200 Beaumont Ave. 
Mount-Royal, Quebec, Canada 
H3P 3P1 
DATA MANAGEMENT FACILITY: Altasciences 
10103 Metcalf Ave. 
Overland Park, KS 66212, United States 
PROJECT MANAGEMENT: 
 
Altasciences 
575 Armand-Frappier Blvd. 
Laval, Quebec, Canada 
H7V 4B3 


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1. 
INTRODUCTION 
SBP-9330 is a potent and selective mGlu2 positive allosteric modulator (PAM) with excellent 
drug-like properties including oral bioavailability and metabolic stability. Importantly, SBP-9330 
reduces nicotine self-administration and cue-induced nicotine reinstatement in rats without 
affecting natural food reward. In addition, SBP-9330 was well-tolerated and safe in pivotal (good 
laboratory practice [GLP]) 14-day toxicology studies in rats and dogs.  
 
Study Rationale 
 Overview of Disease 
Cigarette smoking remains the leading preventable cause of morbidity and mortality in the 
United States with the death toll from smoking and second-hand smoke exposure estimated at 
480,000 adults per year1. While smoking rates have been declining in adults without mental 
health conditions for decades, several new combustible, noncombustible, and electronic products 
have emerged, leading to a growing cohort of dually- and newly-addicted nicotine users. 
Although there are approximately 47 million tobacco users in the US1 and one billion worldwide, 
only three categories of medications – nicotine replacement therapies, the atypical antidepressant 
bupropion, and the nicotinic acetylcholine receptor partial agonist varenicline, have been 
approved by the U.S. Food and Drug Administration (FDA) to combat this pandemic. The 
long-term success rates of these FDA approved products are low, with 7-day point prevalence 
abstinence rates at 6 months of less than 25%2,3. Thus, there is considerable need for more 
effective therapeutics with different mechanisms of action which may be used as a single agent 
or in combination with other treatments. 
 Therapeutic Rationale 
Substance use disorder is a chronic condition marked by relapse to drug use even after prolonged 
abstinence, escalation of drug intake, tolerance to drug effects, craving, and continued use 
despite adverse consequences to health, financial status, and relationships4,5. Cigarette smoking, 
attributable primarily to the addictive properties of nicotine6,7, is one of the largest preventable 
causes of disease and death in the USA. According to the Centers for Disease Control and 
Prevention, cigarette smoking results in >400,000 premature deaths in the US each year, ~1 in 
every 5 deaths1. Additionally, e-cigarettes (e-cigs) have emerged as another highly effective 
nicotine delivery vehicle and represent the primary reason for increased nicotine addiction 
among young people. Cigarette smoking accounts for ~30% of all cancers, including 90% of 
lung cancer cases. While e-cigs do not exact the heavy carcinogenic toll that cigarettes do, they 
can actually be as addictive due to the greatly increased nicotine content of the vaping pods.  
There is a great incentive to quit smoking as it markedly reduces the risk of developing smoking-
related diseases and early death. Smokers can and do stop smoking – today in the US, there are 
more former smokers than current smokers. However, smoking cessation is very difficult and 
often takes multiple attempts. In the US, nearly 50-70% of adult smokers and approximately 
45% of high school-age smokers report that they tried to quit smoking in the past 12 months. In 
addition to behavioral therapies, there are FDA-approved medications to help those trying to quit 
smoking. Specifically, these include the atypical antidepressant bupropion (Zyban), the nicotinic 
acetylcholine receptor partial agonist varenicline (Chantix®), and nicotine replacement therapies 
(NRTs: nicotine patch, gum, lozenge, inhaler and nasal spray). The abstinence rates of these 


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FDA-approved products remain low, less than 25% overall2,3. Thus, there is a considerable need 
for more effective therapeutics with novel mechanisms of action.  
Extensive data suggest that glutamate, the primary excitatory neurotransmitter in the brain, 
critically modulates the actions of drugs of abuse8,9. For example, increases in excitatory 
glutamatergic transmission are likely to contribute to the positive reinforcing properties of 
addictive drugs10. Systemic psychostimulant administration, including nicotine11 and cocaine, 
increases glutamate levels in the ventral tegmental area and nucleus accumbens (NAc). These 
structures reside in the extended amygdala, a brain circuit that mediates the rewarding effects of 
all major drugs of abuse12. Following prolonged abstinence, cues previously associated with drug 
taking trigger glutamate release from prefrontal cortex and amygdala afferents to the NAc core, 
leading to reinstatement of drug use13.  
Glutamate exerts its actions through two families of receptors, the ionotropic glutamate (iGlu) 
and metabotropic glutamate (mGlu) receptors. The iGlu receptors are multimeric ligand-gated 
ion channels that open in response to glutamate and mediate fast excitatory synaptic responses at 
glutamatergic synapses. The mGlu receptors are G protein-coupled receptors that modulate 
synaptic glutamatergic activity and constitute excellent targets for drug development14,15. There 
are eight mGlu subtypes, classified into three groups based on sequence homology, 
pharmacology, and signal transduction mechanism. The group II mGlus (metabotropic glutamate 
receptor subtype 2 [mGlu2] and metabotropic glutamate receptor subtype 3 [mGlu3]) are 
Gαi/o-coupled, negatively regulate the activity of adenylyl cyclase16, are presynaptically localized 
at glutamatergic synapses where they inhibit glutamate release, and play a key role in 
maintaining glutamate homeostasis17. The group II mGlu receptors are abundantly expressed in 
brain regions implicated in different aspects of drug abuse and dependence, including the cortex, 
hippocampus, striatum, and amygdala18. Chronic psychostimulant administration alters group II 
mGlu function8, as well as their regulation by cysteine/glutamate exchange in the NAc, inducing 
profound changes in glutamatergic neurotransmission that are critically involved in the 
perpetuation of drug dependence19. Notably, chronic nicotine exposure downregulates mGlu2/3 
function in the mesolimbic system20, indicating direct involvement of these receptors in the 
development of nicotine addiction. Further support for the specific role of mGlu2 in the 
development of addiction to several drugs of abuse comes from studies in mGlu2 knockout mice, 
which have increased alcohol consumption and preference21. In addition, studies in rats 
harboring a mutation in the mGlu2 gene (GRM2 Cys407*), resulting in mGlu2-null rats, display 
increased alcohol preference and consumption22. Furthermore, multiple lines of evidence indicate 
that increasing mGlu2 activity using agonists or PAMs decreases self-administration of nicotine, 
as well as cue-induced reinstatement of psychostimulant seeking [reviewed in 19,23]. Importantly, 
mGlu2 agonists and PAMs show almost identical efficacy toward the abuse-related effects of 
several different types of psychostimulants in preclinical animal models, suggesting that mGlu2 
PAMs would be effective medications for treating nicotine addiction23.  
Only one mGlu2 PAM (AZD8529) has been tested in the clinic for nicotine cessation, but its 
severe dose-limiting toxicity prevented dosing at predicted efficacious dose levels, and proof-of-
mechanism was not achieved. SBP-9330 is structurally distinct from AZD8529 and has a 
different and improved safety profile compared to AZD8529. Thus, we expect to be able to dose 
humans at or above predicted efficacious doses and test the true potential of this mechanism for 
treating nicotine addiction.  


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A detailed description of the chemistry, preclinical pharmacology, nonclinical toxicology and 
pharmacokinetics (PK) of SBP-9330 is provided in the Investigator’s Brochure. 
SBP-9330 is being evaluated as an aid to smoking cessation. To this end, the present study is 
being conducted to evaluate the safety and tolerability of single and multiple doses of SBP-9330 
in healthy nonsmokers and healthy smokers. The study will also evaluate the PK profile of 
SBP-9330 in both populations. In addition, the feasibility of incorporating smoking-related 
assessments will be explored in healthy smokers. SBP-9330 has not been administered to 
humans prior to this study. 
 
Background 
 Mechanism of Action 
Positive allosteric modulators (PAMs) of mGlu2 represent a new class of drugs being developed 
as aids to smoking cessation. Medications that activate mGlu2 receptors can be effective via a 
dual mechanism: a) by reversing the acute effects of nicotine, thus, decreasing drug 
reinforcement, and b) by restoring glutamatergic function to normal levels, thus preventing 
relapse to drug use. 
 Preclinical Experience 
Detailed information concerning the preclinical studies conducted with SBP-9330 can be found 
in the Investigator’s Brochure. A summary is included below: 
SBP-9330 is a potent and selective mGlu2 PAM that shows acute and chronic efficacy in two 
well-established rat models of nicotine dependence: the nicotine intravenous self-administration 
(IVSA) model and the cue-induced reinstatement of nicotine seeking model. It has excellent 
drug-like properties, including oral bioavailability, metabolic stability, safety profile and is 
well-tolerated in pivotal (GLP) 14-day repeat dose toxicology studies in rats and dogs, with a 
no-adverse effect level (NOAEL) of 600 mg/kg/day and 200 mg/kg/day, respectively.  
Primary in vitro pharmacology data show that SBP-9330 is a mGlu2 receptor PAM with a 
potency of 23 nM on human and 45 nM on rat mGlu2 receptors. SBP-9330 is selective for 
mGlu2, with approximately 100-fold lower potency at mGlu3 as well as other mGlu receptor 
subtypes. SBP-9330 was tested for off-target activity against a panel of 72 human central 
nervous system (CNS) targets including G protein-coupled receptors, ion channels and 
transporters. The only finding was 70% inhibition of cholecystokinin 2 receptor (CCK2) at 
10 µM SBP-9330. This level of weak binding did not suggest any obvious safety concerns. 
The primary in vivo pharmacology data showed that SBP-9330 had acute and chronic efficacy in 
rat models of both nicotine dependence and relapse without affecting natural reward. In the acute 
nicotine IVSA model, SBP-9330 at doses of 40 mg/kg and 60 mg/kg (p.o.) reduced nicotine 
IVSA by approximately 25 and 45%, respectively. These results are comparable to the published 
effects of varenicline, which showed a 50%–70% reduction in nicotine IVSA at single doses of 
2.5–3 mg/kg (highest doses tested)24-28. Unlike SBP-9330, however, varenicline reduced food 
intake in rats at the highest dose28. 
SBP-9330 is highly bound to plasma protein from multiple species. In addition, SBP-9330 is also 
highly bound to rat brain tissue. The metabolite identification showed an identical pattern of 


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putative metabolites in all 5 species including human as well as rat and dog used in toxicology 
studies.  
In vivo, SBP-9330 was dosed to fasted Wistar rats and beagle dogs. SBP-9330 showed excellent 
oral bioavailability. 
The toxicology program for SBP-9330 was designed to support the proposed clinical study in 
healthy nonsmokers and in healthy smokers. The rat and dog were chosen as the appropriate 
species for toxicity studies based on (a) the similarity of the respective in vitro metabolic profiles 
to human, and (b) pharmacologic relevance of the rat as the in vivo efficacy model. The pivotal 
toxicity studies used the same Good Manufacture Practice (GMP) manufactured batch of 
SBP-9330 sodium salt with the identical impurity profile intended for the planned clinical study. 
Completed toxicity studies include a series of repeat-dose and genetic toxicity studies. In 
addition, safety pharmacology studies evaluating the impact of administration of SBP-9330 on 
the cardiovascular, respiratory and central nervous systems were also completed. In addition, an 
exploratory 12-week testicular toxicity study was carried out in male Wistar rats to assess the 
potential of SBP-9330 to cause reproductive effects in males and a combination 14-day rat 
SBP-9330-nicotine safety study was conducted to assess whether there is an interaction between 
SBP-9330 and nicotine. The genotoxicity of SBP-9330 was evaluated in in vitro bacterial reverse 
mutation and mammalian micronucleus assays (see Table 4). 


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Table 4 
Toxicity Data of SBP-9330 in Non-GLP Studies 
Non-GLP Studies 
4-Day Tolerability Study in male Rat 
Well-tolerated up to 1000 mg/kg 
14-Day Dose-Range Finding Tox in Rat 
Well-tolerated up to 600 mg/kg 
12-Week Testicular Toxicology in male Rat 
Well-tolerated up to 300 mg/kg 
7-Day Tolerability Study in Dog 
Well-tolerated at 1000 mg/kg 
14-Day Dose-Range Finding Tox in Dog 
Well-tolerated up to 600 mg/kg 
hERG (Manual Patch Clamp) 
IC50 = 47 µM 
Bacterial Mutagenesis (Ames II) 
No Activity 
IND-enabling GLP Studies 
14-Day Definitive Toxicology in Rat 
NOAEL = 600 mg/kg 
14-Day Definitive Toxicology in Dog 
NOAEL = 200 mg/kg 
CNS Safety Pharmacology in Rat (Irwin) 
Safe at 600 mg/kg 
Cardiovascular & Respiratory Safety Pharmacology in Dog 
Safe at 600 mg/kg 
Bacterial Mutagenesis (5 strain Ames) 
Not mutagenic 
Micronucleus in TK6 cells  
Not genotoxic 
hERG (Manual Patch Clamp) 
IC50 = 51 µM 
14-Day SBP-9330 and Nicotine Combination Toxicology in 
Rats 
NOAEL = 600 mg/kg SBP-9330 in 
combination with 0.3 mg/kg nicotine 
Abbreviations: CNS = central nervous system; hERG = human ether-à-go-go-related gene; GLP = good laboratory 
practice; NOAEL = no-observed-adverse-effect level 
The high doses for the pivotal (GLP) repeat-dose rat and dog toxicity studies were chosen based 
on the maximum tolerated dose defined in the dose range-finding studies. At the highest dose in 
the pivotal (GLP) repeat-dose studies, toxicity was characterized by poor tolerability without 
specific organ toxicity. In the 14-day pivotal (GLP) toxicity study in rats, doses up to 
600 mg/kg/day were well tolerated. Treatment-related findings were limited to minor clinical 
pathology alterations in glucose, albumin, total protein, A/G ratio, triglycerides and cholesterol 
(total and HDL), and liver, adrenal gland and spleen weight increases without histopathologic 
correlates. Based on these findings, the NOAEL of SBP-9330 in rats was determined to be 
600 mg/kg/day. At 600 mg/kg/day, the systemic exposure (AUC) values on study day 14 were 
635,000 and 2,240,000 hr.ng/mL for males and females, respectively. 
In the SBP-9330-nicotine combination study, Wistar rats were administered different 
combinations of SBP-9330 vehicle or SBP-9330 at 60, 120, 300, and 600 mg/kg/day, followed 
by a subcutaneous injection of nicotine vehicle or nicotine at 0.3 mg/kg/day. No interactions 
between SBP-9330 and nicotine were observed in the toxicity or exposure of either SBP-9330 or 
nicotine. The toxicity of SBP-9330 in this combination study was similar to that observed in the 
14-day definitive rat toxicity study with SBP-9330. The findings in this combination study 
included non-adverse increases in the mean liver to body weight ratios, minimal diffuse 
hepatocellular hypertrophy, increases in albumin, albumin to globulin ratios, cholesterol, 


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creatinine, glucose and HDL and decreased LDL following treatment. The clinical chemistry 
findings were within historical control values and were completely reversible following the 
4-week recovery period; the liver weight changes were also reversible and the liver findings were 
considered non-adverse adaptive changes without correlative changes in markers of liver injury 
(ALT, AST, GGT). SBP-9330 dosed orally at 600 mg/kg/day with a nicotine injection on Day 14 
showed Cmax and AUClast for the males at 63,500 ng/mL and 904,000 hr*ng/mL, respectively, 
and for the females at 198,000 ng/mL and 2,210,000 hr*ng/mL, respectively. Nicotine 
administered subcutaneously at 0.3 mg/kg/day with SBP-9330 (Group 7) on Day 14 showed Cmax 
and AUClast for the males at 68.1 ng/mL and 94.3 hr*ng/mL, respectively, and for the females at 
73.9 ng/mL and 109 hr*ng/mL, respectively. 
In the 14-day pivotal (GLP) toxicity study in dogs, doses of > 600 mg/kg/day were not tolerated. 
At > 600 mg/kg/day, treatment-related findings included salivation, vomiting, 
diarrhea, lethargy, and body weight loss. At this dose, the alterations in clinical pathology, 
relative organ weight changes and the histopathologic observation limited to lymphoid depletion 
in the thymus were considered secondary in nature to a general stress-related response due to the 
poor tolerability at > 600 mg/kg/day. At 200 mg/kg/day, SBP-9330 was generally well tolerated 
with treatment-related findings limited to occasional episodes of salivation and vomiting. Based 
on these findings, the NOAEL in dogs was determined to be 200 mg/kg/day. At 200 mg/kg/day, 
the systemic exposure (AUC) on study day 14 was 382,000 and 430,000 hr.ng/mL for males and 
females, respectively.  
In the in vitro genetic toxicity assays, SBP-9330 was negative for mutagenic and genotoxic 
potential up to the highest testable concentration under the test conditions of the assays. 
Moreover, SBP-9330 at doses up to 300 mg/kg/day for 12 weeks in male Wistar rats was well-
tolerated with no evidence of testicular toxicity based on an evaluation of sperm parameters and 
histopathological evaluation of the testis/secondary sex organs. 
Lastly, SBP-9330 showed low potency to functionally inhibit the cardiac ion channel 
ether-a-go-go (hERG) with an IC50 of 51 µM. SBP-9330 had no adverse effects on the nervous 
system of conscious rats or on cardiovascular and respiratory functions in conscious dogs.  
In conclusion, SBP-9330 has a low order of toxicity. SBP-9330 is neither mutagenic nor 
genotoxic. In repeat-dose toxicity studies in rats and dogs, toxicity was defined by the lack of 
oral tolerability with no evidence of systemic target organ toxicity while achieving high systemic 
exposure. The NOAEL following 14 daily doses was determined to be 600 mg/kg/day and 
200 mg/kg/day in rats and dogs, respectively. The safety profile of SBP-9330 achieved in the 
toxicity studies supports the proposed clinical studies as outlined. 
 Clinical Experience 
SBP-9330 has not been evaluated in any clinical setting.  
 
Rationale for Study Design and Dose Selection 
This study is a first-in-human study designed to explore the safety, tolerability, and 
pharmacokinetic profile of SBP-9330 in healthy human subjects over a range of doses 
anticipated to have biologic effect in humans based on the drug’s preclinical pharmacology. 
Healthy male and female adult volunteers (nonsmokers and smokers) will be enrolled. 


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The proposed starting dose in the single ascending dose (SAD) study was derived from the 
NOAEL determined in the pivotal (GLP) 14-day repeat-dose toxicology studies in rats and dogs, 
corresponding to a human equivalent dose (HED) of 96 mg/kg and 108 mg/kg, respectively. The 
maximum recommended starting dose (MRSD) of SBP-9330 was calculated to be approximately 
600 mg/day (Table 5) in accordance with European Medicines Agency (EMA) guideline on 
strategies to identify and mitigate risks for first-in-human and early clinical trials with 
investigational medicinal products (EMEA/CHMP/SWP/28367/07 Rev. 1, July 2017) and U.S. 
FDA guidance for industry for estimating the maximum safe starting dose initial clinical trials 
for therapeutics in adult healthy volunteers (CDER, July 2005).  
Table 5 
Calculations of the Maximum Recommended Starting Dose of SBP-9330 in First 
in Human Clinical Trials in Adult Healthy Volunteers 
Species 
NOAEL (mg/kg)  
HED (mg/kg)1  
MRSD (mg/day)2 
Rat 
600 
96 
576 
Dog 
200 
108 
648 
Abbreviations: NOAEL = no observed adverse effect level; HED = human equivalent dose; MRSD = maximum 
safe human starting dose 
1animal NOAEL in mg/kg × 0.16 (rat), 0.54 (dog) 
2HED × 60 kg human subject ÷ Safety Factor of 10 
The nonclinical safety data of SBP-9330 support a safe human starting dose of 576 mg/day, 
which is approximately 4-fold higher than the proposed starting dose of 150 mg in this study 
(Phase 1 Study SBP-9330-101). This starting dose will provide a 40-fold safety margin and is 
also expected to result in an exposure lower than the anticipated therapeutic exposure. 
 
Benefit/Risk Assessment 
Although SBP-9330 has not been administered to humans previously, the potential risks to 
human subjects associated with SBP-9330 are detailed in the Summary of Data and Guidance for 
the Investigator within the Investigator’s Brochure. 
Considering the 40-fold safety factor based on the 2-week NOAEL values of rat and dog and the 
projected starting human therapeutic dose range of SBP-9330 of 300-600 mg/day, the proposed 
starting dose of 150 mg/day is not expected to induce any potential risk or benefit to subjects 
participating in this study.  
In addition to specific safety stopping criteria (Section 3.5), dose-escalation PK stopping criteria 
will be implemented such that systemic exposures in subjects do not exceed 1/10th of the 
AUC0-24hr and Cmax levels associated with the identified NOAEL of the GLP 14-day rat study.  
Routine clinical assessments including hematology, chemistry, and urinalysis will be performed 
as a means of monitoring subject safety. Potential safety considerations were limited to minor 
clinical pathology alterations in glucose, albumin, total protein, triglycerides and cholesterol 
(total and HDL) based on nonclinical safety assessments. As such, subjects will be monitored for 
adverse effects related to these parameters. 
Overall, the safety monitoring practices employed by this protocol (i.e., physical examination, 
12-lead electrocardiogram (ECG), vital signs (including orthostatic blood pressures and pulse 


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rate), clinical laboratory tests, Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire, 
and AEs) are adequate to protect the subjects’ safety and should detect all expected treatment-
emergent AEs (TEAEs).  
There will be no direct health benefit for study participants from receipt of the study drug. An 
indirect health benefit to the healthy subjects enrolled in this trial is the free medical tests 
received at Screening and during the study. 


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
OBJECTIVES 
ENDPOINTS 
Primary 
 
To assess the safety and tolerability of single 
and multiple ascending oral doses of SBP-9330 
in healthy nonsmokers and healthy smokers 
 
• 
Incidence and severity of adverse events 
(AEs) for subjects administered SBP-9330 
compared to placebo 
• 
Changes in vital signs, physical 
examination findings, ECG findings, 
C-SSRS questionnaire results, and clinical 
laboratory results for subjects administered 
SBP-9330 compared to placebo 
Secondary 
 
To determine single and multiple oral dose 
pharmacokinetics (PK) of SBP-9330 in healthy 
nonsmokers and healthy smokers 
Single Ascending Dose (SAD) Phase 
The main PK endpoints for the SAD phase are the 
following PK parameters: 
• 
Cmax, Tmax, AUC0-24, AUC0-T, AUC0-∞, Thalf, 
CL/F, and Vz/F  
Multiple Ascending Dose (MAD) Phase 
The main PK endpoints for the multiple ascending 
dose (MAD) phase are the following PK parameters: 
• 
Cmax, Tmax, Ctrough, Cτ, AUC0-24 or AUCτ, 
AUC0T, effective Thalf, CL/Fss, Vz/Fss, 
RAC(Cmax), and RAC(AUC) 
For all study phases, additional PK parameters (as 
noted in Section 8.4) may be estimated as appropriate 
to support the main PK endpoints. 
To explore the effect of food on the single oral 
dose PK of SBP-9330 in healthy nonsmokers 
The main PK endpoints to assess the effect of food 
after a single oral dose of 600 mg SBP-9330 to 
healthy nonsmokers are the following: 
• 
Cmax, AUC0-t, and AUC0-∞; Tmax will also be 
evaluated 
Additional PK parameters may be estimated as 
appropriate to support the main PK endpoints 
(Section 8.4). 
Exploratory 
 
To explore the effect of SBP-9330 on 
smoking-related assessments  
• 
Expired carbon monoxide (ECO) level  
• 
Plasma cotinine level 
• 
Number of cigarettes smoked (smoking log) 
• 
Minnesota Nicotine Withdrawal Scale 
(MNWS) responses 


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OBJECTIVES 
ENDPOINTS 
• 
Questionnaire on Smoking Urges – Brief 
version (QSU-Brief) responses 


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3. 
STUDY DESIGN 
 
Adaptive Features and Risk Management of Study Design 
The rationale for the following adaptive features is based on taking an iterative, 
hypothesis-forming approach in this clinical trial. The following categories will be adapted as 
shown in Table 6. 
Table 6 
Adaptive Features and Boundaries 
Adaptive study 
design category 
Adaptive Features 
Boundaries 
Dose level for the 
SAD cohorts 
SAD dose levels may be 
adjusted based on safety 
and available PK data 
reported in the previous 
cohort(s). 
Doses are intended to escalate; however, they 
may be adjusted to an intermediate (lower) or 
equivalent dose, based on safety and available PK 
data reported in the previous cohort(s). 
Escalation from one dose level to the next dose 
level will not be more than 3-fold the previous 
dose. 
Dose level for the 
MAD cohorts 
Doses for the MAD 
cohorts will be adapted in 
accordance with safety 
and available PK data 
collected in previous 
cohorts during the SAD or 
MAD phase. 
The first MAD dose must be lower or equal to a 
dose administered in a SAD cohort for which 
safety and PK data are available. 
Doses are intended to escalate; however, they 
may be adjusted to an intermediate (lower) or 
equivalent dose, based on safety and available PK 
data reported in the previous cohort(s). 
Escalation from one dose level to the next dose 
level will not be more than three-fold the previous 
dose. 
A MAD daily dose level cannot be higher than the 
highest dose level tested in SAD.  
Dose level for the 
Smoker cohorts 
Smoker cohort dose levels 
will be adapted in 
accordance with safety 
and available PK data 
collected in previous 
cohorts during the SAD or 
MAD phase. 
The first Smoker dose must be lower or equal to a 
dose administered in a MAD cohort for which 
safety and PK data are available. 
Doses are intended to escalate; however, they 
may be adjusted to an intermediate (lower) or 
equivalent dose, based on safety and available PK 
data reported in the previous cohort(s). 
Escalation from one dose level to the next dose 
level will not be more than three-fold the previous 
dose. 
A Smoker cohort daily dose level cannot be 
higher than the highest dose level tested in the 
MAD phase. 
Dosing frequency for 
the MAD and 
Smoker cohorts 
The dosing frequency 
may be modified from 
once daily to twice daily. 
The modification from once daily to twice daily 
administration will not change the total daily dose 
outlined in this protocol. 
The quantity of 
cohorts in each phase 
(SAD or MAD) 
The quantity of cohorts 
may be decreased.  
The maximum number of cohorts for the SAD 
and MAD phase are 5 and 4, respectively. 
The number of cohorts in each phase may be 
decreased at the discretion of the Sponsor 


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Adaptive study 
design category 
Adaptive Features 
Boundaries 
depending on the emerging safety and PK data 
from the previous cohorts. 
The quantity of 
cohorts during the 
Smoker phase 
A 3rd cohort may be 
added. 
The Smoker phase will have a maximum of 
3 cohorts. There are 2 planned cohorts and an 
additional cohort may be added depending on the 
emerging PK and safety data in the previous 
cohorts. 
Overlap between 
SAD and MAD 
phases 
The MAD phase of the 
study may commence in 
parallel to the SAD or 
thereafter.  
The decision on how early the MAD phase of the 
study may start and the doses to be administered 
will be determined by the Sponsor after 
consultation with the DSMB based on emerging 
safety and PK data. 
A MAD dose level cannot be higher than the last 
dose level administered in the SAD phase.  
Blood collection 
during the MAD 
phase 
The PK blood sampling 
timepoints during the 
MAD phase may be 
modified. 
Depending on data obtained during the SAD 
phase, the PK sampling timepoints during the 
MAD phase may be modified in order to optimize 
characterization of PK parameters of interest. 
Food-Effect cohort 
The food-effect cohort 
may be done in a cohort 
with a dose level other 
than 600 mg. 
Depending on data obtained in the previous 
cohorts, the food-effect may be evaluated at a 
dose level other than 600 mg to optimize 
characterization of PK parameters of interest. 
Abbreviations: DSMB = Data and Safety Monitoring Board; MAD = multiple ascending dose; 
PK = pharmacokinetic; SAD = single ascending dose 
The decision-making process for the above adaptive study categories will be as follows, unless 
otherwise stated: 
• Interim review of safety and emerging PK data for SBP-9330 from completed or ongoing 
SAD, MAD, or Smoker cohorts in a blinded fashion by the Data and Safety Monitoring 
Board (DSMB). For Part C (Smoker Phase), the DSMB will be provided the 
randomization code to aide in the review of safety and PK data. 
• Outcome on the adaptive study category will be documented by the DSMB. 
Based on the above, progression to the next dose cohort may be performed without delay (i.e., 
without prior approval from the Institutional Review Board (IRB) or regulatory authorities), 
unless the adaptive features are outside of the pre-specified boundaries. If it is anticipated to 
progress with adaptive features outside of the pre-specified boundaries, prior approval must be 
granted by the IRB and regulatory authorities.  
 Data and Safety Monitoring Board (DSMB)  
A DSMB will be established to assure that the safety of the study subjects is protected while the 
scientific goals of the study are being met. Specifically, the DSMB is charged with monitoring 
the safety of participants and the quality of the data, as well as the appropriate termination of 
studies when risks have been uncovered or when it appears that the clinical trial cannot be 


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concluded successfully. The DSMB is responsible for reviewing and evaluating safety and 
available plasma PK data collected after each cohort. 
The DSMB will be comprised of voting members who are independent of the Sponsor and CRU 
and will, at a minimum, include physicians experienced in drug safety.  The composition and 
operations of the DSMB will be detailed in a separate document that will serve as the Data and 
Safety Monitoring Plan (DSMP). 
The DSMB will review safety data up to discharge and available plasma PK data of all the 
subjects in the respective cohort in a blinded manner to provide recommendations to the Sponsor 
and PI whether to escalate doses between cohorts. The minimum number of subjects required to 
decide on dose escalation is six subjects (i.e., at least four on active treatment) for Part A (SAD) 
and eight subjects (i.e., at least six on active treatment) for Parts B (MAD) and C (Smoker).  
The DSMB will also advise as to when MAD dosing may commence and whether any stopping 
criteria were met. For Part A and Part B, these assessments will generally be made without 
breaking the blinded randomization code. For Part C, the DSMB will be provided the 
randomization code to aide in the review. If judged necessary by the DSMB, an individual or the 
complete cohort may be unblinded during evaluation of the study data. Before unblinding, a 
decision should be made about the action to be taken based on the revealed treatment allocation. 
The DSMB may adjust the dose based on the treatment-emergent safety and available PK data.  
 
Overall Study Design 
This is a single-center, first-in-human, randomized, double-blind, placebo-controlled, single- and 
multiple-dose escalating study incorporating a food-effect cohort. 
The study will include 3 parts: 
• Part A: SAD phase with a nested food-effect cohort 
• Part B: MAD phase 
• Parc C: Smoker phase 
Each cohort will receive SBP-9330 in an ascending dose order or until stopping rules as outlined 
in Section 4.3.2 are met. 
Part A – SAD phase with nested food-effect cohort will include approximately 40 subjects 
(5 cohorts of 8 subjects), Part B – MAD phase will include approximately 40 subjects (up to 
4 cohorts of 10 subjects), and Part C – Smoker phase will include approximately 30 subjects (up 
to 3 cohorts of 10 subjects). Therefore, up to 110 subjects will be included in the study. 
All subjects who complete the study and those terminating early will be required to complete the 
End of study (EOS)/Follow up procedures. 
The End of Trial will correspond to the last patient last visit of the study. 
 Part A – SAD Phase with Nested Food-Effect Cohort 
Screening of participants will occur within approximately 28 days of the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 


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consent to participation will be admitted to the CRU for baseline evaluations before dosing 
(Day -1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. Subjects in Cohort A3 will have eligibility confirmed for Day -1 for fasted 
dose (Period 1) only and not for the fed dose (Period 2). 
Eligible subjects will be randomized to SBP-9330 or placebo in 1 of the 5 ascending dose 
cohorts (8 subjects per cohort) to have a total of 6 subjects receiving SBP-9330 and 2 subjects 
receiving placebo. All cohorts in the fasting state will be dosed according to a sentinel dosing 
design to ensure optimal safety. Initially, 2 subjects will be dosed; 1 subject will be dosed with 
SBP-9330 and 1 subject with placebo. If the safety and tolerability results of the first 24 hours 
following dosing for the initial subjects are acceptable to the Investigator, the other 6 subjects 
(5 active and 1 placebo) may be dosed approximately 24 hours after dosing of the sentinel group.  
Furthermore, one single-dose, two-period, crossover, food-effect cohort will be integrated into a 
SAD cohort (Cohort A3). 
The proposed SAD design and planned escalation are presented in Table 7. 


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Table 7 
Part A – SAD Phase with Nested Food-Effect Cohort Design and Dose Levels 
Cohort 
N (active:placebo) 
Dose (mg) 
Drug administration 
A1 
6:2  
(1:1 [sentinel group] and 
5:1 [remaining subjects])  
150 mg 
(1 × 150-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose administration 
of SBP-9330 or placebo under 
fasting conditions on Day 1. 
A2 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
300 mg 
(1 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose administration 
of SBP-9330 or placebo under 
fasting conditions on Day 1. 
A31 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects] 
for Period 1 only) 
600 mg 
(2 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose administration 
of SBP-9330 or placebo under 
fasting conditions on Day 1 of 
Period 1 and fed conditions on 
Day 1 of Period 2. Washout 
between the 2 periods will be 
at least 7 to 14 days. 
A4 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
1200 mg 
(4 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose administration 
of SBP-9330 or placebo under 
fasting conditions on Day 1. 
A5 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
2400 mg 
(8 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose administration 
of SBP-9330 or placebo under 
fasting conditions on Day 1. 
1 2-period, food-effect cohort 
For Cohorts A1, A2, A4, and A5, each subject will receive the assigned treatment (SBP-9330 or 
placebo) under fasting conditions.  
For Cohort A3 (2 period food-effect cohort), each subject will receive the randomly assigned 
treatment (SBP-9330 or placebo) under fasting conditions in Period 1. After a 7- to 14-day 
washout period, they will receive the same single dose of SBP-9330 or placebo in a fed state in 
Period 2, 30 minutes after the start of an FDA High-Fat and High-Calorie Breakfast. Escalation 
to Cohort A4 will be based only on the fasting period safety and PK and may proceed in parallel 
to the A3 fed period. 
All cohorts in the fasting state will be dosed according to a sentinel dosing design to ensure 
optimal safety. Initially, 2 subjects will be dosed; 1 subject will be dosed with SBP-9330 and 1 
subject with placebo. If the safety and tolerability results of the first 24 hours following dosing 
for the initial subjects are acceptable to the Investigator, the other six subjects (5 active and 1 
placebo) may be dosed approximately 24 hours after dosing of the sentinel group.  


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Escalation to the next higher dose will only proceed if none of the stopping criteria have been 
reached and when the safety and tolerability and plasma PK analysis of the previous dose, 
including delayed emergence of significant AEs in earlier cohorts, are acceptable to the 
Investigator, Sponsor and DSMB. 
The SAD phase will have a maximum of 5 cohorts. The number of cohorts may be changed at 
the discretion of the Sponsor depending on the emerging safety and plasma PK data from the 
previous cohorts. The dose levels proposed for SAD cohorts may be adjusted during the course 
of the study based on preliminary safety and plasma PK data but escalation will not be more than 
3-fold the previous dose. 
For Cohorts A1, A2, A4, and A5:  
• Subjects will be confined to the CRU from at least 10 hours prior to drug administration 
until approximately 48 hours after study drug administration. Subjects will therefore be 
confined for 4 days and 3 nights (Day -1 to Day 3). However, they may be advised to stay 
longer at the CRU for safety reasons, if judged necessary by an Investigator. 
• Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 8±1). 
• Total study duration: up to 38 days (including Screening) 
For Cohort A3 (food-effect cohort):  
• In each period, subjects will be confined to the CRU from at least 10.5 hours prior to 
drug administration until approximately 48 hours after study drug administration. 
Subjects will therefore be confined for 4 days and 3 nights (Day -1 to Day 3) in each 
period. However, they may be advised to stay longer at the CRU for safety reasons, if 
judged necessary by an Investigator. 
• Washout period between treatment administrations: at least 7 to 14 calendar days 
• Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 8±1) of Period 2. 
• Total study duration: up to 46 days (including Screening) 
The schedule of activities of the SAD Phase of the study is described in Table 1. 
 Part B - MAD Phase 
Screening of participants will occur within approximately 28 days prior to the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 
consent to participation will be admitted to the CRU for baseline evaluations before dosing 
(Day -1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. 
Subjects will be randomized to SBP-9330 or placebo in 1 of the 3 ascending dose cohorts 
(10 subjects per cohort in 4:1 [SBP-9330:placebo] ratio) to have a total of 8 subjects receiving 
SBP-9330 and 2 subjects receiving placebo. An additional MAD cohort (Cohort B4) may be 


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added at the discretion of the Sponsor depending on emerging safety and PK data from previous 
cohorts. 
The proposed MAD design and planned escalation are presented in Table 8. 
Table 8 
Part B - MAD Phase Design and Dose Levels 
Cohort 
N 
(active:placebo) 
Dose  
Drug administrations 
B1 
8:2 
adaptive  
Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
B2 
8:2 
adaptive  
Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
B3 
8:2 
adaptive  Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
Additional 
B4 
8:2 
adaptive 
Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
Each subject will receive once daily oral administration of the assigned treatment and dose under 
fasting conditions (SBP-9330 or placebo) for 14 consecutive days.  
The MAD phase of the study may commence in parallel to the SAD or thereafter. The decision 
on how early the MAD phase of the study may be started and the doses to be administered will 
be determined by the Sponsor after consultation with the DSMB based on emerging safety and 
PK data. The first MAD daily dose will be less than or equal to an already well-tolerated SAD 
dose for which complete safety and PK data are available.  
All relevant safety and available plasma PK data will be reviewed by the DSMB before any dose 
escalation. The dose levels proposed for MAD cohorts may be adjusted during the course of the 
study based on preliminary safety and PK data. The dosing frequency may also be changed from 
once daily to twice daily, without changing the total daily dose outlined in the protocol.  
The MAD phase will have a maximum of 4 cohorts. The number of cohorts may be changed at 
the discretion of the Sponsor depending on the emerging safety and PK data from the previous 
cohorts. The increase from one dose level to the next dose level will not be more than 3-fold. A 
MAD daily dose level cannot be higher than the highest dose level tested in SAD.  
Subjects will be confined to the CRU from at least 10 hours prior to drug administration until 
approximately 48 hours after last study drug administration. Subjects will therefore be confined 
for 17 days and 16 nights (Day -1 to Day 16). 
Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 21±1). 
The schedule of activities of the MAD Phase of the study is described in Table 2. 


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 Part C - Smoker Phase 
Screening of participants will occur within approximately 28 days prior to the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 
consent to participation will be admitted to the CRU for baseline evaluations before dosing 
(Day -1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. 
Subjects will be randomized to SBP-9330 or placebo in 1 of the 2 planned Smoker cohorts 
(10 subjects per cohort in 4:1 [SBP-9330:placebo] ratio) to have a total of 8 subjects receiving 
SBP-9330 and 2 subjects receiving placebo. An additional Smoker cohort (Cohort C3) may be 
added at the discretion of the Sponsor depending on emerging safety and PK data from previous 
cohorts. 
The proposed Smoker phase design and planned escalation are presented in Table 9. 
Table 9 
Part C - Smoker Phase Design and Dose Levels 
Cohort 
N (active:placebo) 
Dose  
Drug administrations 
C1 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
C2 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
Optional C3 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days 
Each subject will receive once daily oral administration of the assigned treatment and dose under 
fasting conditions (SBP-9330 or placebo) for 14 consecutive days.  
The Smoker phase of the study may commence after completion of dosing the MAD phase of the 
study. The Smoker cohort daily dose will be less than or equal to highest MAD dose for which 
complete safety and PK data are available.  
All relevant safety and available plasma PK data will be reviewed by the DSMB before any dose 
escalation. The DSMB will be provided the randomization code to aide in the review for Part C. 
The dose levels proposed for Smoker cohorts may be adjusted during the course of the study 
based on preliminary safety and PK data.  
The Smoker phase will have a maximum of 3 cohorts. The number of cohorts may be changed at 
the discretion of the Sponsor depending on the emerging safety and PK data from the previous 
cohorts.  
Subjects will be confined to the CRU from at least 10 hours prior to drug administration until 
approximately 48 hours after last study drug administration. Subjects will therefore be confined 
for 17 days and 16 nights (Day -1 to Day 16). 
Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 21±1). 


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The schedule of activities of the Smoker Phase (Part C) of the study is described in Table 3. 
 
Study Treatments 
The following investigational products (IPs) will be administered according to the outlined dose 
levels in Sections 3.3.1 and 3.3.2. 
• Test product: SBP-9330 75-mg, 150-mg and 300-mg capsules  
• Placebo: Placebo to match SBP-9330 75-mg, 150-mg and 300-mg capsules 
 
Dose Escalation and Stopping Rules 
Escalation to the next higher dose will only proceed if none of the stopping criteria below have 
been reached and when the safety and tolerability and plasma PK analysis of the previous dose, 
including delayed emergence of significant AEs in earlier cohorts, are acceptable to the 
Investigator, Sponsor and DSMB.  Dose escalation will be stopped if it is determined that the 
limits of safety and/or tolerability or the PK stopping criteria (Section 3.5.2) have been reached.  
This decision will be made by the Sponsor and the Principal Investigator based on DSMB 
recommendation.  If dose escalation is stopped due to any findings, additional cohorts may 
receive the same or lower doses of the investigational compound. However, in the event that the 
findings are likely related to Cmax, dose escalation may continue by dividing the dose ensuring 
that the Cmax is the same or lower. 
 Individual Subject Stopping Rules 
Participation in the clinical study may be discontinued by the Principal Investigator or by the 
Sponsor for any of the following reasons, but not limited to: 
• Any subject experiencing a confirmed drug-related moderate or severe AE or serious AE 
(SAE) will not receive the next scheduled dose of IP until a safety review of the AE is 
performed by an Investigator and Sponsor Medical Monitor. The decision to continue 
dosing must be agreed upon by both an Investigator and Sponsor Medical Monitor. 
• Any subject experiencing seizures, intractable headaches, or suicidal ideations. 
• Liver chemistry elevations that meet any of the following parameters: 
▪ ALT or AST > 3 × upper limit of normal (ULN) and total bilirubin > 2 × ULN 
without elevated alkaline phosphatase. 
▪ ALT or AST > 3 × ULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
▪ ALT or AST > 8 × ULN, which is confirmed. 
• Meets either of the following ECG criteria:  
▪ QTcF >500 ms 
▪ QTcF change from baseline >60 ms 
▪ Subject non-compliance (including any violation of protocol requirements which may 
affect the study outcome) 


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 Cohort Stopping Rules 
If any of the following safety concerns are observed, dosing of all subjects at the given dose level 
or higher will be suspended/halted and all available data will be evaluated by the DSMB.  
Dose continuation (remaining subjects within a cohort or remaining dosing for a subject) or 
escalation should not proceed for any of, but not limited to, the following reasons: 
• If one SBP-9330-related SAE occurs in a cohort 
• Severe AE at least possibly related to SBP-9330 in two or more subjects in the same 
cohort* 
• Other findings that, at the discretion of the DSMB or Sponsor, indicate further dosing 
should be stopped 
* Prior to suspending the cohort, if severe AEs are reported in two or more subjects at a given 
dose level, consideration should be given to the treatment assignment (SBP-9330 or placebo). 
After causality assessment, the Investigator (or designee) should open the individual 
randomization code to verify the treatment received. Dosing at the given dose level may continue 
if only one subject received SBP-9330 and the other(s) received the placebo. 
Subjects experiencing severe AEs will be followed up with serial measurements of the related 
clinical parameter(s), as per medical judgment, until resolution, stabilization, or until the subject 
is lost to follow-up. 
Dose escalation will be discussed during the DSMB meeting and may be stopped depending on 
Principal Investigator’s or Sponsor’s decision, based on but not limited to the following: 
• New clinically significant abnormalities in physical examination, 12-lead ECG, or vital 
signs in two or more subjects 
• Overall pattern of clinical changes or symptoms that may have appeared minor in terms 
of an individual AE or subject, but which collectively present a safety concern 
• Clinically significant changes in organ-specific laboratory parameters (e.g., liver function 
enzymes in one or more subjects) 
• Pattern of laboratory changes (e.g., a consistent increase or decrease in two or more 
subjects or within or across dosing cohorts) that might indicate an overall safety concern  
In addition to the safety stopping criteria listed above, dose-escalation PK stopping criteria will 
be implemented such that systemic exposures in subjects do not exceed 1/10th of the AUC0-24hr 
and Cmax levels associated with the identified NOAEL of the GLP 14-day rat study. The 1/10th 
stopping values for Cmax and AUC0-24hr are 25.4 µg/mL and 224 µg* hr/mL, respectively. Dose 
escalation in the SAD, MAD, or Smoker components of the study will be stopped before these 
exposures are achieved. 
 Trial Stopping Rules 
The trial can be prematurely terminated by the DSMB or Sponsor for any of the following 
reasons: 
• Occurrence of two SBP-9330-related SAEs in a cohort 


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• Occurrence of one death attributable to the study treatment 


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4. 
SUBJECT POPULATION 
Subjects meeting all the inclusion criteria and none of the exclusion criteria at Screening may be 
eligible for participation in this study. Continued eligibility will be assessed upon admission to 
the CRU, prior to the first study drug administration. 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomly assigned to the study intervention or entered in the study. 
An effort will be made to include similar proportions of males and females in the study. 
 
Inclusion Criteria 
1. Provision of written informed consent prior to the initiation of any protocol-specific 
procedures 
2. Stated willingness to comply with all study procedures and availability for the duration of 
the study 
3. Healthy male or female subject ≥ 18 and ≤ 55 years of age 
4. Body mass index (BMI) ≥ 18.5 kg/m2 and ≤ 32.0 kg/m2 
5. Body weight ≥ 50.0 kg at Screening 
6. A female subject must meet at least one of the following criteria: 
a) Is of childbearing potential and agrees to use an acceptable contraceptive method. 
Acceptable contraceptive methods include: 
• Total abstinence, in accordance with the lifestyle of the subject, from at least 
30 days prior to the first study drug administration through to at least 90 days 
after the last dose of the study drug 
• One of the following contraceptive methods, used in combination with a barrier 
method (e.g., a diaphragm, a cervical cap, or a condom), from at least 30 days 
prior to the first study drug administration through to at least 90 days after the last 
dose of the study drug: 
▪ Intrauterine device (with or without hormones) 
▪ Spermicide 
Or 
b) Is of non-childbearing potential, defined as surgically sterile (i.e., has undergone 
complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a 
postmenopausal state (i.e., at least 1 year without menses prior to the first study drug 
administration without an alternative medical condition and confirmed with a serum 
follicle-stimulating hormone [FSH] > 40 IU/L at Screening) 
7. Male subjects, if not surgically sterilized, must agree to use adequate contraception and 
not donate sperm from the first admission to the CRU until 90 days after the last study 
drug administration. Adequate contraception for the male subject (and/or his female 
partner) includes the following: 


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• Use of spermicide, hormonal contraceptives or an intrauterine device combined 
with at least one of the following forms of contraception: a diaphragm, a cervical 
cap, or a condom 
• Double-barrier method  
Total abstinence, in accordance with the lifestyle of the subject, from at least 30 days 
prior to the first study drug administration until 90 days after the last study drug 
administration, is also acceptable 
8. Parts A and B only: Never- or nonsmoker (a nonsmoker is defined as someone who 
completely stopped using nicotine products for at least 2 years prior to the first study 
drug administration) 
9. Have no clinically significant medical or mental health conditions captured in the medical 
history or evidence of clinically significant findings on the physical examination and/or 
ECG, as determined by an Investigator 
10. No clinically significant abnormalities in blood pressure, heart rate, body temperature and 
respiratory rate and no evidence of orthostatic hypotension or postural tachycardia at 
Screening as defined below: 
a) 100 mmHg ≤ systolic blood pressure (BP) ≤ 140 mmHg in supine position. 
b) 60 mmHg ≤ diastolic BP ≤ 90 mmHg in supine position. 
c) 60 beats per minute (bpm) ≤ heart rate ≤ 100 bpm in supine position. 
d) 35.5 °C ≤ body temperature ≤ 37.5 °C. 
e) 10 breaths per minute ≤ respiratory rate ≤ 22 breaths per minute. 
f)  ≥ 20 mmHg decrease in systolic BP from supine to standing. 
g) ≥ 10 mmHg decrease in diastolic BP from supine to standing. 
h) ≥ 30 bpm increase in heart rate from supine to standing. 
Part C Only: 
11. Are current tobacco cigarette smokers who smoke an average of 10 or more cigarettes per 
day in the 30 days prior to Screening  
12. Expired breath CO level ≥10 parts per million (ppm) at Screening and prior to the first 
study drug administration 
13. Positive test result for cotinine at Screening and prior to the first study drug 
administration 
14. Are not motivated to try to quit smoking from Screening and through 30 days from the 
first study drug administration 
 
Exclusion Criteria 
1. Female who is lactating 
2. Female who is pregnant according to the pregnancy test at Screening or prior to the first 
study drug administration 


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3. Female who is planning to become pregnant during this study or within 90 days after the 
last study drug administration 
4. Male with female partner who is pregnant, lactating, or planning to become pregnant 
during this study or within 90 days after the last study drug administration 
5. Poor venous access as determined by an Investigator at Screening 
6. History of significant hypersensitivity to SBP-9330 or any related products (including 
excipients of the formulations) as well as severe hypersensitivity reactions (like 
angioedema) to any drugs 
7. Presence of any medical condition that, in the opinion of an Investigator, poses an 
unacceptable risk to the subjects 
8. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that 
may affect drug absorption 
9. Evidence or history of clinically significant cardiovascular, pulmonary, hematologic, 
psychiatric (including mood and substance use disorders), neurological (including 
migraines, seizures, and epilepsy), endocrine, renal, hepatic, gastrointestinal, 
immunologic or dermatologic disease  
10. History of malignancy within the past five years, except for successfully treated basal cell 
carcinoma of the skin 
11. History of suicidal ideation or suicidal behaviour as per the C-SSRS questionnaire 
administered at Screening 
12. Evidence or history of significant psychiatric disease or any DSM-5 disorder as assessed 
by the Mini International Neuropsychiatric Interview (M.I.N.I.) administered at 
Screening 
13. Routine or chronic use of more than three grams of acetaminophen daily 
14. Strenuous activity, sunbathing, and contact sports within 48 hours prior to (first) 
admission to the CRU  
15. Current alcohol consumption exceeding two standard drinks per day on average 
(1 standard drink=10 grams of alcohol) for male subjects and one standard drink per day 
on average for female subjects 
16. History of alcohol or drug (other than caffeine) use disorder within 12 months prior to 
Screening 
17. Any clinically significant illness in the 28 days prior to the first study drug administration 
18. QTcF interval (QT interval corrected for heart rate according to Fridericia) > 450 ms for 
males and > 470 ms for females at Screening or on Day –1 
19. Parts A and B only: Positive test result for alcohol and/or drugs of abuse at Screening or 
prior to the first drug administration 
20. Positive test results for HIV-1/HIV-2 antibodies, hepatitis B surface antigen (HBsAg) or 
hepatitis C antibody (HCVAb) 


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21. Consumption of any prescription drugs (with the exception of hormonal contraceptives or 
hormone replacement therapy) or over-the-counter (OTC) medications and nutrients 
known to modulate cytochrome P450 (CYP450) enzymes activity (e.g., grapefruit or 
grapefruit juice, pomelo juice, star fruit, or Seville [blood] orange products) or St. John’s 
Wort within 14 days prior to the first study drug administration  
22. Consumption of other prescription and over-the-counter medication not specifically 
excluded by Exclusion Criterion 21 including health supplements and herbal remedies 
within 7 days prior to the first study drug administration (an exception is made for 
paracetamol [acetaminophen], which is allowed up to admission to the clinic). 
23. Any other clinically significant abnormalities in laboratory test results at Screening that 
would, in the opinion of an Investigator, increase the subject's risk of participation, 
jeopardize complete participation in the study, or compromise interpretation of study data 
24. Intake of an investigational product in the 30 days or 5 half-lives (whichever is longer) 
prior to Screening 
25. Inclusion in a previous cohort of this clinical study 
26. Employee of the contract research organization (CRO) or the Sponsor. 
27. Blood donation (excluding plasma donation) of approximately 500 mL within 56 days 
prior to Screening  
28. Plasma donation within 7 days prior to Screening 
Part C Only: 
29. History of generalized rash reaction to any drugs 
30. Positive test result (except cotinine) for alcohol and/or drugs of abuse at Screening or 
prior to the first study drug administration 
31. Use of smoking cessation aids (NRT, bupropion, or varenicline) within 30 days prior to 
the first study drug administration 
32. Unable to abstain from smoking tobacco cigarettes for at least 1 hour before and 2 hours 
after study drug administration 
33. Unable to abstain from using nicotine-containing products other than tobacco cigarettes 
(e.g., pipes, cigars, e-cigarettes or vapes, nicotine topical patches, nicotine gum, or 
nicotine lozenges) during the study 
 
Withdrawal Criteria 
 Before First Treatment Administration 
Before the first treatment administration, continuing to meet the study inclusion/exclusion 
criteria will govern which subjects are randomized to treatment. Subjects withdrawn before first 
treatment administration will not be followed up and will not undergo EOS/Follow-up 
assessments. Other safety assessments may be performed if required. 


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Subjects are free to withdraw their consent to participate in the study at any time, without 
prejudice. The reason for their withdrawal or for deciding to end their participation will be 
documented. 
 After First Treatment Administration 
Subjects may, at any time, voluntarily withdraw from the study or be removed from the study at 
the discretion of an Investigator or Sponsor. An Investigator may withdraw a subject at any time 
if it is determined that continuing the study would result in a significant safety risk to the subject 
or if their behavior is deleterious to the study environment. 
If such withdrawal occurs, or if the subject fails to return for visits, an Investigator should 
determine the primary reason for a subject’s premature withdrawal from the study and record the 
reason in the subject’s study documents.  
An Investigator may remove a subject from the study on the recommendation of the PK facility 
and/or Sponsor due to an unanticipated event that could result in an inadequately characterized 
PK profile, such as a missed blood draw, an AE, meal deviation or concomitant medication 
intake. 
Attempts should be made to have such subjects complete the EOS/Follow-up assessments. The 
EOS/Follow-up assessments should be performed as soon as possible after the last study 
treatment administration. 
The blind may be broken only in emergency situations, where knowledge of the treatment that 
the subject received is necessary for safety management (Section 5.2.4). 
Details of reasons for removal of subjects will be recorded, reported to the Sponsor and 
documented in the clinical study report. 
For subjects lost to follow-up (i.e., those subjects whose status is unclear because they fail to 
appear for study visits without stating an intention to withdraw), an investigator should show 
"due diligence" by documenting in the source documents steps taken to contact the subject, e.g., 
dates of telephone calls, registered letters, etc. 
 
Lifestyle and/or Dietary Requirements 
• Subjects will be prohibited from consuming food or beverages containing grapefruit 
and/or pomelo for 14 days prior to the first study drug administration and during the 
study. 
• Subjects will be prohibited from consuming alcohol for 48 hours prior to each admission 
to the CRU until discharge. Throughout the study, in case of any doubt about alcohol 
consumption, a test for alcohol may be performed if requested by an Investigator 
• Subjects will be prohibited from consuming food or beverages containing xanthines (i.e., 
tea, coffee, cola drinks, energy drinks or chocolate) for 48 hours prior to each admission 
to the CRU until last discharge. 
• Subjects will eat only the food provided by the CRU during confinement. 
• Female subjects of childbearing potential will have to take appropriate measures to 
prevent pregnancy from at least 30 days prior to the first study drug administration, 


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during the study and for at least 90 days after the last dose of the study drug, as described 
in Section 4.1. It is the participant’s responsibility to notify the CRU if a pregnancy 
occurs from the end of their study participation until 90 days after the last dose of the 
study drug. 
• Male subjects will be expected to use an acceptable contraceptive regimen and not to 
donate sperm from the first admission to the CRU, during the study, and until at least 
90 days after the last study drug administration, as described in Section 4.1. Reporting for 
pregnancy in female partners is detailed in Section 7.5. 
• For the Smoker cohorts, subjects will abstain from smoking tobacco cigarettes for at least 
1 hour before and 2 hours after study drug administration. Subjects will also abstain from 
using nicotine-containing products other than tobacco cigarettes (e.g., pipes, cigars, e-
cigarettes or vapes, nicotine topical patches, nicotine gum, or nicotine lozenges) or other 
tobacco products (cigars, cigarillos, pipes) during the study. 
 
Concomitant Treatment 
Except for medication which may be required to treat AEs, no other treatment or medication 
other than the study drugs will be allowed from the first dosing until all study activities and 
evaluations have been completed.  
Systemic contraceptives and hormone replacement therapy are permitted for female subjects as 
per Section 4.1. 
Subjects will be instructed to notify the CRU about any new medications taken after the start of 
the study treatment. All medications and significant non-drug therapies (including physical 
therapy and blood transfusions) administered after the subject has received the study treatment 
must be listed in the subject case report form (CRF). The drug name and dose taken will be 
noted. An investigator or delegate and/or the Sponsor will decide whether the subject will be 
permitted to remain in the study, depending on the drug used, the time of drug intake, etc. 
Subjects receiving the COVID-19 vaccine should be fully vaccinated at least 14 days prior to 
receiving Investigational Product. 


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5. 
STUDY TREATMENTS 
 
Investigational Products 
All IPs will be provided by the Sponsor. The lot number and the measured content of the dosage 
form, if available, will be included in the final report. 
 SBP-9330 
SBP-9330 75 mg, 150 mg, and 300 mg capsules are manufactured by PACE Laboratory 
(previously Velesco Pharmaceutical Services, Inc.) for oral administration. Small batches of 
75 mg dose strength capsules will also be prepared by the Altasciences pharmacy using a 
Sponsor-supplied procedure. Each white gelatin capsule contains SBP-9330 sodium equivalent 
to 75 mg, 150 mg or 300 mg SBP-9330.  
 Placebo 
Placebo capsules matched to Sponsor’s SBP-9330 75, 150 and 300 mg capsules will be supplied 
by the Sponsor. The placebo formulation will be comprised of the same white gelatin capsule, 
filled with Avicel microcrystalline cellulose, without SBP-9330 (active ingredient). 
 
Investigational Product Management 
 Packaging, Labeling and Dispensing 
The Sponsor will be responsible for ensuring that the IP is manufactured in accordance with 
applicable current Good Manufacturing Practice regulations and requirements. 
The IPs will be labeled according to the requirements of local law and legislation. The IPs will 
be dispensed by the CRU’s pharmacy. 
 Storage and Handling 
All study drugs will be shipped from the Sponsor or Sponsor resources to the CRU’s pharmacy. 
The study medication must be carefully maintained at 25°C; excursions permitted to 15-30°C.  
The CRU’s pharmacy will maintain an inventory record of the IPs received, stored (in a secure 
restricted area), and dispensed. IPs will be provided to study subjects only. 
 Method of Assigning Subjects to Treatment Groups 
The CRU will generate the randomization code for each cohort with a computer program 
according to the study design, the number of subjects and the treatment to be administered. Once 
generated, the randomization code will be final and will not be modified. 
Subjects enrolled in the SAD sentinel groups will be randomized 1:1 to receive SBP-9330 or 
matching placebo while the rest of the subjects in the cohort will be randomized 5:1 to receive 
SBP-9330 or matching placebo. Subjects enrolled in the MAD and Smoker cohorts will be 
randomized 8:2 to receive SBP-9330 or matching placebo. 
Subjects who sign the informed consent form (ICF) and are randomized but do not receive the 
study treatment may be replaced. Subjects who sign the ICF, are randomized and received at 
least 1 dose of the study treatment, and are withdrawn prematurely from the study, may be 
replaced by an equal number of newly enrolled subjects. A new unique randomization number 


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will be assigned to the replacement subject. The replacement list will be provided and will be 
identical to the original randomization scheme. 
 Blinding 
This study is double-blind. Treatment assignments (active or placebo) will be blinded to the 
investigator, subjects and all clinical and research staff for the entire study, with the exception of 
designated pharmacy staff who will remain unblinded in order to dispense active drug or 
placebo.  
The study blind will be broken upon completion of the clinical study and after the study database 
has been locked.  
During the study, the randomization code must not be broken except in emergency situations 
where the identification of a subject’s study treatment is required by the qualified investigator for 
further treatment to the subject, to assess cohort stopping rules or to complete a SAE report. 
Randomization information will be held by designated individual(s). When possible, the 
qualified investigator should discuss the emergency with the Sponsor prior to unblinding. The 
date and reason for breaking the blind must be recorded.  
The results of the blinded safety and available PK data will be made available to the DSMB 
group before proceeding with the next dose level. The DSMB will be provided the 
randomization code to aide in the review for Part C. The bioanalytical facility will preserve the 
blind by reassigning alternative subject numbers to the interim data before they are made 
available to the PK facility and Sponsor; these alternative subject numbers will be assigned by 
the lab at the time of sample analysis. For the food-effect cohort (Cohort A3), the clinic will 
provide the lab with the meal condition for each subject, and the lab will translate this 
information to the corresponding alternative subject number and will provide the resulting list 
comprised of alternative number and associated meal condition to the PK scientist. These 
measures will ensure that whenever possible, the DSMB members remain blinded during their 
reviews and throughout the clinical part of the study. Based on review of the safety data, the 
DSMB may request randomization information, if necessary, to make appropriate dose 
escalation decisions and this unblinding will be documented.  
At the request of the Sponsor, specified individuals may be unblinded and receive the 
randomization information prior to database lock. This unblinding will be fully documented and 
all unblinded individuals advised that they must not distribute randomization information to any 
blinded parties. 
 Study Drug Accountability 
Complete and accurate inventory records of all study drugs will be maintained. This includes 
acknowledgment of receipt of each shipment of study product (quantity and condition), subject 
dispensing records, and returned or destroyed study product. 
The labeling, storage conditions, quantity of reserve samples for the IP, and retention period of 
the reserve samples shall comply with the current FDA rules and regulations. Drug 
accountability will be performed at the completion of the trial. 


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Administration of Study Drug 
Study drug will be administered in the morning at approximately the same time each day. The 
date and time of each dose will be recorded. For each subject, all scheduled post-dose activities 
and assessments will be performed relative to the time of study drug administration. 
Each oral dose of the assigned formulation will be administered to subjects with approximately 
240 mL of water at ambient temperature. An additional volume of water of up to 150 mL may be 
provided in 50 mL increments to ensure that the whole dose is administered. 
 Part A – SAD phase with Nested Food-Effect Cohort 
For Cohorts A1, A2, A4, and A5, dosing will occur following a minimum 10-hour overnight fast. 
Fasting will continue for at least 4 hours following drug administration, after which a 
standardized lunch will be served.  
For Cohort A3 only, during Period 1, dosing will occur following a minimum 10-hour overnight 
fast. Fasting will continue for at least 4 hours following drug administration, after which a 
standardized lunch will be served. During Period 2, dosing will occur following a minimum 
10-hour overnight fast and 30 minutes after the start of a high-fat, high-calorie breakfast. An 
example meal would consist of 2 eggs fried in butter, 2 strips of bacon, 2 slices of toast with 
butter, 4 ounces of hash brown potatoes and 8 ounces of whole milk. Substitutions in this test 
meal may be made provided that the meal delivers a similar number of calories from protein, 
carbohydrate, and fat and has comparable meal volume and texture. Subjects must eat the total 
content of this meal in 30 minutes or less. A standardized lunch will be served at least 4 hours 
after dosing.  
Water will be provided as needed until at least 1 hour pre-dose. Water will be allowed beginning 
at least 1 hour after the administration of the drug. 
 Parts B and C – MAD and Smoker Phase 
From Days 1 to 14, dosing will occur following a minimum 10-hour overnight fast. 
On Days 1 and 14 only, fasting will continue for at least 4 hours following drug administration, 
after which a standardized lunch will be served. Water will be provided as needed until at least 1 
hour pre-dose. Water will be allowed beginning at least 1 hour after the administration of the 
drug. 
Meals and water will be provided at least 1-hour postdose on Days 2 to 13.  
 Treatment Compliance 
The study drug will be dispensed only to eligible subjects and administered under the supervision 
of study personnel. Treatment compliance will be verified according to the site’s standard 
operating procedures (SOPs). 
 
Meals and Fluids 
Food and fluid intake other than water will be controlled for each confinement period and for all 
subjects. Meals and fluids will be provided at appropriate times during the confinement periods 
unless otherwise specified in this protocol. 


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Other Protocol Restrictions 
 Part A – SAD phase with Nested Food-Effect Cohort 
Subjects will remain seated or kept in minimal ambulatory movement for the first 4 hours 
following drug administration. However, should AEs occur at any time, subjects may be placed 
in an appropriate position. Subjects will not engage in strenuous activity at any time during the 
confinement periods. 
 Parts B and C– MAD and Smoker Phase 
On Day 1, subjects will remain seated or kept in minimal ambulatory movement for the first 
4 hours following drug administration. On Days 2 to 14, subjects will remain seated or kept in 
minimal ambulatory movement for the first hour following drug administration. However, 
should AEs occur at any time, subjects may be placed in an appropriate position. Subjects will 
not engage in strenuous activity at any time during the confinement periods. 


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6. 
STUDY PROCEDURES 
Unless otherwise stated in the protocol, the SOPs of the study facilities, which are available for 
all activities relevant to the quality of the study, will be followed during this study. Procedure 
windows, including PK sample collection windows, will follow the CRU’s SOPs. 
An overview of the study activities for each participant is detailed in Table 1 (SAD Phase), 
Table 2 (MAD Phase), or Table 3 (Smoker Phase). 
When safety, PK blood draws, and/or smoking assessments coincide, procedures should be 
carried out in the following order: (1) ECGs, (2) vital signs, (3) PK blood sampling (nominal), 
(4) smoking assessments. 
Any deviation from protocol procedures should be noted in the source documentation and 
compiled for reporting in the Clinical Study Report. 
 
Safety Assessments 
Safety assessments will include physical examination, vital signs, 12-lead ECG, clinical 
laboratory tests, C-SSRS, and AE monitoring. At the discretion of an Investigator, additional 
safety assessments may be performed as needed to ensure subject safety. 
Subjects will be admitted to the CRU, where they will be monitored to detect AEs during the 
study and followed appropriately to ensure resolution of AEs. An Investigator in charge will be 
present at the CRU for at least the first 4 hours following drug administration (on Day 1 only for 
the MAD Phase) and will remain available at all times throughout the study. An Advanced 
Cardiovascular Life Support (ACLS)-certified Safety Officer/Paramedic will be onsite 24/7, to 
assist Investigators with any observed AEs and the medical management of study participants. 
Adverse events, such as but not limited to syncope and seizures, will be managed according to 
standard of care. A crash cart will be available in the CRU. 
 Medical History 
The medical history at Screening will include all queries by the medical and clinical staff related 
to the subject’s well-being and history of relevant past medical events/experiences. Medical 
history will include all demographic data (age, sex, race, body weight, height, and BMI) and 
baseline characteristics. Alcohol and smoking habits will also be recorded. 
Smoking history will also be collected at Screening for Part C. 
 Physical Examination 
A physical examination will be performed by a medically qualified and licensed individual as 
outlined in Table 1 (SAD Phase), Table 2 (MAD Phase) or Table 3 (Smoker Phase). 
The physical examination will include a general review of the following body systems (at 
minimum): general appearance, head, eye, ear, nose, throat, neck/thyroid, cardiovascular, 
respiratory, gastrointestinal, neurological, musculoskeletal/extremities, and skin. An abbreviated 
physical examination may be performed at the Investigator’s discretion upon admission or 
discharge from the clinical site. 


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 Vital Signs 
Vital signs will be measured as outlined in Table 1 (SAD Phase), Table 2 (MAD Phase) or 
Table 3 (Smoker Phase). 
Vital signs to be measured are listed below. 
• Orthostatic systolic and diastolic BP and pulse rate 
• Body temperature 
• Respiratory rate 
Blood pressure and pulse rate will be measured after the subject has been in the supine position 
for at least 5 minutes, repeat measurements will be taken after the subject has been standing in 
the upright position for at least 2 to 3 minutes (respiratory rate and temperature will be measured 
with blood pressure and pulse rate in the supine position only).  
When vital signs are scheduled at the same time as PK blood draws, the blood draws will be 
obtained at the scheduled time point and the vital signs will be obtained prior to the blood draw, 
as close as possible to the scheduled time point.  
On-study time points for vital sign measurements are presented in Table 10 (SAD Phase) and 
Table 11 (MAD and Smoker Phase). 
Table 10 Vital Sign Recording Schedule – SAD Phase 
Vital Sign Recording - Scheduled Time Points1 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) 
0.75, 1.25, 1.75, 3.75, 8, 11.75, and 23.25 hours post-dose (±15 minutes) 
Prior to discharge  
End of Study/Follow-up Visit 
1For the food-effect cohort, the vital signs assessments will be performed for each dosing 


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Table 11 Vital Sign Recording Schedule – MAD and Smoker Phase 
Vital Sign Recording - Scheduled Time Points 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) 
1.75 hours post-dose (±15 minutes) on each dosing day  
3.5 hours post-dose (±15 minutes) on each dosing day1  
Prior to discharge 
End of Study/Follow-up Visit 
1. 
Time point applicable to Smoker Phase only. 
The normal range values for vital signs are as follows:  
• 100 mmHg ≤ systolic blood pressure (BP) ≤ 140 mmHg in supine position. 
• 60 mmHg ≤ diastolic BP ≤ 90 mmHg in supine position. 
• 60 beats per minute (bpm) ≤ heart rate ≤ 100 bpm in supine position. 
• 35.5 °C ≤ body temperature ≤ 37.5 °C. 
• 10 breaths per minute ≤ respiratory rate ≤ 22 breaths per minute. 
•  ≥ 20 mmHg decrease in systolic BP from supine to standing. 
• ≥ 10 mmHg decrease in diastolic BP from supine to standing. 
• ≥ 30 bpm increase in heart rate from supine to standing. 
 12-Lead Electrocardiogram 
Triplicate 12-lead ECG (each performed approximately 1 minute apart) will be performed as 
outlined in Table 1 (SAD Phase), Table 2 (MAD Phase) or Table 3 (Smoker Phase). 
On-study ECG measurements are specified in Table 12 (SAD Phase) and Table 13 (MAD and 
Smoker Phase). 


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Table 12 ECG Recording Schedule – SAD Phase 
ECG Recording - Scheduled Time Points1 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) 
1, 3, 6, and 12 hours post-dose (±15 minutes) 
Prior to discharge  
End of Study/Follow-up Visit 
1For the food-effect cohort, the vital signs assessments will be performed for each dosing 
Table 13 ECG Recording Schedule – MAD and Smoker Phase 
ECG Recording - Scheduled Time Point 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) on Day 1 only 
3 hours post-dose (±15 minutes) on each dosing day  
Prior to discharge 
End of Study/Follow-up Visit 
 Laboratory Evaluations 
Laboratory evaluations will be performed as outlined in Table 1 (SAD Phase), Table 2 
(MAD Phase), or Table 3 (Smoker Phase). 
The laboratory evaluations to be conducted for this study are presented in APPENDIX 6. 
Additional clinical laboratory tests may be performed by the medical laboratory as part of larger 
standard test panels (not required for subject safety). 
An Investigator in charge or delegate will assess each abnormal value to determine if it is 
clinically significant. Post-dose clinically significant laboratory values will be reported as AEs, if 
applicable, as judged by an Investigator or delegate. 
Only test results required by the protocol and/or abnormal results will be entered in the clinical 
database and reported in the Clinical Study Report, based on report requirement. 
 Columbia Suicide Severity Rating Scale (C-SSRS) 
The C-SSRS is a questionnaire designed for the assessment of suicidal ideation and behavior in 
adolescents and adults. This will include events in the last 2 years prior to Screening.  
To monitor for the emergence of suicidal ideation and behavior, subjects will undergo C-SSRS 
evaluations at the time points indicated in Table 1 (SAD Phase), Table 2 (MAD Phase), or 
Table 3 (Smoker Phase). 
The questionnaire must be administered by an Investigator or other individual that is suitably 
qualified by education or training. See APPENDIX 7 for a sample C-SSRS (Baseline/Screening 


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Version) assessment and APPENDIX 8 for a sample post-dose C-SSRS (Since Last Visit 
Version) assessment. The Baseline/Screening Version of the C-SSRS will be used at Screening 
and a Since Last Visit Version will be used at all subsequent visits where the C-SSRS is 
administered. 
On-study C-SSRS should be completed upon admission, upon discharge (each admission and 
discharge for Cohort A3 [Food-Effect Cohort]) and the EOS/Follow-up visit. 
If a subject becomes suicidal during the study as per the results of the C-SSRS questionnaire, an 
Investigator should provide the appropriate treatment to the subject. 
 Mini International Neuropsychiatric Interview (M.I.N.I.) 
The M.I.N.I. is a clinician-rated diagnostic assessment that will be administered at Screening and 
will be considered a source document31. The M.I.N.I will be administered by an Investigator or 
other individual that is suitably qualified by education or training. See APPENDIX 9 for a 
sample M.I.N.I. assessment.  
 
Blood Volume Collected 
The total volume of blood withdrawn, including the volume required for screening, on-study and 
post-study tests, should be approximately: 
• 166 mL for Part A – SAD Phase (Cohorts A1, A2, A4, and A5) 
• 250 mL for Part A – SAD Phase (Cohorts A3 [Food-Effect Cohort]) 
• 330 mL for Part B – MAD Phase (all cohorts) 
• 379 ml for Part C – Smoker Phase (all cohorts) 
The total blood donation may be higher if repeat blood samples are required for safety assessments. 
 
Pharmacokinetic Assessments 
Blood samples will be collected (1 tube of 6 mL each) for PK assessments. 
For the SAD Phase, blood sampling for PK of SBP-9330 in plasma will be performed at pre-dose 
(within 60 minutes of dosing) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 48 hours post-
dose (±10%). The food-effect cohort will have identical PK draws in Periods 1 and 2. 
For the MAD and Smoker Phase, blood sampling for PK of SBP-9330 in plasma will be done at 
the following timepoints: 
• At pre-dose (within 60 minutes of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 
24 hours post-dose (±10%) on Day 1 
• At predose (within 60 minutes prior to morning drug administration) on Day 7, 11, 12, 
and 13 
• At pre-dose (within 60 minutes prior to drug administration) and at 0.25, 0.5, 1, 1.5, 2, 3, 
4, 6, 9, 12, 24, 36, and 48 hours post-dose on Day 14 (±10%). 


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The complete blood sampling schedule is also presented Table 1 (SAD Phase), Table 2 (MAD 
Phase) or Table 3 (Smoker Phase). 
Blood samples will be collected by direct venipuncture into a labeled tube containing the 
appropriate anticoagulant as specified by the bioanalytical facility. As an option to the subject or 
if judged necessary by the clinical staff, blood samples may be collected from an indwelling 
cannula (stylet catheter that requires no flushing), which will be placed in the vein of the subject. 
The time of PK blood sample collection will be calculated relative to the time of treatment 
administration. The actual time of all PK blood draws will be recorded and reported for all 
subjects. 
SBP-9330 concentrations for PK assessments will be obtained through bioanalysis of the plasma 
derived from the blood samples drawn during this study, using a validated bioanalytical method. 
Bioanalysis procedures will be presented in the bioanalytical plan. 
 Pharmacokinetic Sample Processing, Storage and Shipping 
Blood samples for PK determination will be processed, stored, and shipped according to the 
sample processing instructions supplied by the bioanalytical facility.  
 Residual Biological Samples 
Plasma samples remaining after the completion of protocol-defined analyses will be retained for 
potential future metabolite and/or biomarker analysis. No characterization of human genetic 
material (genes, DNA, RNA) will be performed.  
 
Smoking Assessments for Part C only 
 Fagerström Test for Cigarette Dependence (FTCD) 
The Fagerström Test for Cigarette Dependence (FTCD) is a standardized self-report 
questionnaire measuring nicotine dependence severity administered at Screening and will be 
considered a source document. The FTCD will be administered by an Investigator or other 
individual that is suitably qualified by education or training. See APPENDIX 10 for a sample 
FTCD. 
 Smoking Time-Line Follow-back (TLFB) 
The Smoking Time-Line Follow-back (TLFB) is a standardized method to obtain estimates of 
daily consumption of tobacco cigarettes using a calendar technique administered at Screening 
and on Day -1 and will be considered a source document. The Smoking TLFB will be 
administered by an Investigator or other individual that is suitably qualified by education or 
training.  


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 Expired Carbon Monoxide (ECO) Level 
Expired breath CO will be measured with a Bedfont Smokerlyzer™ at the following timepoints 
as outlined in Table 3: 
• Screening 
• Check-in (Day -1) 
• At predose on Days 1 to 14 
 Blood Sampling for Cotinine 
Blood samples will be collected (1 tube of 3 mL each) to measure plasma cotinine levels at 
predose on Days 1, Day 7, and Day 14 as outlined in Table 3. 
Blood samples will be collected by direct venipuncture into a labeled tube containing the 
appropriate anticoagulant as specified by the bioanalytical facility. As an option to the subject or 
if judged necessary by the clinical staff, blood samples may be collected from an indwelling 
cannula (stylet catheter that requires no flushing), which will be placed in the vein of the subject. 
Cotinine concentrations for smoking assessments will be obtained through bioanalysis of the 
plasma derived from the blood samples drawn during this study, using a validated bioanalytical 
method. 
Bioanalysis procedures will be presented in the bioanalytical plan. 
 Smoking Log  
Subjects will be asked to provide sufficient quantity of their usual brand of cigarettes to smoke 
during their confinement. Subjects will ask for a cigarette from the clinical staff each time they 
want to smoke. A daily smoking log will be kept to document the number of cigarettes smoked 
by the subjects from Day -1 to Day 15 as outlined in Table 3.  
 Minnesota Nicotine Withdrawal Scale (MNWS) 
The Minnesota Nicotine Withdrawal Scale (MNWS) is a self-report measure used to monitor 
symptoms of tobacco withdrawal. The MNWS will be administered by an Investigator or other 
individual that is suitably qualified by education or training on Day -1 and at 5 hours 
(±30 minutes) postdose on Days 1 to 14 as outlined in Table 3. The assessment on Day -1 should 
be completed at approximately the same time as the 5-hour postdose timepoint on dosing days. 
See APPENDIX 11 for a MNWS example. 
 Questionnaire on Smoking Urges – Brief version (QSU-Brief) 
The Questionnaire on Smoking Urges – Brief version (QSU-Brief) is a self-report questionnaire 
used to measure cravings to smoke. The QSU-Brief will be administered by an Investigator or 
other individual that is suitably qualified by education or training on Day -1 and at 5 hours 
(±30 minutes) postdose on Days 1 to 14 as outlined in Table 3. The assessment on Day -1 should 
be completed at approximately the same time as the 5-hour postdose timepoint on dosing days. 
See APPENDIX 12 for a QSU-Brief example. 


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7. 
ADVERSE EVENTS DOCUMENTATION 
 
Definitions 
An AE is defined as any untoward medical occurrence in a subject administered an 
investigational product and which does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavorable and unintended sign (including for example, 
a clinically significant abnormal clinical laboratory finding), symptom, or disease temporally 
associated with the use of an investigational product, whether or not related to the investigational 
product. 
A suspected adverse reaction (SAR) is any AE for which there is a reasonable possibility the 
drug caused the AE. ‘Reasonable possibility’ means there is evidence to suggest a causal 
relationship between the drug and the AE. A suspected adverse reaction implies a lower degree 
of certainty about causality than adverse reaction, which means any AE caused by a drug. 
An AE may be: 
• A new illness, 
• Worsening of a concomitant illness, 
• An effect of the study drug including comparator; it could be an abnormal clinical 
laboratory value as well as a significant shift from baseline within normal range which an 
investigator considers to be clinically important. 
Surgical procedures themselves are not AEs. They are therapeutic measures for conditions that 
required surgery. The condition for which the surgery is required is an AE, if it occurs or is 
detected during the study period. Planned surgical measures permitted by the clinical study 
protocol and the conditions(s) leading to these measures are not AEs, if the condition(s) was 
(were) known before the start of study treatment. In the latter case, the condition should be 
reported as medical history. 
A Serious Adverse Event (SAE) or reaction is any untoward medical occurrence that at any dose: 
• Results in death, 
• Is life-threatening, 
• Requires inpatient hospitalization or prolongation of existing hospitalization, 
• Results in persistent or significant disability or incapacity (defined as a substantial 
disruption of a person’s ability to conduct normal life functions), 
• Is a congenital anomaly or birth defect, 
• Is an important medical event that may jeopardize the subject or may require intervention 
to prevent one of the other outcomes listed above (according to medical judgment of an 
investigator) 
 
Severity Assessment 
All AEs will be graded as mild, moderate, or severe according to the following definitions: 


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Mild:  
Causing no limitation of usual activities; the subject may experience transient slight 
discomfort 
Moderate:  Causing some limitation of usual activities; the subject may experience annoying 
discomfort 
Severe:  
Causing inability to carry out usual activities; the subject may experience intolerable 
discomfort or pain 
Every effort will be made to obtain an adequate evaluation of the severity. 
 
Causality Assessment 
An Investigator will determine the relationship of any AE to the study drug using the guidelines 
presented in Table 14. 
Table 14 Adverse Event Relationship to Study Drug 
Relationship to Drug 
Comment 
Definite 
A clinical event, including laboratory test abnormality, occurring in a 
plausible time relationship to drug administration and which cannot be 
explained by concurrent disease or other drugs or chemicals. The 
response to withdrawal of the drug (de-challenge) should be clinically 
plausible. The event must be definitive pharmacologically or 
phenomenologically using a satisfactory rechallenge (the drug is 
readministered to determine if the same reaction occurs) procedure if 
necessary. 
Probable 
A clinical event, including laboratory test abnormality, occurring in a 
plausible time relationship to drug administration and which cannot be 
explained by concurrent disease or other drugs or chemicals. The 
response to withdrawal of the drug (de-challenge) should be clinically 
plausible. 
Possible 
A clinical event, including laboratory test abnormality, with a 
reasonable time sequence to the drug administration, but which could 
also be explained by concurrent disease or other drugs or chemicals. 
Information on drug withdrawal may be lacking or unclear. 
Unlikely 
A clinical event, including laboratory test abnormality, with a 
temporal relationship to drug administration which makes a causal 
relationship improbable and in which other drugs, chemicals or 
underlying disease provide plausible explanations. 
Not related 
Any event that does not meet the above criteria; there is sufficient 
information that etiology of the event is in no relation to the study 
drug. 
 
Adverse Event Monitoring 
For the purposes of this study, the monitoring period for AEs extends from the pretrial evaluation 
until the Follow-up Visit. From Screening to the first dose of the study, AEs will be recorded as 
screening events or as part of the medical history, as applicable. AEs occurring after initiation of 
study drug will be indicated as TEAEs in the clinical study report. 


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Subjects will be questioned on their health status at the beginning of each study period and 
before each departure from the CRU. Open-ended questions will be asked. 
During the study, all AEs spontaneously reported by the subject, observed by the clinical staff or 
elicited by general questioning will be recorded for all subjects and reported in the CRF. 
If necessary, every effort will be made to obtain an adequate follow-up of the subjects. Should 
any subject choose to withdraw from the study, they will be advised of the safety precautions to 
be taken. 
Any AE which remains unresolved as of the last visit will require an evaluation and follow-up 
until the AE has been resolved or a reasonable explanation for its persistence found, or is deemed 
mild and safely resolving. 
In the case of AEs deemed related to the Investigational Product, every effort will be made to 
determine the final outcome. 
It is an investigator’s responsibility to ensure that subjects experiencing AEs receive appropriate 
follow-up treatment where required, and that every action is well documented. 
Classification of AEs will be performed by System Organ Class (SOC) and Preferred Term (PT) 
using the Medical Dictionary for Regulatory Activities (MedDRA), version 23.0 or higher. 
Concomitant medications will be coded using the World Health Organization drug dictionary 
(WHO-DDE March 2019 or later). 
 
Reporting of Pregnancy 
Pregnancy in a female study subject shall be reported to the Sponsor within 24 hours of the 
knowledge of its occurrence by an investigator or delegate (for pregnancies occurring during the 
course of the study or immediately following the end of the study). Because of the possibility the 
fetus/embryo could have been exposed to the study drug through the parent and for the subject’s 
safety, the pregnancy will be followed up to determine its outcome, including spontaneous or 
voluntary termination, details of birth, presence or absence of any birth defects, congenital 
anomalies, or maternal and/or newborn complications. 
Pregnancy that occurs within 4 weeks after the last drug administration in a female partner of a 
male study subject shall be reported to the Sponsor within 24 hours of the knowledge of its 
occurrence by the clinical site that such pregnancy occurred during the course of the study or 
right after. Because of the possibility that the fetus/embryo could have been exposed to the study 
drug through the parent and for the safety of the subject’s female partner, the pregnancy will be 
followed up to determine its outcome, including spontaneous or voluntary termination, details of 
birth, presence or absence of any birth defects, congenital anomalies, or maternal and/or newborn 
complications. 
The pregnancy will be recorded and reported by the CRU to the Sponsor. Pregnancy follow-up 
will also be properly recorded to ensure quality and completeness of the data belonging to the 
study drug and will include an assessment of the possible causal relation between the study drug 
and any pregnancy outcome. Any SAE experienced during pregnancy will be reported on an 
SAE Report Form. 


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Serious Adverse Event Reporting 
The CRU will notify any SAE to the Sponsor, without regard to causality, within 24 hours after 
becoming aware of its occurrence. The NIDA Project Official (Tanya Ramey, MD PhD) and 
Project Scientist (Evan Herrmann, PhD) will be notified of the SAE within 72 hours of the SAE 
occurrence via email. 
If, during follow-up, any non-serious AE worsens and eventually meets the criteria for an SAE, 
that AE should be recorded as a new SAE. 
The initial SAE report must be as complete as possible, including details of the current illness 
and SAE, and an assessment of the causal relationship between the event and the investigational 
product(s). Information not available at the time of the initial report (e.g., an end date for the AE, 
laboratory values received after the report, or hospital discharge summary) must be documented. 
All follow-up information must be reported as soon as the relevant info is available. 
The notification should be directed to the following Sponsor representative: 
Vijay Hingorani, MD, PhD 
Study Medical Monitor 
Tel.: (858) 864-8124 
Email: vhingorani@vh-inc.com 
An SAE will be considered “unexpected” if the AE is not listed in the investigator brochure or is 
not listed at the specificity or severity that has been observed; or, if an investigator brochure is 
not required or available, is not consistent with the risk information described in the general 
investigational plan or elsewhere in the current application. "Unexpected," as used in this 
definition, also refers to AEs that are mentioned in the investigator brochure as occurring with a 
class of drugs or as anticipated from the pharmacological properties of the drug but are not 
specifically mentioned as occurring with the particular drug under investigation. 
All serious, unexpected, related AEs must be reported to the IRB. The event will be reported via 
fax or email within 15 calendar days of an investigator or staff becoming aware of the event. 
The Sponsor will determine whether the SAE must be reported in an expedited manner to the 
applicable regulatory agencies. If so, the Sponsor will report the event to those agencies and to 
all participating investigators. 
If reports of any new and unexpected AEs become available to the Sponsor during the clinical 
portion of this study (related or not to the present study), the Sponsor must advise the CRU, 
through its clinical investigator, of those events. If required by the Sponsor, the CRU may advise 
the applicable regulatory authorities. 
 Drug-Induced Liver Injury 
Abnormal values in aspartate transaminase (AST) and/or alanine transaminase (ALT) concurrent 
with abnormal elevations in total bilirubin that meet the criteria outlined below in the absence of 
other causes of liver injury are considered potential cases of drug-induced liver injury (potential 
Hy’s Law cases) and should always be considered important medical events. 


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Subjects with AST or ALT and total bilirubin baseline values within the normal range who 
subsequently present with AST or ALT  3 times the upper limit of normal (3X ULN) 
concurrent with a total bilirubin  2 X ULN with no evidence of hemolysis and an alkaline 
phosphatase  2 X ULN or not available, with no other cause for LFT abnormalities identified at 
the time should be considered to have potentially met Hy’s Law. Such potential Hy’s Law cases 
should be reported as SAEs. 


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8. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
 
Analysis Populations 
 Safety Population 
The Safety population will include all subjects who received at least 1 dose of either the SBP-
9330 or placebo. 
The number of subjects who were included, who discontinued, and who completed the study will 
be tabulated. The primary reasons for discontinuation will be provided. 
 Pharmacokinetic Population 
The PK population will include all subjects who have received at least 1 dose of SBP-9330 and 
have at least 1 PK concentration after dosing will be included in the PK population. 
The PK population will be described in a Statistical Analysis Plan (SAP). 
 
Demographic Data and Other Baseline Characteristics 
Listings and descriptive summary statistics of demographic (age, sex, race, height, body weight 
and BMI) and baseline data will be presented. 
Statistics for demographic and baseline data will be further detailed in the SAP. 
 
Safety 
 Safety Endpoints 
The primary safety endpoint includes the incidence of subjects who experienced an AE and 
severity of AEs following study drug administration. Changes in vital signs, physical 
examination findings, 12-lead ECG findings, C-SSRS questionnaire findings, and clinical 
laboratory abnormalities will also be assessed. 
 Safety Analysis 
Reported AEs, results from clinical laboratory tests, vital signs measurements, ECGs, physical 
examinations, C-SSRS questionnaires and other safety parameters will be used to perform the 
safety statistical analysis. 
 Safety Statistical Methodology 
Descriptive statistics will be used to summarize AEs and safety results. 
 Pharmacokinetics 
The PK analysis will be carried out according to Altasciences SOPs. Pharmacokinetic data 
handling and analysis will also be detailed in the SAP. 
 Missing Values 
The lack of concentration values due to failure to collect the sample, a lost or compromised 
sample or due to the subject’s early termination from the study will be considered “missing” in 
the dataset, and no imputation will be done. 
If the actual collection time of a post-dose PK sample is unknown, but a valid concentration 
value has been measured, the sample will be set to missing in the PK analysis and will be 


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presented in the listings as excluded from descriptive statistics. Unknown pre-dose collection 
times will be handled on a case-by-case basis. 
 Measurements Below the Lower Limit of Quantitation 
Concentration values below the lower limit of quantitation (LLOQ) associated with pre-dose and 
post-dose collection times will be replaced with zero for the non-compartmental analyses (NCA); 
additional rules for samples that are below the LLOQ, if applicable, will be detailed in the SAP. 
Concentration values below the LLOQ will be replaced with zero for mean PK profile 
representations as well as for descriptive statistic calculations. 
 Actual Time 
The NCA analysis will be based on the actual sampling times, except for predose samples, which 
will always be reported as zero, regardless of time deviations, provided that they were collected 
prior to dosing. 
The individual concentration/time profiles will be presented using actual sampling times whereas 
the mean concentration/time profiles and tables presenting summary statistics of concentration 
time data will be presented using nominal sampling times. 
Actual times will be listed in the report. 
 Baseline Reference Timepoint 
Unless otherwise specified, the baseline value will be defined as the last non-missing evaluation 
prior to the first drug administration. 
 Non-Compartmental Analysis 
The following configuration for the NCA analysis (with Phoenix® WinNonlin® version 8, or 
higher) will be used: 
• Data: 
Serial sampled data 
• Model/Dose options Type:  Plasma (200 -202) / Extravascular 
• AUC Calculation Method: 
Linear Up Log Down 
• Lambda Z (λz) calculation: 
Best fit method for λz Linear-Log regression 
Reasons for excluding PK parameters will include the following: 
• AUC: AUC parameters will not be estimated if less than 3 consecutive measurable 
concentrations are observed. 
• PK parameters requiring λz estimation (e.g., AUC0-∞ and Thalf) will be set to Not 
Reported (NR) in the Tables and Listings if they meet one of the following: 
▪ R2 < 0.8  
▪ Extrapolated area > 20%  
▪ 3 time points used for terminal phase estimation include Cmax 
The PK parameters for SBP-9330 in plasma are presented in Table 15. 


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Table 15 Pharmacokinetic Parameters of SBP-9330 in Plasma 
PK Parameter 
Definition 
Part A: SAD Phase 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration 
AUC0-24 
Area under the concentration time curve from time 0 (dose administration) to 
24 hours 
AUC0-T 
Area under the concentration time curve from time 0 (dose administration) to 
the time of last quantifiable concentration (Tlast) 
AUC0-∞ 
Area under the concentration time curve extrapolated to infinity, calculated as 
AUC0-T + Clast/λZ, where Clast is the measured concentration at time Tlast 
Thalf 
Terminal elimination half-life, calculated as ln(2)/λZ 
CL/F 
Apparent total clearance, calculated as Dose/AUC0-∞ 
Vz/F 
Apparent volume of distribution, calculated as Dose/λZ * AUC0-∞ 
Cmax/D 
Dose-normalized Cmax 
AUC0-T/D 
Dose-normalized AUC0-T 
AUC0-∞/D 
Dose-normalized AUC0-∞ 
Part B: MAD Phase, Day 1: 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration 
AUC0-24 
Area under the concentration time curve from time 0 (dose administration) to 
24 hours 
AUC0-T 
Area under the concentration time curve from time 0 (dose administration) to 
the time of last quantifiable concentration (Tlast) 


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Part B and Part C: MAD and Smoker Phase, Day 14: 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration; if it occurs at more than one time 
point, Tmax is defined as the first time point with this value 
Cτ 
Concentration at the end of the dosing interval. Observed concentration, 
otherwise the predicted concentration value will be calculated as per Phoenix® 
WinNonlin®’s built-in rules for interpolation/extrapolation, and subject to the 
criteria for PK parameters requiring λz estimation. 
AUCτ 
Area under the concentration time curve over the dosing interval at steady state, 
calculated from 0 to 24 hours (dosing interval)  
AUC0-T 
Area under the concentration time curve from time 0 (dose administration) to 
the time of last quantifiable concentration (Tlast) 
Thalf 
Terminal elimination half-life, calculated as ln(2)/λZ 
Thalf, eff 
Effective half-life, calculated as  
τ * ln2 /ln(Rac(AUC)/( Rac(AUC)-1)), where τ is 24 hours1 
CL/Fss 
Apparent total clearance at steady state, calculated as Dose/AUCτ  
Vz/Fss 
Apparent volume of distribution at steady state, calculated as Dose/λZ * AUCτ  
Cmax/D 
Dose-normalized Cmax 
AUCτ/D 
Dose-normalized AUCτ 
AUC0-T/D 
Dose-normalized AUC0-T 
Rac(Cmax) 
Accumulation ratio evaluated by comparing Day 14 Cmax to Day 1 Cmax 
Rac(AUC) 
Accumulation ratio evaluated by comparing Day 14 AUCτ to Day 1 AUC0-24 
Part B and Part C: MAD and Smoker Phase, Various Days: 
Ctrough 
Observed concentration at the end of the dosing interval 
The following PK parameters will be used for PK calculation and presented in the PK listings 
only 
Tlast 
Time of last measurable observed concentration 
Clast 
Observed concentration corresponding to Tlast  
λZ 
Apparent elimination rate constant, estimated by linear regression of the 
terminal linear portion of the log concentration versus time curve 
λZ Upper 
Upper limit on time for values included in the calculation of λz 
λZ Lower 
Lower limit on time for values included in the calculation of λz 
Number of Points 
Number of data points in computing λZ 
R2 
Goodness of fit for the terminal phase 
Residual area  
Extrapolated area (i.e., percentage of AUC0-∞ due to extrapolation from Tlast to 
infinity: AUC0-∞ - AUC0-T/ AUC0-∞*100) 
1.  Sources: Gidal et al., 2017 and Boxenbaum et al., 1995 


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 Data Precision 
Precision for individual values will be display as follows: 
• Raw data will be displayed with the same precision as received from the bioanalytical 
laboratory, 
• Concentration-related PK parameters (e.g., Cmax, AUCs) will be displayed to 3 significant 
figures, 
• Clearance and volume of distribution will be displayed with 3 significant figures, 
• Parameters associated with time will be displayed with 2 decimal places, 
• Percentages will be displayed with 2 decimal places, 
• R2 and λz will be displayed with 4 decimal places. 
 Pharmacokinetic Statistical Methodology 
All tables, figures and listings (TFLs), when appropriate, will be stratified by cohort and study 
day; for the food-effect cohort, additional stratification by meal condition will be performed.  
8.4.7.1. Summary Statistics 
Summary statistics of the individual concentration data and derived parameters will be calculated 
with Phoenix® WinNonlin® for the PK population. Summary statistics will be calculated for 
concentration at each individual time point and for all PK parameters.  
Concentration data will be summarized by group using the following statistics: number of 
observations (N), arithmetic mean (mean), standard deviation (SD), minimum (min), median, 
maximum (max), and coefficient of variation (CV%). PK parameters will be summarized using 
these same statistics, as well as geometric mean and geometric mean CV%. 
Summary statistics will be displayed with the same precision as the individual values 
(Section 8.4.6), with the exception of N and CV% which will be presented with 0 and 1 decimal 
place, respectively. 
8.4.7.2. Statistical Analysis 
Dose Proportionality 
For all study parts, appropriate dose–normalized PK parameters (Cmax and appropriate AUCs) 
will be assessed graphically for dose-proportionality (with Phoenix® WinNonlin®).  
Natural log-transformed PK parameters (Cmax and appropriate AUCs) will be assessed 
statistically for proportionality using SAS. Proportionality analysis will be done using a power 
model. The power model is defined as: 
ln(PK parameter) = α + β • ln(Dose) + ε 
 
where α is the intercept, β is the slope and ε is the error term. A linear model with ln-transformed 
dose as a continuous effect will be fitted. A point estimate and a 90% confidence interval will be 
derived for the slope (β).  


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Dose proportionality may be assessed within different dose ranges if deemed appropriate with at 
least three doses. 
Food-Effect Assessment 
A statistical comparison will be performed in subjects enrolled in Cohort A3 to evaluate the 
effect of food on the PK of SBP-9330 with the natural logarithmic transformation of Cmax, 
AUC0-T, and AUC0-∞.  
Cmax, AUC0-T, and AUC0-∞ will be statistically analyzed using an Analysis of Variance 
(ANOVA) model. The fixed factors included in this model will be the Fed or Fasting condition, 
the period at which it was given (Day 1 or Day 8 [or Day 15]), as well as the sequence in which 
the treatment is under Fed or Fasting condition. A random factor is also added for the subject 
effect (nested within sequence). 
The 90% confidence interval for the exponential of the difference in least-squares (LS) means 
between the Fed and Fasting conditions will be calculated (Fed to Fasting ratio of geometric LS 
means). 
The formula to estimate the intra-subject coefficient of variation will be: 
, where MSE is 
the Mean Square Error obtained from the ANOVA model of the ln-transformed parameters. 
The parameter Tmax will be evaluated descriptively. 
Steady State 
Ctrough will be displayed graphically and summarized descriptively by day to assess for steady 
state. 
 
 Smoking Assessment (Part C only) 
The following data will be assessed for the Safety population of Part C and will be listed and 
summarized using descriptive statistics: 
• Expired carbon monoxide (ECO) level  
• Plasma cotinine level 
• Number of cigarettes smoked (smoking log) 
• 
Minnesota Nicotine Withdrawal Scale (MNWS) responses 
• 
Questionnaire on Smoking Urges – Brief version (QSU-Brief) responses 
Smoking data will be summarized by treatment and dose level using descriptive statistics which 
will be detailed in the SAP. 
 
Planned Interim Pharmacokinetic Analyses 
Interim PK analysis may be performed after each cohort of the SAD, MAD, and Smoker phase 
for dose selection and safety assessment. 
The SAP will describe the planned interim analyses in greater detail. 
1
−
MSE
e


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Determination of Sample Size 
Sample size is based on the estimate of the number of subjects necessary to obtain a clinical 
assessment regarding the drug’s safety profile over the planned dose range and was not based on 
statistical considerations. 


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9. 
REFERENCES 
1. Center for Disease Control and Prevention, Smoking & Tobacco Use, Fast fact Sheet 
https://www.cdc.gov/tobacco/data_statistics/fact_sheets/fast_facts/index.htm#beginning 
2. Garrison GD, Dugan SE. Varenicline: a first-line treatment option for smoking cessation. 
Clin Ther. 2009;31(3):463-91. 
3. McNeil JJ, Piccenna L, Ioannides-Demos LL. Smoking cessation-recent advances. 
Cardiovasc Drugs Ther. 2010;24(4):359-67. 
4. Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet 
Psychiatry. 2016;3(8):760-73. 
5. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th 
ed.) Washington, DC. 2013. 
6. Stolerman IP, Mirza NR, Shoaib M. Nicotine psychopharmacology: addiction, cognition and 
neuroadaptation. Medicinal research reviews. 1995;15(1):47-72.  
7. Substance Abuse and Mental Health Services Administration. Results from the 2009 
National Survey on Drug Use and Health. In: Studies OoA, editor. Bethesda, MD: DHHS; 
2010. 
8. Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nature Reviews 
Neuroscience. 2009;10(8):561-72. 
9. Johnson KA, Lovinger DM. Presynaptic G Protein-Coupled Receptors: Gatekeepers of 
Addiction? Front Cell Neurosci. 2016;10:264 
10. Mansvelder HD, McGehee DS. Long-term potentiation of excitatory inputs to brain reward 
areas by nicotine. Neuron. 2000;27(2):349-57.  
11. D'Souza MS, Liechti ME, Ramirez-Nino AM, Kuczenski R, Markou A. The metabotropic 
glutamate 2/3 receptor agonist LY379268 blocked nicotine-induced increases in nucleus 
accumbens shell dopamine only in the presence of a nicotine-associated context in rats. 
Neuropsychopharmacology : 2011;36(10):2111-24 
12. Koob GF. Neuroadaptive mechanisms of addiction: studies on the extended amygdala. 
European neuropsychopharmacology: 2003;13(6):442-52. 
13. D'Souza MS, Markou A. Differential role of N-methyl-D-aspartate receptor-mediated 
glutamate transmission in the nucleus accumbens shell and core in nicotine seeking in rats. 
Eur J Neurosci. 2014;39(8):1314-22. 
14. Markou A. Metabotropic glutamate receptor antagonists: novel therapeutics for nicotine 
dependence and depression? Biological psychiatry. 2007;61(1):17-22. 
15. Urwyler S. Allosteric modulation of family C G-protein-coupled receptors: from molecular 
insights to therapeutic perspectives. Pharmacol Rev. 2011;63(1):59-126. 
16. Conn PJ, Pin JP. Pharmacology and functions of metabotropic glutamate receptors. Annual 
review of pharmacology and toxicology. 1997;37:205-37. 


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17. Moussawi K, Kalivas PW. Group II metabotropic glutamate receptors (mGlu2/3) in drug 
addiction. European journal of pharmacology. 2010;639(1-3):115-22. 
18. Wright RA, Arnold MB, Wheeler WJ, Ornstein PL, Schoepp DD. [3H]LY341495 binding to 
group II metabotropic glutamate receptors in rat brain. The Journal of pharmacology and 
experimental therapeutics. 2001;298(2):453-60. 
19. Liechti ME, Markou A. Role of the glutamatergic system in nicotine dependence: 
implications for the discovery and development of new pharmacological smoking cessation 
therapies. CNS drugs. 2008;22(9):705-24. 
20. Schwendt M, Reichel CM, See RE. Extinction-dependent alterations in corticostriatal 
mGluR2/3 and mGluR7 receptors following chronic methamphetamine self-administration in 
rats. PloS one. 2012;7(3):e34299 
21. Zhou Z, Karlsson C, Liang T, Xiong W, Kimura M, Tapocik JD, Yuan Q, Barbier E, Feng A, 
Flanigan M, Augier E, Enoch MA, Hodgkinson CA, Shen PH, Lovinger DM, Edenberg HJ, 
Heilig M, Goldman D. Loss of metabotropic glutamate receptor 2 escalates alcohol 
consumption. Proc Natl Acad Sci U S A. 2013;110(42):16963-8. 
22. Wood CM, Nicolas CS, Choi SL, Roman E, Nylander I, Fernandez-Teruel A, Kiianmaa K, 
Bienkowski P, de Jong TR, Colombo G, Chastagnier D, Wafford KA, Collingridge GL, 
Wildt SJ, Conway-Campbell BL, Robinson ES, Lodge D. Prevalence and influence of 
cys407* Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to 
alcohol intake, risk taking and emotional behaviour. Neuropharmacology. 2017;115:128-38. 
23. Semenova S, Markou A. Metabotropic glutamate receptors as targets for the treatment of 
drug and alcohol dependence. In: Skolnick P, editor. Glutamate-based Therapies for 
Psychiatric Disorders. Basel, Switzerland: Springer-Birkhauser; 2010. p. 133-56. 
24. Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, Lu Y, Mansbach RS, 
Mather RJ, Rovetti CC, Sands SB, Schaeffer E, Schulz DW, Tingley FD, 3rd, Williams KE. 
Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist 
varenicline, an effective smoking cessation aid. Neuropharmacology. 2007;52(3):985-94.  
25. Le Foll B, Chakraborty-Chatterjee M, Lev-Ran S, Barnes C, Pushparaj A, Gamaleddin I, Yan 
Y, Khaled M, Goldberg SR. Varenicline decreases nicotine self-administration and cue-
induced reinstatement of nicotine-seeking behaviour in rats when a long pretreatment time is 
used. Int J Neuropsychopharmacol. 2012;15(9):1265-74. 
26. Wouda JA, Riga D, De Vries W, Stegeman M, van Mourik Y, Schetters D, Schoffelmeer 
AN, Pattij T, De Vries TJ. Varenicline attenuates cue-induced relapse to alcohol, but not 
nicotine seeking, while reducing inhibitory response control. Psychopharmacology (Berl). 
2011;216(2):267-77.  
27. George O, Lloyd A, Carroll FI, Damaj MI, Koob GF. Varenicline blocks nicotine intake in 
rats with extended access to nicotine self-administration. Psychopharmacology (Berl). 
2011;213(4):715-22.  
28. O'Connor EC, Parker D, Rollema H, Mead AN. The alpha4beta2 nicotinic acetylcholine-
receptor partial agonist varenicline inhibits both nicotine self-administration following 


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repeated dosing and reinstatement of nicotine seeking in rats. Psychopharmacology (Berl). 
2010;208(3):365-76.  
29. Gidal, B.E., Clark, A.M., Anders, B. and Gilliam, F., 2017. The application of half-life in 
clinical decision making: Comparison of the pharmacokinetics of extended-release 
topiramate (USL255) and immediate-release topiramate. Epilepsy research, 129, pp.26-32. 
30. Boxenbaum, H. and Battle, M., 1995. Effective half‐life in clinical pharmacology. The 
Journal of Clinical Pharmacology, 35(8), pp.763-766. 
31. Sheehan DV, Lecrubier Y, Harnett-Sheehan K, Amorim P, Janavs J, Weiller E, Hergueta T, 
Baker R, Dunbar G: The Mini International Neuropsychiatric Interview (M.I.N.I.): The 
Development and Validation of a Structured Diagnostic Psychiatric Interview. J. Clin 
Psychiatry, 1998;59(suppl 20): 22-33. 
http://www.psychiatrist.com/JCP/article/Pages/1998/v59s20/v59s2005.aspx  


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10. APPENDIX 1: ETHICS 
 Institutional Review Board 
This protocol and the ICF will be submitted to an IRB (or Independent Ethics Committee [IEC]) 
prior to initiation of the study and the study will not start until the Board has approved the 
documents. Notification of the Board’s approval will be appended to the final report. 
 Ethical Conduct of the Study 
This study will be conducted in compliance with the study protocol, the ethical principles that 
have their origins in the Declaration of Helsinki, the International Council for Harmonisation 
(ICH) Guideline E6 for Good Clinical Practice (GCP), the FDA GCP Code of Federal 
Regulations (CFR) Title 21 (part 56), the European regulation EU 536/2014, and the Tri-Council 
Policy Statement (Canada). 
 Subject Information and Consent 
Before screening activities commence, each volunteer will be given a copy of the ICF to read, as 
well as a full explanation of the purpose of the study, the procedures to be carried out, and the 
potential AE(s). Once this essential information is provided to the volunteer and an Investigator 
in charge or delegate has the conviction the volunteer understands the implications of 
participating in the study, and if the volunteer chooses to continue the screening process, they 
will be requested to sign and date a properly executed ICF prior to enrollment. Subjects will be 
assured they may withdraw from the study at any time without jeopardizing their medical care or 
future study participation (for which they qualify). 
Subjects will be given a signed copy of the ICF. If an amended or revised ICF is introduced 
during the study, each subject’s further consent must be obtained. 
 Subject Confidentiality 
Investigators and the Sponsor will preserve the confidentiality of all subjects taking part in the 
study, in accordance with GCP and local regulations. Subjects should be identified by a unique 
subject identifier on all study documents provided to the Sponsor. In compliance with Federal 
regulations/ICH GCP Guidelines, it is required an investigator and institution permit authorized 
representatives of the company, of the regulatory agency(s), and IRB access to review the 
subject’s original medical records for verification of study-related procedures and data. An 
investigator is obligated to inform the subject that his/her study-related records will be reviewed 
by the above named representatives without violating the subject’s confidentiality. 


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11. APPENDIX 2: DATA COLLECTION, RETENTION, AND MONITORING 
 Case Report Forms 
The data required by the protocol is obtained in 2 ways. Source Documents are used in the clinic 
as recording devices during procedures. The data is transcribed from source into an electronic 
data capture (EDC) software (Medrio) and stored in the secure database for each subject included 
in a clinical trial (i.e., who received an IP treatment). Screen Failure data may be transcribed into 
the database at the discretion of the Sponsor. 
Data assembled outside the clinic source will be received from a specified external vendor via an 
electronic data file. The file received encrypted (or posted to a secure File Transfer Protocol) and 
is stored in a secure folder on a server. The electronic data file(s) are independent of the EDC 
data during the conduct of the study. 
The Medrio EDC cleaned data will be reviewed, approved and electronically signed by the 
Principal Investigator or delegate. The Medrio EDC data will be output in a CRF format. The 
external data files will be output in SAS® datasets. All data will be included with the final report 
provided to the Sponsor. 
 Data Management and Processing 
Data Management develops documentation to define activities performed during the data 
management conduct of the study trial. Medrio EDC system is the tool used to conduct all data 
cleaning activities, monitoring activities and review/approval activities for clinic collected data 
and procedure data. The external data files are reconciled (to compare the external vendor data 
and Medrio EDC sample collection data). Data Management activities are performed in 
accordance with the Data Management SOPs. 
In addition to the cleaning activities, data entered in Medrio EDC will be checked for accuracy 
through quality control (QC) assessments. When the database data is declared to be complete and 
accurate, the database will be locked, and user access removed. 
 Quality Control and Quality Assurance 
Designated personnel from the quality assurance unit(s) will be responsible for maintaining QA 
of the clinical, PK, statistical and bioanalytical facilities to ensure that the trial is conducted and 
data are generated, documented and reported in compliance with the protocol, ICH Guideline E6 
for GCP, applicable requirements as outlined in the FDA and OECD Principles of GLP, and the 
Reflection paper for laboratories that perform the analysis or evaluation of clinical trial samples 
(EMA/INS/GCP/532137/2010). 
Designated personnel from each corresponding operation unit will be responsible to maintain and 
assure the QC of all data generated and documented in compliance with the protocol. 
 Record Retention 
All essential documents and records will be maintained by the CRU in accordance with, and for 
the period specified in the applicable regulatory requirement(s) (FDA CFR 312.57 [C]). 


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 Monitoring of the Study 
The Sponsor or its representative may monitor the study at any time in order to maintain current 
and personal knowledge of the study through review of the records, comparison with source 
documents, observation and discussion of the conduct and progress of the study. The CRU will 
permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s) by 
providing direct access to source data/documents. 
 Safety Oversight 
A DSMB will be established and operated according to National Institute on Drug Abuse 
(NIDA) guidelines. The operation of the DSMB will be documented in the Data and Safety 
Monitoring Plan (DSMP) which will be subject to approval by NIDA. The purpose of the DSMB 
is to assure that the safety of study subjects is protected while the scientific goals of the study are 
being met. Specifically, the DSMB is charged with monitoring the safety of participants and the 
quality of the data, as well as the appropriate termination of studies when risks have been 
uncovered or when it appears that the clinical trial cannot be concluded successfully. 


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12. APPENDIX 3: ADMINISTRATIVE PROCEDURES 
 Liabilities 
It is the Sponsor’s responsibility to guarantee sufficient insurance coverage should any serious 
events or deaths result, either directly or indirectly, from the execution of the present protocol. 
 Adherence to Protocol 
Excluding an emergency situation in which proper treatment is required for the protection, safety 
and well-being of the study subjects, the study will be conducted as described in the approved 
protocol and performed according to ICH/GCP and the applicable regulatory requirements. Any 
deviation from the protocol will be recorded and explained. 
If amendments to the protocol and/or amendments or revisions to the ICF are required, the 
modifications will be documented and submitted to an IRB for approval. 
 COVID-19 Response Plan 
Regulatory authorities have recognized that the Coronavirus Disease 2019 (COVID-19) 
pandemic may impact the conduct of clinical trials of medical products. Challenges may arise, 
for example, from quarantines, site closures, travel limitations, interruptions to the supply chain 
for the IP(s), or other considerations if site personnel or study participants become infected with 
COVID-19. These challenges may lead to difficulties in meeting protocol-specified procedures, 
including administering or using the IP or adhering to protocol-mandated visits and 
laboratory/diagnostic testing. To accommodate these challenges and mitigate safety risks 
associated with COVID-19, protocol modifications may be required which include (and are not 
limited to): 
• Conducting the study in multiple (smaller) subject groups; 
• Altering the timing of study procedures and subject confinement; 
• Modification of standard inclusion or exclusion criteria; 
The exact mitigations will be documented in the study Risk Assessment and Mitigation Plan. 
Additional health checks including COVID-19 testing, body temperature monitoring, etc. may be 
performed during the trial, even if not planned within the protocol. 
 Statement of Investigator 
The FDA 1572 form, Statement of Investigator [Title 21, CFR Part 312], will be signed by the 
Investigator, and will be kept on file. 
 Delegation of Investigator Duties 
An investigator will ensure all personnel involved in the trial are adequately qualified and 
informed about the protocol, any amendments to the protocol, the study treatments, and their 
trial-related duties and functions. 
An investigator will maintain a list of sub-investigator(s) and other appropriately-qualified 
persons to whom he/she delegates significant trial-related duties. 


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Should an investigator delegate the supervision of the IP administration to a designated person, 
this individual must have the appropriate professional-legal qualifications and certifications. An 
investigator should also ensure key staff personnel have the appropriate medical qualifications to 
effectively conduct or supervise any potential resuscitation procedures. 
 Premature Termination or Suspension of a Study 
The Sponsor or its representative may terminate the study at any time for scientific or corporate 
reasons. 
If the trial is prematurely terminated or suspended for any reason, the CRU or an Investigator (or 
delegate) should promptly inform the trial subjects, should assure appropriate therapy and 
follow-up for the subjects and should inform the regulatory authority(ies) when required. 


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13. APPENDIX 4: PROTOCOL REVIEW AND APPROVALS 


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TITLE: A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study to Assess 
Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of 
SBP-9330 (with a Nested Food-Effect Arm) after Oral Administration in Healthy Subjects 
 
I have carefully read this study protocol and agree it contains all necessary information required 
to conduct this study. I agree to conduct the study according to this protocol and in accordance 
with GCP and the applicable regulatory requirements. 
___________________________ 
____________________ 
Martin Kankam MD, PhD, MPH 
 
Date (yyyy/mm/dd) 
Principal Investigator 
 


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TITLE: A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study to Assess 
Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of 
SBP-9330 (with a Nested Food-Effect Arm) after Oral Administration in Healthy Subjects 
On behalf of the Sponsor, I am aware of, and agree to comply with, all of the procedures 
contained within this protocol. 
_____________________________ 
____________________ 
Vijay Hingorani, MD PhD 
 
Date (yyyy/mm/dd) 
Study Medical Monitor 
Camino Pharma, LLC  
2022/09/14


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14. APPENDIX 5: LIST OF ABBREVIATIONS 
ACLS 
Advanced Cardiovascular Life Support 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANOVA 
Analysis of Variance 
AST 
Aspartate transaminase 
AUC 
Area under curve 
BCRP 
Breast cancer resistance protein 
BMI 
Body mass index 
BP 
Blood pressure 
bpm 
Beats per minute 
C-SSRS 
Columbia-suicide severity rating scale 
CNS 
Central nervous system 
CO 
Carbon monoxide 
COVID-19 
Coronavirus disease 2019 
CV% 
Coefficient of Variation 
CFR 
Code of Federal Regulations 
CRF 
Case report form 
CRU 
Clinical research unit 
CYP 
Cytochrome P450 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FTCD 
Fagerström Test for Cigarette Dependence 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacture Practice 
h 
Hour 
HBsAg 
Hepatitis B surface antigen 
HCVAb  
Hepatitis C virus antibody 
HED 
Human equivalent dose 


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HIV 
Human immunodeficiency virus 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
iGlu 
Ionotropic glutamate 
IRB 
Institutional Review Board 
IU 
International Unit 
kg 
Kilogram 
L 
Liter 
LLOQ 
Lower limit of quantitation 
LS 
Least-squares 
ln 
Neperian log transformation 
MAD 
Multiple ascending dose 
MedDRA 
Medical dictionary for regulatory activities 
mg 
Milligram 
mGlu 
metabotropic glutamate 
mGlu2 
metabotropic glutamate receptor subtype 2 
mGlu3 
metabotropic glutamate receptor subtype 3 
min 
Minute 
MINI 
Mini International Neuropsychiatric Interview 
mL 
Milliliters 
mmHg 
Millimeter of mercury 
MNWS 
Minnesota Nicotine Withdrawal Scale 
MRSD 
Maximum recommended starting dose 
ms 
millisecond 
MTD 
Maximum tolerated dose 
NAc 
Nucleus accumbens 
NAOEL 
No adverse effect level 
NCA 
Non-compartmental analysis 
NDA 
New Drug Application 
ng 
Nanograms 
NRT 
Nicotine Replacement Therapies 
OECD 
Organization for Economic Co-operation and Development 


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OTC 
Over-the-counter 
p.o. 
Per os 
PAM 
Positive allosteric modulator 
Pgp 
P-glycoprotein 
pH 
The Logarithm, On The Base 10, of The Reciprocal of The Hydrogen Ion 
Concentration 
PK 
Pharmacokinetic 
PT 
Preferred Term 
q.d. 
Once daily 
QA 
Quality Assurance 
QC 
Quality Control 
QSU-Brief 
Questionnaire on Smoking Urges – Brief version 
QTcF 
QT Interval Corrected for Heart Rate using Fridericia's Correction Formula 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System organ class 
SOP 
Standard operating procedure 
TEAE 
Treatment-emergent adverse event 
TLFB 
Time-Line Follow-back 
ULN 
Upper limit of normal 
WHO-DDE 
World Health Organization Drug Dictionary Enhanced  


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15. APPENDIX 6: CLINICAL LABORATORY EVALUATIONS 
Clinical Laboratory Test Panel 
Description 
Clinical Chemistry: 
Alanine aminotransferase, albumin, alkaline phosphatase, bilirubin total, chloride, creatinine, glucose, 
potassium, carbon dioxide, calcium, uric acid, albumin, total bilirubin, lactate dehydrogenase, creatinine 
kinase, aspartate transaminase, amylase, lipase, and sodium 
Lipid profile: 
Total cholesterol, cholesterol high-density lipoprotein, cholesterol low-density lipoprotein and 
triglycerides 
Coagulation: 
Prothrombin time (PT)/INR and partial thromboplastin time (PTT) levels 
Endocrinology1: 
Follicle-stimulating hormone (for female subjects) 
Hematology: 
White cell count with differential (absolute values of neutrophil, lymphocyte, monocyte, eosinophil, and 
basophil), red cell count, hemoglobin, hematocrit, mean corpuscular volume, and platelet count 
Serology1: 
HIV-1/HIV-2 antibodies, hepatitis B surface antigen and hepatitis C virus antibody  
Urinalysis: 
Color, clarity, specific gravity, pH, leukocyte, protein, glucose, ketones, bilirubin, blood, nitrite, 
urobilinogen. Microscopic examination will only be performed if the dipstick test is outside of the 
reference range for leukocyte, blood, nitrite or protein 
Urine drug screen: 
Amphetamines, alcohol, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, opiates and 
phencyclidine 
Pregnancy test: 
Serum pregnancy test at Screening only and urine pregnancy test for all other scheduled days 
 
1 Screening visit only. 


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16. APPENDIX 7: COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) – 
BASELINE/SCREENING VERSION 
 
The Columbia-Suicide Severity Rating Scale Baseline/Screening Version will be provided to the 
clinical site and is not included here in its entirety. 
 


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17. APPENDIX 8: COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) – 
SINCE LAST VISIT VERSION 
The Columbia-Suicide Severity Rating Scale Since Last Visit Version will be provided to the 
clinical site and is not included here in its entirety. 
 
 


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18. APPENDIX 9: MINI INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW 
(M.I.N.I) 
 
The MINI version 7.0.2 will be provided to the clinical site and is not included here in its 
entirety. 
 
M.I.N.I. 
 
MINI INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW 
 
English Version 7.0.2  
 
For  
 
DSM-5 
 
© Copyright 1992-2021 Sheehan DV 
 


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19. APPENDIX 10: FAGERSTRÖM TEST FOR CIGARETTE DEPENDENCE (FTCD) 
The FTCD will be provided to the clinical site and is not included here in its entirety. 
 
 


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20. APPENDIX 11: MINNESOTA NICOTINE WITHDRAWAL SCALE (MNWS) 
The MNWS will be provided to the clinical site and is not included here in its entirety. 
 
 


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21. APPENDIX 12: QUESTIONNAIRE ON SMOKING URGES – BRIEF VERSION 
(QSU-BRIEF) 
The QSU-BRIEF will be provided to the clinical site and is not included here in its entirety.  
 
 


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22. APPENDIX 13: SUMMARY OF CHANGES AMENDMENT 1 
The changes below were made to Protocol SBP-9330-101 Version 1.0 (FINAL / 22 April 2021) 
 
Major Changes 
 
• 
Exclusion criterion number 22 was revised based on FDA feedback and to enhance clarity. 
 
Detailed Changes 
 
• 
Section 4.2 Exclusion criteria (page 38).  Exclusion criterion number 22 was revised as follows: 
 
22. Consumption of other OTC prescription and over-the-counter medication not specifically 
excluded by Exclusion Criterion 21 including (health supplements and herbal remedies) within 7 
days prior to the first study drug administration (an exception is made for paracetamol 
[acetaminophen], which is allowed up to admission to the clinic). 
 
• 
Table 2 (page 19) footnote 7 was revised as follows: 
 
7 
Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): 
at Screening; on Day -1 (admission); at pre-dose on Days 1, 7, 14, and 1716; and at follow-up/EOS. 
 
• 
Table 7 (page 31) was revised as follows: 
 
A5 
6:2 
(1:1 [sentinel group] and 5:1 
[remaining subjects]) 
2400 mg 
(68 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose administration 
of SBP-9330 or placebo under 
fasting conditions on Day 1. 
 
• 
Added Appendix 13: Summary of Changes Amendment 1 
 
• 
In addition, the following minor changes were made: 
 
o Cover page and throughout the document:  Added Amendment 1 (Version 2.0 / 1 June 
2021) 
 
o Protocol synopsis has been updated to be consistent with Amendment 1 changes 
 
o Minor typographical errors, formatting updates and changes for clarification and 
consistency have also been made throughout the protocol. 
 
 
 


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23. APPENDIX 14: SUMMARY OF CHANGES AMENDMENT 2 
The changes below were made to Protocol SBP-9330-101 Version 2.0 (Amendment 1 / 1 June 
2021) 
 
Major Changes 
• A Clinical Laboratory Test timepoint was added to Part B (MAD) Day 3.   
• 
The protocol was updated to allow for the use of 75mg dose strength capsules to allow 
for intermediate dose levels during dose escalation. 
 
Detailed Changes 
 
• Table 2 Schedule of Activities – Part B (MAD Phase) was modified to add a Day 3 
Clinical Laboratory Test assessment: 
 
 
Footnote 7 – Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, 
hematology, and urinalysis): at Screening; on Day -1 (admission); at pre-dose on Days 1, 3, 7, 
14, and 16; and at follow-up/EOS. 
 
• Section 3.2 Data and Safety Monitoring Board (DSMB), Paragraph 2 was modified as 
follows: 
 
The DSMB will be comprised of voting members who are independent of the Sponsor and CRU 
and will, at a minimum, include a physicians experienced in drug safety, a clinical 
pharmacologist, and a biostatistician. The composition and operations of the DSMB will be 
detailed in a separate document that will serve as the Data and Safety Monitoring Plan (DSMP). 
• Section 3.3.1 Part A – SAD Phase with Nested Food-Effect Cohort was modified as 
follows: 
 
Screening of participants will occur within approximately 28 days of the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 
consent to participation will be admitted to the CRU for baseline evaluations before dosing 
(Day -1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. Subjects in Cohort A3 will have eligibility confirmed for Day -1 for fasted 
dose (Period 1) only and not for the fed dose (Period 2). 
 
• Section 3.4 Study Treatments was modified to include 75-mg formulation. 
 


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The following investigational products (IPs) will be administered according to the outlined dose 
levels in Sections 3.3.1 and 3.3.2. 
o Test product: SBP-9330 75-mg, 150-mg and 300-mg capsules  
o Placebo: Placebo to match SBP-9330 75-mg, 150-mg and 300-mg capsules 
 
• Section 4.1 Inclusion Criteria (inclusion criterion7) was modified as follows: 
 
7. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not 
donate sperm from the first admission to the CRU until 90 days after the last study drug 
administration. Adequate contraception for the male subject (and/or his female partner) includes 
the following: 
o Use of spermicide, hormonal contraceptives or an intrauterine device combined with at least 
one of the following forms of contraception: a diaphragm, a cervical cap, or a condom 
o Double-barrier method (e.g., condom with diaphragm or cervical cap) 
 
• Section 4.5 Concomitant Treatment was modified to include the following statement: 
 
Subjects receiving the COVID-19 vaccine should be fully vaccinated at least 14 days prior to 
receiving Investigational Product. 
 
• Section 5.1.1 SBP-9330 was modified as follows: 
 
SBP-9330 150 mg and 300 mg capsules are manufactured by PACE Laboratory (previously 
Velesco Pharmaceutical Services, Inc.) for oral administration. Small batches of 75 mg dose 
strength capsules will be prepared by the Altasciences pharmacy using a sponsor-supplied 
procedure. Each white gelatin capsule contains SBP-9330 sodium equivalent to 75 mg, 150 mg 
or 300 mg SBP-9330.  
 
• Section 5.1.2 Placebo was modified as follows: 
 
Placebo capsules matched to Sponsor’s SBP-9330 75, 150 and 300 mg capsules will be supplied 
by the Sponsor. The placebo formulation will be comprised of the same white gelatin capsule, 
filled with Avicel microcrystalline cellulose, without SBP-9330 (active ingredient). 
 
• Section 6.2 Blood Volume Collected was modified as follows: 
 
• 292 330 mL for Part B – MAD Phase (all cohorts) 
 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 100 of 104 
• Section 7.6 Serious Adverse Event Reporting was modified as follows: 
 
The CRU will notify any SAE to the Sponsor, without regard to causality, within 24 hours after 
becoming aware of its occurrence. The NIDA Project Official (Tanya Ramey, MD PhD Evan 
Herrmann, PhD) and Project Scientist (Evan Herrmann, PhD Tanya Ramey, MD PhD) will be 
notified of the SAE within 72 hours of the SAE occurrence via email. 
 
• Added Appendix 14: Summary of Changes Amendment 2 
 
• In addition, the following minor changes were made: 
 
o Cover page and throughout the document:  Added Amendment 2 (Version 3.0 / 
10 December 2021) 
 
o Protocol synopsis was updated to be consistent with Amendment 2 changes 
 
o Correction of typographical errors, formatting updates, and changes for 
clarification and consistency have been made throughout the protocol. 
 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 101 of 104 
24. APPENDIX 15: SUMMARY OF CHANGES AMENDMENT 3 
The changes below were made to Protocol SBP-9330-101 Version 3.0 (Amendment 2 / 
10 December 2021). 
 
Major Changes 
• A Smoker Phase (Part C) was added to the study to evaluate the safety, PK, and to 
explore the effects on smoking-related assessments of SBP-9330 in smokers, which is 
the target population for treatment with SBP-9330. 
 
Detailed Changes 
 
• Updated all relevant sections of the protocol to include Part C: Smoker Phase information 
including the study rationale, background information, study design, blood volume, and 
screening, safety, smoking, and PK assessments. The summary of the Part C: Smoker 
Phase is presented below. 
 
Healthy adult smokers will be randomized to receive either SBP-9330 or placebo orally 
in each of the 2 planned smoker cohorts. Each cohort will consist of 10 subjects randomly 
assigned in 4:1 (SBP-9330:placebo) ratio, for a total of 8 subjects receiving SBP-9330 
and 2 subjects receiving placebo.  
The proposed Smoker phase design and planned escalation are as follows: 
Cohort 
N (active:placebo) 
Dose  
Drug administrations 
C1 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
C2 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
Additional C3 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days 
 
Each subject will receive once daily oral administration of the assigned treatment under 
fasting conditions (SBP-9330 or placebo) for 14 consecutive days.  
The Smoker phase of the study may commence after completion of dosing the MAD 
phase of the study. The Smoker cohort daily dose will be less than or equal to the highest 
MAD dose for which complete safety and PK data are available.  
All relevant safety and plasma PK data will be reviewed by the DSMB before any dose 
escalation. The DSMB will be provided the randomization code to aide in the review. 
The dose levels proposed for Smoker cohorts may be adjusted during the course of the 
study based on preliminary safety and PK data.  
The Smoker phase will have a maximum of 3 cohorts. There are 2 planned cohorts and an 
additional cohort may be added depending on the emerging PK and safety data in the 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 102 of 104 
previous cohorts. A Smoker cohort daily dose level cannot be higher than the highest 
dose level tested in the MAD phase.  
All subjects who complete the study and those terminating early will be required to 
complete the End of study/Follow-up procedures. 
• The primary and secondary objectives in the Synopsis and Section 2. Study Objectives 
and Endpoints were updated to specify that the study population includes healthy 
nonsmokers and/or healthy smokers. 
 
• The following exploratory endpoints were added for Part C in the Synopsis and 
Section 2. Study Objectives and Endpoints: 
 
▪ Expired carbon monoxide (ECO) level  
▪ Plasma cotinine level 
▪ Number of cigarettes smoked (smoking log) 
▪ Minnesota Nicotine Withdrawal Scale (MNWS) responses 
▪ Questionnaire on Smoking Urges – Brief version (QSU-Brief) responses 
 
• Updated the Synopsis and Section 4.1 Inclusion Criteria to include criteria (#11 to #14) 
specific to Part C only. 
 
11. Are current tobacco cigarette smokers who smoke an average of 10 or more cigarettes 
per day in the 30 days prior to Screening  
12. Expired breath CO level ≥10 parts per million (ppm) at Screening and prior to the 
first study drug administration 
13. Positive test result for cotinine at Screening and prior to the first study drug 
administration 
14. Are not motivated to try to quit smoking from Screening through 30 days from the 
first study drug administration 
 
• Updated the Synopsis and Section 4.2 Exclusion Criteria to include criteria (#29 to #33) 
specific to Part C only. 
 
29. History of generalized rash reaction to any drugs 
30. Positive test result (except cotinine) for alcohol and/or drugs of abuse at Screening or 
prior to the first study drug administration 
31. Use of smoking cessation aids (NRT, bupropion, or varenicline) within 30 days prior 
to the first study drug administration 
32. Unable to abstain from smoking tobacco cigarettes for at least 1 hour before and 
2 hours after study drug administration 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 103 of 104 
33. Unable to abstain from using nicotine-containing products other than tobacco 
cigatettes (e.g., pipes, cigars, e-cigarettes or vapes, nicotine topical patches, nicotine gum, 
or nicotine lozenges) during the study 
• Updated the Synopsis and added Section 8.5 Smoking Assessment (Part C only) to 
present analysis of smoking data.  
 
• Added Table 3. Schedule of Activities – Part C (Smoker Phase)  
 
• Updated Table 5. Adaptive Features and Boundaries to include possibility of adapting the 
dose level and other adaptive features for the Smoker cohorts. 
 
• Added the following restriction to Section 4.4. Lifestyle and/or Dietary Requirements 
 
For the Smoker cohorts, subjects will abstain from smoking tobacco cigarettes for at least 
1 hour before and 2 hours after study drug administration. Subjects will also abstain from 
using nicotine-containing products other than tobacco cigarettes (e.g., pipes, cigars, 
e-cigarettes or vapes, nicotine topical patches, nicotine gum, or nicotine lozenges) or 
other tobacco products (cigars, cigarillos, pipes) during the study. 
 
• Added to Section 6.1.3 vital signs normal ranges. 
• Added the following sections and appendix: 
 
▪ Section 6.4. Smoking Assessments for Part C only  
▪ Section 6.4.1. Fagerström Test for Cigarette Dependence (FTCD) and 
Appendix 10 
▪ Section 6.4.2. Smoking Time-Line Follow-back (TLFB)  
▪ Section 6.4.3. Expired Carbon Monoxide (CO) Level 
▪ Section 6.4.4. Blood Sampling for Cotinine 
▪ Section 6.4.5. Smoking Log 
▪ Section 6.4.6. Minnesota Nicotine Withdrawal Scale (MNWS) and Appendix 11 
▪ Section 6.4.7. Questionnaire on Smoking Urges – Brief version (QSU-Brief) and 
Appendix 12 
 
• Updated the Synopsis and Section 8.5 Smoking Assessments (Part C only) to indicate 
that expired CO values, cotinine levels, number of cigarettes smoked, MNWS responses, 
and QSU-Brief responses will be summarized using descriptive statistics. 
 
• Added Appendix 15: Summary of Changes Amendment 3 
 
• Updated the Sponsor address from 12707 High Bluff Drive, Suite 200 San Diego, CA 
92130 USA to 9920 Pacific Heights Blvd, Suite 150 San Diego, CA 92121 USA 
 
• Updated the manufacturer for the Test Product and Placebo from Velesco Pharmaceutical 
Services, Inc. to PACE Laboratory (previously Velesco Pharmaceutical Services, Inc.) 


Protocol No: SBP-9330-101 
Altasciences Project Number: CNO-P5-319 
 
Version 4.0 (Amendment 3) - 2022/09/14 
Page 104 of 104 
 
• In addition, the following minor changes were made: 
 
o Cover page and throughout the document: Added Amendment 3 (Version 4.0 / 
14 September 2022) 
 
o Correction of typographical errors, formatting updates, and changes for 
clarification and consistency have been made throughout the protocol. 

SAP_001.pdf: 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
For: 
Camino Pharma, LLC 
 
 
 
PROTOCOL No. SBP-9330-101 
 
 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, FIRST-IN-HUMAN 
STUDY TO ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF 
SINGLE AND MULTIPLE ASCENDING DOSES OF SBP-9330 (WITH A NESTED FOOD-
EFFECT ARM) AFTER ORAL ADMINISTRATION IN HEALTHY SUBJECTS 
 
Altasciences Project No. CNO-P5-319 
 
Prepared by: 
Altasciences Company Inc. 
575 Armand-Frappier Boulevard 
Laval, Quebec 
Canada, H7V 4B3 
 
 
Version: Final 1.1 
Date: 2023/03/10 
 


 
 
 
Protocol No. SBP-9330-101 |Altasciences Project No. CNO-P5-319 | Final Version 1.1 | 2023/03/10 
Page 2 of 47 
STATISTICAL ANALYSIS PLAN APPROVAL 
We have carefully read this statistical analysis plan and agree it contains the necessary 
information required to handle the statistical analysis of study data. 
 
 
 
 
Ramadevi Vemuri 
Senior Biostatistician 
Altasciences Company, Inc. 
 
Date  
 
 
 
 
Olivier Vachon 
Supervisor, Pharmacology 
Altasciences Company, Inc. 
 
Date  
 
 
On behalf of the Sponsor: 
 
 
 
 
Vijay Hingorani, MD, PhD 
Study Medical Monitor 
Camino Pharma, LLC 
 
Date  
 
 
16-Mar-2023
17MAR2023
Olivier Vachon
Digitally signed by Olivier Vachon 
Reason: I attest to the accuracy 
and integrity of this document 
Date: 2023.03.20 10:31:19 -04'00'


 
 
 
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VERSION CONTROL 
Version 
Date 
Author 
Description of Changes 
Final v1.0 
2022/02/11 
Ramadevi Vemuri/ 
Olivier Vachon 
Not Applicable 
Final v1.1 
2023/03/10 
Ramadevi Vemuri/ 
Olivier Vachon 
Added Part C details 
 
 
 
 
 
 
 
 
 


 
 
 
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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN APPROVAL .....................................................................2 
VERSION CONTROL .............................................................................................................3 
TABLE OF CONTENTS ..........................................................................................................4 
TABLE OF TABLES ...............................................................................................................6 
ABBREVIATIONS ..................................................................................................................7 
1 
INTRODUCTION ...........................................................................................................8 
2 
STUDY OBJECTIVES....................................................................................................9 
3 
STUDY DESIGN .......................................................................................................... 11 
3.1 
General Description .................................................................................................. 11 
3.1.1 
Part A – SAD Phase with Nested Food-Effect Cohort........................................ 11 
3.1.2 
Part B - MAD Phase......................................................................................... 13 
3.1.3 
Part C - Smoker Phase...................................................................................... 14 
3.2 
Determination of Sample Size ................................................................................... 16 
3.3 
Study Treatments ...................................................................................................... 16 
3.4 
Study Procedures ...................................................................................................... 16 
3.5 
Randomization and Unblinding Procedures................................................................ 16 
4 
ANALYSIS POPULATIONS ........................................................................................ 18 
5 
STUDY SUBJECTS ...................................................................................................... 19 
5.1 
Disposition ............................................................................................................... 19 
5.2 
Protocol Deviations................................................................................................... 20 
6 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................. 21 
7 
PHARMACOKINETIC ANALYSIS ............................................................................. 22 
7.1 
Missing Values ......................................................................................................... 22 
7.2 
Measurements Below the Lower Limit of Quantitation ............................................... 22 
7.3 
Actual Time .............................................................................................................. 22 
7.4 
Non-Compartmental Analysis.................................................................................... 22 
7.5 
Pharmacokinetic Statistical Methodology................................................................... 25 
7.5.1 
Summary Statistics........................................................................................... 25 
7.5.2 
Statistical Analysis ........................................................................................... 26 
7.5.3 
Smoking Assessment (Part C only) ................................................................... 27 
8 
SAFETY ANALYSIS ................................................................................................... 28 
8.1 
Adverse Events ......................................................................................................... 29 


 
 
 
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8.2 
Clinical Laboratory Evaluations................................................................................. 30 
8.3 
Vital Signs ................................................................................................................ 31 
8.4 
Physical Examination Findings .................................................................................. 33 
8.5 
12-Lead ECG Findings.............................................................................................. 33 
8.6 
Columbia Suicide Severity Rating Scale (C-SSRS) .................................................... 34 
9 
DATA HANDLING AND PRESENTATION ................................................................ 35 
9.1 
Safety Analysis Presentation...................................................................................... 35 
9.2 
Pharmacokinetic Analysis Presentation ...................................................................... 36 
9.3 
Analysis Timepoints ................................................................................................. 37 
9.4 
Methods for Handling Missing Data .......................................................................... 37 
10 
INTERIM ANALYSES AND DATA SAFETY MONITORING .................................... 38 
11 
CHANGES TO PROTOCOL-SPECIFIED ANALYSES ................................................ 39 
12 
GENERAL INFORMATION RELATED TO DATA PRESENTATIONS ...................... 40 
APPENDIX A 
STUDY SCHEDULE(S) ......................................................................... 41 


 
 
 
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TABLE OF TABLES 
Table 1: Objectives and related endpoints ................................................................................. 9 
Table 2: Part A – SAD Phase with Nested Food-Effect Cohort Design and Dose Levels ...........11 
Table 3: Part B - MAD Phase Design and Dose Levels ............................................................14 
Table 4: Part C - Smoker Phase Design and Dose Levels .........................................................15 
Table 5: Data presentations for study subject information ........................................................19 
Table 6: Data presentations for demographic and other baseline characteristics.........................21 
Table 7: Pharmacokinetic Parameters of SBP-9330 in Plasma ..................................................24 
Table 8: Data presentations for safety assessments ...................................................................28 
Table 9: Vital Sign Recording Schedule – SAD Phase .............................................................32 
Table 10: Vital Sign Recording Schedule – MAD and Smoker Phase .......................................32 
Table 11: ECG Recording Schedule – SAD Phase ...................................................................33 
Table 12: ECG Recording Schedule – MAD and Smoker Phase ...............................................34 
Table 13: Schedule of Activities – Part A (SAD Phase with Nested Food-Effect Cohort) ..........41 
Table 14: Schedule of Activities – Part B (MAD Phase) ..........................................................43 
Table 15: Schedule of Activities – Part C (Smoker Phase)........................................................45 
 


 
 
 
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ABBREVIATIONS 
AE 
Adverse event 
ANOVA 
Analysis of variance 
ATC 
Anatomical therapeutic chemical 
BMI 
Body mass index 
CI 
Confidence interval 
CRF 
Case report form 
CSR 
Clinical study report 
DSMB 
Data safety monitoring board 
DMP 
Data management plan 
ECG 
Electrocardiogram 
EOS 
End of study 
ICH 
International Council for Harmonisation 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
Pharmacokinetic(s) 
PT 
Preferred term 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SOC 
System organ class 
SOP 
Standard operating procedure 
TEAE 
Treatment-emergent adverse event 
TFLs 
Tables, figures, and listings 
WHO-DDE 
World health organization drug dictionary- enhanced 
 
 
 


 
 
 
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1 INTRODUCTION 
SBP-9330 is a potent and selective mGlu2 positive allosteric modulator (PAM) with excellent 
drug-like properties including oral bioavailability and metabolic stability. Importantly, SBP-9330 
reduces nicotine self-administration and cue-induced nicotine reinstatement in rats without 
affecting natural food reward. In addition, SBP-9330 was well-tolerated and safe in pivotal (good 
laboratory practice [GLP]) 14-day toxicology studies in rats and dogs. 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and 
procedures to be implemented for the analyses of data from protocol SBP-9330-101. Pre-
planning of analyses reduces the potential for bias and often reduces disputes between sponsor 
and the regulatory authority regarding the validity of the results. The same principles apply to 
supportive and/or sensitivity analyses. These analyses must be prospectively specified. (Good 
Review Practice: Clinical Review of Investigational New Drug Applications, December 2013).  
The analyses described in the SAP are based upon the final protocol version 4.0, Amendment 3 
dated 2022/09/14. 
 
 


 
 
 
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2 STUDY OBJECTIVES 
The objectives of the study and corresponding study endpoints are detailed in Table 1. 
Table 1: Objectives and related endpoints 
Objective 
Endpoint 
Analysis 
Primary  
To assess the safety and 
tolerability of single and multiple 
ascending oral doses of SBP-9330 
in healthy nonsmokers and 
healthy smokers  
  
 
Incidence and severity of adverse events 
(AEs) for subjects administered SBP-9330 
compared to placebo  
 
Changes in vital signs, physical 
examination findings, ECG findings, C-
SSRS questionnaire results, and clinical 
laboratory results for subjects administered 
SBP-9330 compared to placebo  
Refer to Section 8 
Secondary  
To determine single and multiple 
oral dose pharmacokinetics (PK) 
of SBP-9330 in healthy 
nonsmokers and healthy smokers  
Pharmacokinetic (PK) parameters, where 
appropriate, will be determined for SBP-9330 
from individual concentration-time profiles in 
plasma.  
The following PK parameters will be evaluated 
for each study phase: 
Part A (SAD Phase): 
 
Cmax, Tmax, AUC0-24, AUC0-T, AUC0-∞, 
Thalf, CL/F, and Vz/F  
Part B (MAD Phase) and Part C ( Smoker 
Phase): 
 
Day 1: Cmax, Tmax, AUC0-24, AUC0-T  
 
Days 7, 11, 12, and 13: Ctrough  
 
Day 14: Ctrough, Cmax, Tmax, Cτ, AUCτ, 
AUC0-T, effective Thalf, Thalf, CL/Fss, 
Vz/Fss, RAC(Cmax), RAC(AUC)  
For all study parts, additional PK parameters 
will be estimated for supportive purposes. 
Refer to Section 7 
To explore the effect of food on 
the single oral dose PK of SBP-
9330 in healthy nonsmokers  
Main PK parameters will be determined to 
assess the effect of food after a single oral dose 
of 600 mg SBP-9330.  
For Cohort A3 (Food Effects) only, the PK 
parameters specified above for Part A will be 
estimated on Day 1 and Day 8. Inferential 
statistical analysis will be performed on the 
following main PK parameters: 
 
Cmax, AUC0-T, and AUC0-∞ 
In addition, Tmax will be summarized 
descriptively 
Refer to Section 7 
 
 


 
 
 
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Exploratory  
To explore the effect of SBP-9330 
on smoking-related assessments  
 
 
Expired carbon monoxide (ECO) level 
 
Plasma cotinine level 
 
Number of cigarettes smoked 
(smoking log) 
 
Minnesota Nicotine Withdrawal Scale 
(MNWS) responses 
 
Questionnaire on Smoking Urges – 
Brief version (QSU-Brief) responses  
 
 
 
 
 


 
 
 
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3 STUDY DESIGN  
3.1 
General Description 
This is a single-center, first-in-human, randomized, double-blind, placebo-controlled, single- and 
multiple-dose escalating study incorporating a food-effect cohort.  
The study will include 3 parts:  
 
 Part A: SAD phase with a nested food-effect cohort  
 Part B: MAD phase  
 Part C: Smoker phase  
 
 
Each cohort will receive SBP-9330 in an ascending dose order. 
Part A – SAD phase with nested food-effect cohort will include approximately 40 subjects (up to 
5 cohorts of 8 subjects) and Part B – MAD phase will include approximately 40 subjects (up to 4 
cohorts of 10 subjects), and Part C – Smoker phase will include approximately 30 subjects (up to 3 
cohorts of 10 subjects). Therefore, up to 110 subjects will be included in the study.  
All subjects who complete the study and those terminating early will be required to complete the 
End of study (EOS)/Follow up procedures.  
3.1.1 Part A – SAD Phase with Nested Food-Effect Cohort 
Screening of participants will occur within approximately 28 days of the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 
consent to participation will be admitted to the CRU for baseline evaluations before dosing (Day 
-1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. Subjects in Cohort A3 will have eligibility confirmed for Day -1 for fasted 
dose (Period 1) only and not for the fed dose (Period 2). 
Eligible subjects will be randomized to SBP-9330 or placebo in 1 of the 5 ascending dose 
cohorts (8 subjects per cohort) to have a total of 6 subjects receiving SBP-9330 and 2 subjects 
receiving placebo. All cohorts in the fasting state will be dosed according to a sentinel dosing 
design to ensure optimal safety. Initially, 2 subjects will be dosed; 1 subject will be dosed with 
SBP-9330 and 1 subject with placebo. If the safety and tolerability results of the first 24 hours 
following dosing for the initial subjects are acceptable to the Investigator, the other 6 subjects (5 
active and 1 placebo) may be dosed approximately 24 hours after dosing of the sentinel group.  
Furthermore, one single-dose, two-period, crossover, food-effect cohort will be integrated into a 
SAD cohort (Cohort A3).  
The proposed SAD design and planned escalation are presented in Table 2. 
Table 2: Part A – SAD Phase with Nested Food-Effect Cohort Design and Dose Levels 
Cohort 
N (active:placebo) 
Dose (mg) 
Drug administration 
A1 
6:2  
(1:1 [sentinel group] and 
5:1 [remaining subjects])  
150 mg 
(1 × 150-mg SBP-9330 
capsule or matched 
Single oral dose 
administration of SBP-9330 
or placebo under fasting 


 
 
 
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Cohort 
N (active:placebo) 
Dose (mg) 
Drug administration 
placebo) 
conditions on Day 1. 
A2 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
300 mg 
(1 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose 
administration of SBP-9330 
or placebo under fasting 
conditions on Day 1. 
A31 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects] 
for Period 1 only) 
600 mg 
(2 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose 
administration of SBP-9330 
or placebo under fasting 
conditions on Day 1 of 
Period 1 and fed conditions 
on Day 1 of Period 2. 
Washout between the 2 
periods will be at least 
7 to 14 days. 
A4 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
1200 mg 
(4 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose 
administration of SBP-9330 
or placebo under fasting 
conditions on Day 1. 
A5 
6:2 
(1:1 [sentinel group] and 
5:1 [remaining subjects]) 
2400 mg 
(6 × 300-mg SBP-9330 
capsule or matched 
placebo) 
Single oral dose 
administration of SBP-9330 
or placebo under fasting 
conditions on Day 1. 
1 2-period, food-effect cohort 
For Cohorts A1, A2, A4, and A5, each subject will receive the assigned treatment (SBP-9330 or 
placebo) under fasting conditions.  
For Cohort A3 (2 period food-effect cohort), each subject will receive the randomly assigned 
treatment (SBP-9330 or placebo) under fasting conditions in Period 1. After a 7- to 14-day 
washout period, they will receive the same single dose of SBP-9330 or placebo in a fed state in 
Period 2, 30 minutes after the start of an FDA High-Fat and High-Calorie Breakfast. Escalation 
to Cohort A4 will be based only on the fasting period safety and PK and may proceed in parallel 
to the A3 fed period. 
All cohorts in the fasting state will be dosed according to a sentinel dosing design to ensure 
optimal safety. Initially, 2 subjects will be dosed; 1 subject will be dosed with SBP-9330 and 1 
subject with placebo. If the safety and tolerability results of the first 24 hours following dosing 
for the initial subjects are acceptable to the Investigator, the other six subjects (5 active and 1 
placebo) may be dosed approximately 24 hours after dosing of the sentinel group.  
Escalation to the next higher dose will only proceed if none of the stopping criteria have been 
reached and when the safety and tolerability and plasma PK analysis of the previous dose, 


 
 
 
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including delayed emergence of significant AEs in earlier cohorts, are acceptable to the 
Investigator, Sponsor and DSMB. 
The SAD phase will have a maximum of 5 cohorts. The number of cohorts may be changed at 
the discretion of the Sponsor depending on the emerging safety and plasma PK data from the 
previous cohorts. The dose levels proposed for SAD cohorts may be adjusted during the course 
of the study based on preliminary safety and plasma PK data but escalation will not be more than 
3-fold the previous dose. 
For Cohorts A1, A2, A4, and A5:  
 Subjects will be confined to the CRU from at least 10 hours prior to drug administration 
until approximately 48 hours after study drug administration. Subjects will therefore be 
confined for 4 days and 3 nights (Day -1 to Day 3). However, they may be advised to stay 
longer at the CRU for safety reasons, if judged necessary by an Investigator. 
 Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 8±1). 
 Total study duration: up to 38 days (including Screening) 
For Cohort A3 (food-effect cohort):  
 In each period, subjects will be confined to the CRU from at least 10.5 hours prior to 
drug administration until approximately 48 hours after study drug administration. 
Subjects will therefore be confined for 4 days and 3 nights (Day -1 to Day 3) in each 
period. However, they may be advised to stay longer at the CRU for safety reasons, if 
judged necessary by an Investigator. 
 Washout period between treatment administrations: at least 7 to 14 calendar days 
 Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 8±1) of Period 2. 
 Total study duration: up to 46 days (including Screening) 
3.1.2 Part B - MAD Phase 
Screening of participants will occur within approximately 28 days prior to the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 
consent to participation will be admitted to the CRU for baseline evaluations before dosing 
(Day -1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. 
Subjects will be randomized to SBP-9330 or placebo in 1 of the 3 ascending dose cohorts 
(10 subjects per cohort in 4:1 [SBP-9330:placebo] ratio) to have a total of 8 subjects receiving 
SBP-9330 and 2 subjects receiving placebo. An additional MAD cohort (Cohort B4) may be 
added at the discretion of the Sponsor depending on emerging safety and PK data from previous 
cohorts. 
The proposed MAD design and planned escalation are presented in Table 3. 
 
 


 
 
 
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Table 3: Part B - MAD Phase Design and Dose Levels 
Cohort 
N 
(active:placebo) 
Dose  
Drug administrations 
B1 
8:2 
adaptive  
Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
B2 
8:2 
adaptive  
Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
B3 
8:2 
adaptive  Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
Additional 
B4 
8:2 
adaptive 
Once daily oral administrations of SBP-9330 or placebo 
for 14 consecutive days (Days 1 to 14) under fasting 
conditions 
Each subject will receive once daily oral administration of the assigned treatment and dose under 
fasting conditions (SBP-9330 or placebo) for 14 consecutive days.  
The MAD phase of the study may commence in parallel to the SAD or thereafter. The decision 
on how early the MAD phase of the study may be started and the doses to be administered will 
be determined by the Sponsor after consultation with the DSMB based on emerging safety and 
PK data. The first MAD daily dose will be less than or equal to an already well-tolerated SAD 
dose for which complete safety and PK data are available.  
All relevant safety and available plasma PK data will be reviewed by the DSMB before any dose 
escalation. The dose levels proposed for MAD cohorts may be adjusted during the course of the 
study based on preliminary safety and PK data. The dosing frequency may also be changed from 
once daily to twice daily, without changing the total daily dose outlined in the protocol.  
The MAD phase will have a maximum of 4 cohorts. The number of cohorts may be changed at 
the discretion of the Sponsor depending on the emerging safety and PK data from the previous 
cohorts. The increase from one dose level to the next dose level will not be more than 3-fold. A 
MAD daily dose level cannot be higher than the highest dose level tested in SAD.  
Subjects will be confined to the CRU from at least 10 hours prior to drug administration until 
approximately 48 hours after last study drug administration. Subjects will therefore be confined 
for 17 days and 16 nights (Day -1 to Day 16). 
Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 21±1). 
3.1.3 Part C - Smoker Phase 
Screening of participants will occur within approximately 28 days prior to the first scheduled 
administration of study medication. Screening data will be reviewed to determine subject 
eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria and who 
consent to participation will be admitted to the CRU for baseline evaluations before dosing 


 
 
 
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(Day -1). All baseline safety evaluation results should be available prior to dosing and continued 
eligibility confirmed. 
Subjects will be randomized to SBP-9330 or placebo in 1 of the 2 planned Smoker cohorts 
(10 subjects per cohort in 4:1 [SBP-9330:placebo] ratio) to have a total of 8 subjects receiving 
SBP-9330 and 2 subjects receiving placebo. An additional Smoker cohort (Cohort C3) may be 
added at the discretion of the Sponsor depending on emerging safety and PK data from previous 
cohorts. 
Table 4: Part C - Smoker Phase Design and Dose Levels 
Cohort 
N (active:placebo) 
Dose  
Drug administrations 
C1 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
C2 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days  
Optional C3 
8:2 
adaptive 
Once daily oral 
administrations for 14 
consecutive days 
 
Each subject will receive once daily oral administration of the assigned treatment and dose under 
fasting conditions (SBP-9330 or placebo) for 14 consecutive days.  
The Smoker phase of the study may commence after completion of dosing the MAD phase of the 
study. The Smoker cohort daily dose will be less than or equal to highest MAD dose for which 
complete safety and PK data are available.  
All relevant safety and available plasma PK data will be reviewed by the DSMB before any dose 
escalation. The DSMB will be provided the randomization code to aide in the review for Part C. 
The dose levels proposed for Smoker cohorts may be adjusted during the course of the study 
based on preliminary safety and PK data.  
The Smoker phase will have a maximum of 3 cohorts. The number of cohorts may be changed at 
the discretion of the Sponsor depending on the emerging safety and PK data from the previous 
cohorts.  
Subjects will be confined to the CRU from at least 10 hours prior to drug administration until 
approximately 48 hours after last study drug administration. Subjects will therefore be confined 
for 17 days and 16 nights (Day -1 to Day 16). 
Subjects will return for a follow-up visit approximately 5 days after the last PK blood 
sample/discharge (Day 21±1). 
 
 


 
 
 
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3.2 
Determination of Sample Size 
Sample size is based on the estimate of the number of subjects necessary to obtain a clinical 
assessment regarding the drug’s safety profile over the planned dose range and was not based on 
statistical considerations. 
3.3  Study Treatments 
The following investigational products (IPs) will be administered according to the outlined dose 
levels in Table 2 and Table 3. 
 Test product: SBP-9330 75-mg, 150-mg and 300-mg capsules  
 Placebo: Placebo to match SBP-9330 75-mg, 150-mg and 300-mg capsules 
3.4 
Study Procedures 
For complete details on the study assessments to be performed for each study period, refer to 
APPENDIX A.  
3.5 
Randomization and Unblinding Procedures 
The CRU will generate the randomization code for each cohort with a computer program 
according to the study design, the number of subjects and the treatment to be administered. Once 
generated, the randomization code will be final and will not be modified. 
Subjects enrolled in the SAD sentinel groups will be randomized 1:1 to receive SBP-9330 or 
matching placebo while the rest of the subjects in the cohort will be randomized 5:1 to receive 
SBP-9330 or matching placebo. Subjects enrolled in the MAD and Smoker cohorts will be 
randomized 8:2 to receive SBP-9330 or matching placebo. 
Subjects who sign the informed consent form (ICF) and are randomized but do not receive the 
study treatment may be replaced. Subjects who sign the ICF, are randomized and received at 
least 1 dose of the study treatment, and are withdrawn prematurely from the study, may be 
replaced by an equal number of newly enrolled subjects. A new unique randomization number 
will be assigned to the replacement subject. The replacement list will be provided and will be 
identical to the original randomization scheme. 
This study is double-blind. Treatment assignments (active or placebo) will be blinded to the 
investigator, subjects and all clinical and research staff for the entire study, with the exception of 
designated pharmacy staff who will remain unblinded in order to dispense active drug or 
placebo.  
The study blind will be broken upon completion of the clinical study and after the study database 
has been locked.  
During the study, the randomization code must not be broken except in emergency situations 
where the identification of a subject’s study treatment is required by the qualified investigator for 
further treatment to the subject, to assess cohort stopping rules or to complete a SAE report. 
Randomization information will be held by designated individual(s). When possible, the 
qualified investigator should discuss the emergency with the Sponsor prior to unblinding. The 
date and reason for breaking the blind must be recorded.  


 
 
 
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The results of the blinded safety and available PK data will be made available to the DSMB 
group before proceeding with the next dose level. The bioanalytical facility will preserve the 
blind by reassigning alternative subject numbers to the interim data before they are made 
available to the PK facility and Sponsor; these alternative subject numbers will be assigned by 
the lab at the time of sample analysis. For the food-effect cohort (Cohort A3), the clinic will 
provide the lab with the meal condition for each subject, and the lab will translate this 
information to the corresponding alternative subject number and will provide the resulting list 
comprised of alternative number and associated meal condition to the PK scientist. These 
measures will ensure that whenever possible, the DSMB members remain blinded during their 
reviews and throughout the clinical part of the study. Based on review of the safety data, the 
DSMB may request randomization information, if necessary, to make appropriate dose 
escalation decisions and this unblinding will be documented.  
At the request of the Sponsor, specified individuals may be unblinded and receive the 
randomization information prior to database lock. This unblinding will be fully documented and 
all unblinded individuals advised that they must not distribute randomization information to any 
blinded parties. 
 
 


 
 
 
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4 ANALYSIS POPULATIONS 
 Safety population: The safety population will include all subjects who received at least 1 
dose of one of either the SBP-9330 or placebo. 
The number of subjects who were included, who discontinued, and who completed the 
study will be tabulated. The primary reasons for discontinuation will be provided. 
 Pharmacokinetic Population: The PK population will include all subjects who have 
received at least 1 dose of SBP-9330 and have at least 1 PK concentration after dosing. 
Subjects who do not complete the sampling schedule of one or more study days may be 
included in the PK and statistical populations for only the PK parameters that are judged 
not to be affected by the missing sample(s).  
Subjects with protocol deviations or adverse events (e.g., vomiting) that could be 
considered to have an impact on the PK results may be excluded from the PK population. 
Excluded subjects will be tabulated with the exclusion reason in the PK listings. 
 
 
 


 
 
 
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5 STUDY SUBJECTS 
Disposition and protocol deviations will be summarized and listed as described in Table 5. The 
disposition table and listing will be presented for the randomized subjects. Protocol deviations 
will be presented for the safety population. 
Table 5: Data presentations for study subject information  
Data 
Variables 
Presentation 
Disposition and analysis 
population 
Subject, completion status (i.e., 
completed or withdrawn), reason for 
withdrawal, analysis population 
determination 
Summary Table: 
 
N of subjects 
randomized 
 
N and % of subjects 
who completed the 
study 
 
N and % of subjects 
discontinued from the 
study by primary reason 
for discontinuation  
 
N and % of subjects 
included in each of the 
analysis populations 
T14.1.1.1 
T14.1.1.2 
T14.1.1.3 
Listings: 
 Disposition and 
completion/discontinuation 
L16.2.1 
 Exclusions from analysis 
population 
L16.2.3 
Protocol deviations 
Protocol deviations 
Listings: 
 General deviations 
L16.2.2.1 
 Blood sample collection time 
deviations 
L16.2.2.2 
 Inclusion/Exclusion Criteria 
violations 
L16.2.2.3 
 
5.1 
Disposition 
Subject disposition will be summarized for all subjects randomized in this study, and frequency 
(percentages) of subjects who completed the study, the reason for study discontinuation, and the 


 
 
 
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number of subjects who have been included in each study population. The percentages will be 
calculated using the number of subjects randomized as denominator.  
A listing of subject disposition and completion/discontinuation will be provided. A listing of 
subjects included in each of the analysis populations will also be provided. 
5.2 
Protocol Deviations 
A listing of all protocol deviations will be provided. Separate listings will be generated for blood 
sampling time deviations for SBP-9330. Samples taken outside of the windows mentioned in 
Altasciences SOP MAP-6014 will be captured as blood sampling time-related deviations. 
Deviations will be collected in the clinic deviation tracking system (DTS) and presented as 
entered in a general protocol deviation listing. 
For blood sampling time deviations, information will be derived programmatically. 
 
 


 
 
 
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6 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Unless otherwise specified, all available data will be listed and summary tables for demographics 
and other baseline characteristics will be presented for each analysis population as detailed in 
Table 6.  
Table 6: Data presentations for demographic and other baseline characteristics  
Data 
Variables 
Presentation 
Demographics and  
baseline characteristics 
Sex, age, race, height, body weight 
and BMI 
Listing and summary tables by 
analysis populations  
L16.2.4.1 
T14.1.2.1.1 
T14.1.2.1.2 
T14.1.2.1.3 
T14.1.2.2.1 
T14.1.2.2.2 
T14.1.2.2.3 
Medical history 
All medical history findings 
Listing 
Note: includes coded terms 
(system organ class [SOC] and 
preferred term [PT]) 
L16.2.4.2 
Prior medications 
All medications taken prior to study 
drug administration  
 
Listing 
Note: includes coded terms 
(anatomic therapeutic chemical 
[ATC] level 1 and preferred 
name) 
L16.2.4.3 
 
 
 


 
 
 
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7 PHARMACOKINETIC ANALYSIS 
The PK analysis will be carried out according to Altasciences Standard Operating Procedures 
(SOPs). 
7.1 
Missing Values 
The lack of concentration values due to failure to collect the sample, a lost or compromised 
sample or due to the subject’s early termination from the study will be considered “missing” in 
the dataset, and no imputation will be done.  
If the actual collection time of a post-dose PK sample is unknown, but a valid concentration 
value has been measured, the sample will be set to missing in the PK analysis and will be 
presented in the listings as excluded from descriptive statistics. Unknown pre-dose collection 
times will be handled on a case-by-case basis. 
7.2 
Measurements Below the Lower Limit of Quantitation 
Concentration values below the lower limit of quantitation (LLOQ) associated with pre-dose and 
post-dose collection times will be replaced with zero for the non-compartmental analyses (NCA); 
additional rules for samples that are below the LLOQ, if applicable.  
Concentration values below the LLOQ will be replaced with zero for mean PK profile 
representations as well as for descriptive statistic calculations. 
7.3 
Actual Time 
The NCA analysis will be based on the actual sampling times, except for predose samples, which 
will always be reported as zero, regardless of time deviations, provided that they were collected 
prior to dosing.  
The individual concentration/time profiles will be presented using actual sampling times whereas 
the mean concentration/time profiles and tables presenting summary statistics of concentration 
time data will be presented using nominal sampling times.  
Actual times will be listed in the report. 
7.4 
Non-Compartmental Analysis 
The following configuration for the NCA analysis (with Phoenix® WinNonlin® version 8, or 
higher) will be used:  
 Data: Serial sampled data  
 Model/Dose options Type: Plasma (200 -202) / Extravascular  
 AUC Calculation Method: Linear Up Log Down  
 Lambda Z (λz) calculation: Best fit method for λz Linear-Log regression  
Reasons for excluding PK parameters will include the following: 
 AUC: AUC parameters will not be estimated if less than 3 consecutive measurable 
concentrations are observed.  
 PK parameters requiring λz estimation (e.g., AUC0-∞ and Thalf) will be set to Not Reported 
(NR) in the Tables and Listings if they meet one of the following:  
o R2 < 0.8  
o Extrapolated area > 20%  


 
 
 
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o 3 time points used for terminal phase estimation include Cmax  
The PK parameters for SBP-9330 in plasma are presented in Table 7. 


 
 
 
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Table 7: 
Pharmacokinetic Parameters of SBP-9330 in Plasma 
PK Parameter 
Definition 
Part A: SAD Phase 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration 
AUC0-24 
Area under the concentration time curve from time 0 (dose administration) to 
24 hours 
AUC0-T 
Area under the concentration time curve from time 0 (dose administration) to 
the time of last quantifiable concentration (Tlast) 
AUC0-∞ 
Area under the concentration time curve extrapolated to infinity, calculated as 
AUC0-T + Clast/λZ, where Clast is the measured concentration at time Tlast 
Thalf 
Terminal elimination half-life, calculated as ln(2)/λZ 
CL/F 
Apparent total clearance, calculated as Dose/AUC0-∞ 
Vz/F 
Apparent volume of distribution, calculated as Dose/λZ * AUC0-∞ 
Cmax/D 
Dose-normalized Cmax 
AUC0-T/D 
Dose-normalized AUC0-T 
AUC0-∞/D 
Dose-normalized AUC0-∞ 
Parts B and C: MAD nonsmoker and smoker Phases, Day 1: 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration 
AUC0-24 
Area under the concentration time curve from time 0 (dose administration) to 
24 hours 
AUC0-T 
Area under the concentration time curve from time 0 (dose administration) to 
the time of last quantifiable concentration (Tlast) 
Cmax/D 
Dose-normalized Cmax 
AUC0-24/D 
Dose-normalized AUC0-24 
AUC0-T/D 
Dose-normalized AUC0-T 
Parts B and C: MAD nonsmoker and smokerPhases, Day 14: 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration; if it occurs at more than one time 
point, Tmax is defined as the first time point with this value 
Cτ 
Concentration at the end of the dosing interval. Observed concentration, 
otherwise the predicted concentration value will be calculated as per Phoenix® 
WinNonlin®’s built-in rules for interpolation/extrapolation, and subject to the 
criteria for PK parameters requiring λz estimation. 
AUCτ 
Area under the concentration time curve over the dosing interval at steady state, 


 
 
 
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calculated from 0 to 24 hours (dosing interval)  
AUC0-T 
Area under the concentration time curve from time 0 (dose administration) to 
the time of last quantifiable concentration (Tlast) 
Thalf 
Terminal elimination half-life, calculated as ln(2)/λZ 
Thalf, eff 
Effective half-life, calculated as  
τ * ln2 /ln(Rac(AUC)/( Rac(AUC)-1)), where τ is 24 hours1 
CL/Fss 
Apparent total clearance at steady state, calculated as Dose/AUCτ  
Vz/Fss 
Apparent volume of distribution at steady state, calculated as Dose/λZ * AUCτ  
Cmax/D 
Dose-normalized Cmax 
AUCτ/D 
Dose-normalized AUCτ 
AUC0-T/D 
Dose-normalized AUC0-T 
Rac(Cmax) 
Accumulation ratio evaluated by comparing Day 14 Cmax to Day 1 Cmax 
Rac(AUC) 
Accumulation ratio evaluated by comparing Day 14 AUCτ to Day 1 AUC0-24 
Parts B and C: MAD nonsmoker and smokerPhases, Various Days: 
Ctrough 
Observed concentration at the end of the dosing interval (predose 
concentrations on Days 2, 7, 11, 12, 13, and 14) 
The following PK parameters will be used for PK calculation and presented in the PK listings 
only 
Tlast 
Time of last measurable observed concentration 
Clast 
Observed concentration corresponding to Tlast  
λZ 
Apparent elimination rate constant, estimated by linear regression of the 
terminal linear portion of the log concentration versus time curve 
λZ Upper 
Upper limit on time for values included in the calculation of λz 
λZ Lower 
Lower limit on time for values included in the calculation of λz 
Number of Points 
Number of data points in computing λZ 
R2 
Goodness of fit for the terminal phase 
Residual area  
Extrapolated area (i.e., percentage of AUC0-∞ due to extrapolation from Tlast to 
infinity: [AUC0-∞ - AUC0-T]/ AUC0-∞*100) 
1 Sources: Gidal et al., 2017 and Boxenbaum et al., 1995 
7.5 
Pharmacokinetic Statistical Methodology 
All tables, figures and listings (TFLs), when appropriate, will be stratified by cohort and study 
day; for the food-effect cohort, additional stratification by meal condition will be performed. 
7.5.1 Summary Statistics 
Summary statistics of the individual concentration data and derived parameters will be calculated 
with Phoenix® WinNonlin® for the PK population. Summary statistics will be calculated for 
concentration at each individual time point and for all PK parameters.  


 
 
 
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Concentration data will be summarized by group using the following statistics: number of 
observations (N), arithmetic mean (mean), standard deviation (SD), minimum (min), median, 
maximum (max), and coefficient of variation (CV%). PK parameters will be summarized using 
these same statistics, as well as geometric mean and geometric mean CV%. 
7.5.2 Statistical Analysis 
Dose Proportionality 
For all study parts, appropriate dose–normalized PK parameters (Cmax and appropriate AUCs) 
will be assessed graphically for dose-proportionality (with Phoenix® WinNonlin®).  
Natural log-transformed PK parameters (Cmax and appropriate AUCs) will be assessed 
statistically for proportionality using SAS. Proportionality analysis will be done using a power 
model. The power model is defined as: 
ln(PK parameter) = α + β • ln(Dose) + ε 
where α is the intercept, β is the slope and ε is the error term. A linear model with ln-transformed 
dose as a continuous effect will be fitted. A point estimate and a 90% confidence interval will be 
derived for the slope (β).  
Dose proportionality may be assessed within different dose ranges if deemed appropriate with at 
least three doses. 
Food-Effect Assessment 
A statistical comparison will be performed in subjects enrolled in Cohort A3 to evaluate the 
effect of food on the PK of SBP-9330 with the natural logarithmic transformation of Cmax, 
AUC0-T, and AUC0-∞.  
Cmax, AUC0-T, and AUC0-∞ will be statistically analyzed using an Analysis of Variance 
(ANOVA) model. The fixed factors included in this model will be the Fed or Fasting condition, 
the period at which it was given (Day 1 or Day 8 [or Day 15]), as well as the sequence in which 
the treatment is under Fed or Fasting condition. A random factor is also added for the subject 
effect (nested within sequence). 
The 90% confidence interval for the exponential of the difference in least-squares (LS) means 
between the Fed and Fasting conditions will be calculated (Fed to Fasting ratio of geometric LS 
means).  
The formula to estimate the intra-subject coefficient of variation will be: 
, where MSE 
is the Mean Square Error obtained from the ANOVA model of the ln-transformed parameters. 
The parameter Tmax will be evaluated descriptively.  
Steady State  
Ctrough will be displayed graphically and summarized descriptively by day to assess for steady 
state. 
 
 
1

MSE
e


 
 
 
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7.5.3 Smoking Assessment (Part C only) 
The following data will be assessed for the Safety population of Part C and will be listed and 
summarized using descriptive statistics: 
 Expired carbon monoxide (ECO) level  
 Plasma cotinine level 
 Number of cigarettes smoked (smoking log) 
 
Minnesota Nicotine Withdrawal Scale (MNWS) responses 
 
Questionnaire on Smoking Urges – Brief version (QSU-Brief) responses 
 
 
Actual values and change from baseline will be presented in a listing and will be summarized by 
Symptoms (if applicable) and visit.  
 
 


 
 
 
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8 SAFETY ANALYSIS 
Unless otherwise specified, all available data will be listed and summary tables for safety 
assessments will be presented for the safety population as detailed in Table 8.   
Table 8: 
Data presentations for safety assessments  
Data 
Variables 
Presentation 
Adverse events 
Adverse event (AE) description, 
onset and resolution date and 
time, time from product use, 
severity, relationship to study 
drug, action taken, and outcome 
Listing (by subject, Cohort and treatment): 
L16.2.7.1 
Summary tables, including number and 
percentage of subjects experiencing: 
 
Reported AEs, 
 
Treatment-emergent adverse events 
(TEAEs), 
 
Drug-related TEAEs (i.e. those with 
a relationship classified as Definite, 
Probable, Possible and Unlikely),  
 
TEAEs by relationship to study 
treatment (i.e., Definite, Probable, 
Possible, Unlikely and Not related),  
 
TEAEs by severity,  
 
Serious TEAEs,  
 
Study drug-related serious TEAEs, 
 
TEAEs leading to withdrawal, and  
 
TEAEs with an outcome of death. 
Note: includes coded terms (system organ 
class [SOC] and preferred term [PT]) 
T14.3.1.1.1 – T14.3.1.4.4,  
T14.3.2.1  and T14.3.2.2 
Concomitant 
medications 
All medications taken during the 
study (as defined in the protocol 
and including prior medications 
that are continued), dose, units, 
frequency, formulation, route, 
indication/ reason taken, and date 
and time 
Listing 
Note: includes coded terms (anatomic 
therapeutic chemical [ATC] level 1 and 
preferred name) 
L16.2.7.2 
 
Extent of exposure 
Category of drug, treatment, total 
dose, dose unit, formulation, 
frequency, administration date and 
time, route of administration, Was 
the treatment administered as 
specified in the protocol? and 
dosing comments 
Listings: 
L16.2.5.1 
L16.2.5.2 
L16.2.5.3 
Clinical laboratory 
Laboratory results (refer to section Listings:  


 
 
 
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Data 
Variables 
Presentation 
evaluations 
9.2 for parameters) 
 All laboratory values by visit 
L16.2.8.1.1 – L16.2.8.1.7 
 All out-of-range laboratory values 
 All clinically significant laboratory values  
T14.3.4.1.1 – T14.3.4.1.2 
Summary tables 
 Summary of continuous tests 
 Summary of categorical tests 
T14.3.4.2.1 – T14.3.4.5.4 
Vital signs 
Blood pressure, pulse, respiratory 
rate and body temperature 
Listings:  
 All vital signs values 
L16.2.8.3.1 – 16.2.8.3.2 
 All out-of-range vital signs values  
 All clinically significant vital signs values 
T14.3.5.1.1 – T14.3.5.2.4Summary tables: 
 Summary of vital signs by visit  
T14.3.5.3.1 – T14.3.5.4.4 
Physical 
examination 
Physical examination findings 
Listings: 
 All Physical examination findings 
 L16.2.8.2All clinically significant 
Physical Examination findings 
T14.3.6.1 
Electrocardiograms 
(ECGs) 
ECG interpretations and findings 
Listings: 
 
all 12-Lead ECGs findings 
L16.2.8.4Summary tables: 
 
summary of ECG assessments by 
visit 
 
all out-of-range ECG values  
 
all clinically significant ECG values  
T14.3.7.1.1 – T14.3.7.1.2 
T14.3.7.2.1 – T14.3.7.2.4 
C-SSRS 
Columbia Suicide Severity Rating 
Scale 
Listing: 
L16.2.9.1 
 
Note: Sub-bullets denote individual listings or tables to be generated. 
8.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered an investigational product and which does not necessarily have a causal 
relationship with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including a clinically significant abnormal laboratory finding, for example), symptom, or 


 
 
 
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disease temporally associated with the use of an investigational product, whether or not related to 
the investigational product. 
Treatment emergent adverse events (TEAEs) are AEs not present prior to the exposure to study 
treatment or AEs already present that worsen in intensity or frequency following exposure to 
study treatment. All AEs reported following exposure to study treatment are considered TEAEs. 
All TEAEs will be assigned to a treatment using the following rules:  
 A TEAEs will be assigned to the last treatment taken by the subject where the date and 
time of the last treatment dosing is on or before of the start date and time of the event. 
Such assignment will be performed irrespective of any washout period between the 
start and stop dates of the TEAE.  
 Any TEAE started during the follow-up period will be assigned to the last treatment 
that the subject has taken.  
 In case that the time of onset or time of resolution is unknown, worst case scenario will 
be considered. For the onset, 00h01 will be the time considered. For the resolution 
time, if the time is unknown, 23h59 will be the time considered.  
Frequency tables summarizing all TEAEs and all study drug-related TEAEs (including SOC and 
PT) will be presented by Part A- SAD (Cohorts A1, A2, A4, A5, Pooled Placebo and Overall), 
Part A food-effect cohort (SBP-9330, Placebo and Overall), Part B – MAD (Cohorts B1, B2, B3, 
B4, Pooled Placebo and Overall) and Part C – Smoker (Cohorts C1, C2, C3, Pooled Placebo and 
Overall) as described in Table 8. 
All averse events will be presented in a listing as well, by study part, cohort, subject and 
treatment.  
8.2 
Clinical Laboratory Evaluations 
Laboratory data will be presented using units as reported by the clinical laboratory. 
The following clinical laboratory tests listed will be performed as scheduled in Appendix A. 
Clinical Laboratory Test 
Panel 
Description 
Clinical Chemistry: 
Alanine aminotransferase, albumin, alkaline phosphatase, bilirubin total, 
chloride, creatinine, glucose, potassium, carbon dioxide, calcium, uric 
acid, albumin, total bilirubin, lactate dehydrogenase, creatinine kinase, 
aspartate transaminase, amylase, lipase, and sodium 
Lipid profile: 
Total cholesterol, cholesterol high-density lipoprotein, cholesterol low-
density lipoprotein and triglycerides 


 
 
 
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Coagulation: 
Prothrombin time (PT)/INR and partial thromboplastin time (PTT) levels 
Endocrinology1: 
Follicle-stimulating hormone (for female subjects) 
Hematology: 
White cell count with differential (absolute values of neutrophil, 
lymphocyte, monocyte, eosinophil, and basophil), red cell count, 
hemoglobin, hematocrit, mean corpuscular volume, and platelet count 
Serology1: 
HIV-1/HIV-2 antibodies, hepatitis B surface antigen and 
hepatitis C virus antibody  
Urinalysis: 
Color, clarity, specific gravity, pH, leukocyte, protein, glucose, ketones, 
bilirubin, blood, nitrite, urobilinogen. Microscopic examination will only 
be performed if the dipstick test is outside of the reference range for 
leukocyte, blood, nitrite or protein 
Urine drug screen: 
Amphetamines, alcohol, barbiturates, benzodiazepines, cannabinoids, 
cocaine, cotinine, opiates and phencyclidine 
Pregnancy test: 
Serum pregnancy test at Screening only and urine pregnancy test for all 
other scheduled days 
 
Additional clinical laboratory tests may be performed by the medical laboratory as part of larger 
standard test panels (not required for subject safety). 
For hematology, chemistry and urinalysis, actual values and change from baseline will be 
presented in the listings and will be summarized by study part, laboratory test and visit. Values 
outside the normal range will be flagged in the listing. The results’ relationship to the reference 
range will be summarized by their status (Normal, Abnormal – Low, Abnormal – High) using 
frequencies and percentages. Frequency tables and percentages based on the number of subjects 
per visit will be used to summarize tests with categorical results. 
Subject listings of abnormal on-study laboratory values will be provided. Similarly, clinically 
significant on-study laboratory data will be presented in a second listing. 
8.3 
Vital Signs 
Vital signs will be measured as outlined in Appendix A.  
Vital signs to be measured are listed below.  
 Orthostatic systolic and diastolic BP and pulse rate  
 Body temperature  
                                              
 
 
 
 
 


 
 
 
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 Respiratory rate  
 
Blood pressure and pulse rate will be measured after the subject has been in the supine position for at 
least 5 minutes, repeat measurements will be taken after the subject has been standing in the upright 
position for at least 2 to 3 minutes (respiratory rate and temperature will be measured with blood 
pressure and pulse rate in the supine position only).  
When vital signs are scheduled at the same time as PK blood draws, the blood draws will be obtained 
at the scheduled time point and the vital signs will be obtained prior to the blood draw, as close as 
possible to the scheduled time point.  
On-study time points for vital sign measurements are presented in Table 9 (SAD Phase) and Table 
10 (MAD Phase). 
Table 9: Vital Sign Recording Schedule – SAD Phase 
Vital Sign Recording - Scheduled Time Points1 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) 
0.75, 1.25, 1.75, 3.75, 8, 11.75, and 23.25 hours post-dose (±15 minutes) 
Prior to discharge  
End of Study/Follow-up Visit 
1For the food-effect cohort, the vital signs assessments will be performed for each dosing 
Table 10: Vital Sign Recording Schedule – MAD and Smoker Phase 
Vital Sign Recording - Scheduled Time Points 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) 
1.75 hours post-dose (±15 minutes) on each dosing day  
3.5 hours post-dose (±15 minutes) on each dosing day1 
Prior to discharge 
End of Study/Follow-up Visit 
1. 
Time point applicable to Smoker Phase only. 
The normal range values for vital signs are as follows:  
 100 mmHg ≤ systolic blood pressure (BP) ≤ 140 mmHg in supine position. 
 60 mmHg ≤ diastolic BP ≤ 90 mmHg in supine position. 
 60 beats per minute (bpm) ≤ heart rate ≤ 100 bpm in supine position. 
 35.5 °C ≤ body temperature ≤ 37.5 °C. 
 10 breaths per minute ≤ respiratory rate ≤ 22 breaths per minute. 


 
 
 
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  ≥ 20 mmHg decrease in systolic BP from supine to standing. 
 ≥ 10 mmHg decrease in diastolic BP from supine to standing. 
 ≥ 30 bpm increase in heart rate from supine to standing. 
 
Actual values and change from baseline will be presented in a listing and will be summarized by 
study part, vital signs parameter, visit and time points. Values outside the reference range will be 
flagged in the listing. 
Subject listing of abnormal on-study vital signs values (Out-of-Range) will be provided. 
Similarly, clinically significant on-study vital signs values will be presented in a second listing. 
8.4 
Physical Examination Findings 
A physical examination will be performed by a medically qualified and licensed individual as 
outlined in Appendix A. 
The physical examination will include a general review of the following body systems (at 
minimum): general appearance, head, eye, ear, nose, throat, neck/thyroid, cardiovascular, 
respiratory, gastrointestinal, neurological, musculoskeletal/extremities, and skin. An abbreviated 
physical examination may be performed at the Investigator’s discretion upon admission or 
discharge from the clinical site. 
All physical examination records will be presented in a listing, by study part, cohort, subject,  
visit and category. Similarly, clinically significant physical examinations will be presented in a  
second listing. 
8.5 
12-Lead ECG Findings 
Triplicate 12-lead ECG (each performed approximately 1 minute apart) will be performed as outlined 
in Appendix A.  
On-study ECG measurements are specified in Table 11 (SAD Phase) and Table 12 (MAD Phase). 
Table 11: ECG Recording Schedule – SAD Phase 
ECG Recording - Scheduled Time Points1 
 Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) 
1, 3, 6, and 12 hours post-dose (±15 minutes) 
Prior to discharge  
End of Study/Follow-up Visit 
1For the food-effect cohort, the vital signs assessments will be performed for each dosing 


 
 
 
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Table 12: ECG Recording Schedule – MAD and Smoker Phase 
ECG Recording - Scheduled Time Point 
Upon admission (check-in) 
Prior to dosing (within 60 minutes of dosing) on Day 1 only 
3 hours post-dose (±15 minutes) on each dosing day  
Prior to discharge 
End of Study/Follow-up Visit 
 
Mean values will be used for triplicate ECG results in summary tables. Actual values and change 
from baseline will be presented in a listing and will be summarized by study part, 12-Lead ECG 
parameter, visit and time point. Values outside the reference range will be flagged in a listing. 
The 12-Lead ECG parameters and overall assessments (Normal, NCS, or Abnormal – CS) will 
be presented in a listing.  
Subject listings of abnormal on-study ECG assessments (Abnormal – NCS or Abnormal – CS)  
will be provided. Similarly, clinically significant on-study 12-Lead ECG assessments (Abnormal 
– CS) will be presented in a second listing. 
8.6 
Columbia Suicide Severity Rating Scale (C-SSRS) 
The C-SSRS is a questionnaire designed for the assessment of suicidal ideation and behavior in 
adolescents and adults. This will include events in the last 2 years prior to Screening.  
To monitor for the emergence of suicidal ideation and behavior, subjects will undergo C-SSRS 
evaluations at the time points indicated in Appendix A. 
On-study C-SSRS should be completed upon admission, upon discharge (each admission and 
discharge for Cohort A3 [Food-Effect Cohort]) and the EOS/Follow-up visit. 
If a subject becomes suicidal during the study as per the results of the C-SSRS questionnaire, an 
Investigator should provide the appropriate treatment to the subject. 
Listing will be presented for C-SSRS data.  
 
 
 


 
 
 
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9 DATA HANDLING AND PRESENTATION 
All safety and statistical outputs will be generated using SAS software, version 9.4. 
Pharmacokinetic outputs will be generated using WinNonlin version 8.0. 
All programs used to generate statistical analyses will be validated according to standard 
operating procedures (SOPs) of Altasciences.  
The analyses described in this plan are considered a priori, in that they have been defined prior to 
database lock and/or prior to breaking the blind.  Any analyses performed subsequent to database 
lock and/or breaking the blind that are not described within the present plan will be considered 
post hoc and exploratory.  Post hoc analyses will be labeled as such in the corresponding 
statistical output and identified in the clinical study report (CSR). 
9.1 
Safety Analysis Presentation 
Adverse events and medical history will be classified using the Medical Dictionary for 
Regulatory Activities (MedDRA) terminology version 24.0 as defined in the study data 
management plan (DMP).  
Prior and concomitant medications will be coded with the World Health Organization Drug 
Dictionary- Enhanced (WHO-DDE) March 2021 as defined in the study DMP. 
In general, all safety summary tables will be presented for the safety population. Summaries will 
be presented for each study part as below: 
 Part A- SAD (Cohorts A1, A2, A3 fasted, A4, A5, Pooled Placebo and Overall) 
 Part A food-effect cohort (SBP-9330, Placebo and Overall)  
 Part B – MAD (Cohorts B1, B2, B3, B4, Pooled Placebo and Overall) 
 Part C -  Smoker (Cohorts C1, C2, C3, Pooled Placebo and Overall) 
In general, the data listings will include all enrolled subjects up to the point of study completion 
or discontinuation; exceptions will be listings pertaining to a subset of subjects only (e.g., 
subjects with protocol deviations) or a subset of records/events (e.g., abnormal laboratory 
values). 
Categorical variables will be summarized using the PROC FREQ procedure. Continuous 
variables will be summarized using the PROC UNIVARIATE procedure. For natural log (ln)-
transformed endpoints, geometric mean, geometric standard deviation (SD), and coefficient of 
variation (CV%) will also be presented. 
The following general comments also apply to all statistical analyses and data presentations: 
 Duration variables will be calculated using the general formula: (end date - start date) +1. 
 If the reported value of a clinical laboratory parameter cannot be used in a statistical 
summary table (e.g., a character string is reported for a parameter of the numerical type), 
a coded value must be appropriately determined and used in the statistical analyses.  In 
general, a value or lower and upper limit of normal range such as ‘<10’ or ‘≤5’ will be 
treated as ‘10’ or ‘5’ respectively, and a value such as ‘>100’ will be treated as ’100’.  
However, the actual values as reported in the database will be presented in data listings. 


 
 
 
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 When assessments are repeated for a given time point or performed at unscheduled times, 
only the result which is the closest to the dosing time will be included in summary tables. 
In general, summary statistics for raw variables (i.e., variables measured at the study site or 
central laboratory) will be displayed as follows:  
 Minima and maxima will be displayed to the same number of decimal places as the raw 
data.  
 Means, medians, and quartiles will be displayed to 1 additional decimal place.  
 Standard deviations will be displayed to 2 additional decimal places.   
 Percentages will be displayed to 1 decimal place. Percentages between 0 and 0.1 
(exclusive) will be displayed as ‘<0.1’.   
 P-values will be displayed to 3 decimal places. P-values that are less than 0.001 will be 
displayed as ‘<0.001’. 
The numbers of decimal places for summary statistics of derived variables (i.e., variables that are 
not measured by the study site but are calculated for analysis based on other measured variables) 
will be determined on a case-by-case basis.  In general:  
 Minima and maxima will be displayed to the commonly used unit of precision for the 
parameter.  
 Means, medians, quartiles, and confidence limits will be displayed to 1 additional 
decimal place.  
 Standard deviations will be displayed to 2 additional decimal places.  
9.2 
Pharmacokinetic Analysis Presentation 
In general, all PK summary tables will be presented for the PK population. 
Individual raw PK concentrations will be displayed with the same precision as received from the 
bioanalytical laboratory. 
Precision for individual PK parameters will be displayed as follows:  
 Concentration-related PK parameters (e.g., Cmax, AUCs) will be displayed to 3 significant 
figures, 
 Clearance and volume of distribution will be displayed with 3 significant figures, 
 Parameters associated with time (e.g. Tmax and Thalf) will be displayed with 2 decimal 
places, 
 Percentages will be displayed with 2 decimal places, 
 R2 and λz will be displayed with 4 decimal places. 
Summary statistics for concentration and PK parameters will be displayed with the same 
precision as the individual values, with the exception of number of observations (N) and CV% 
which will be presented with 0 and 1 decimal place, respectively. 


 
 
 
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9.3 
Analysis Timepoints  
Unless otherwise specified, the baseline value will be defined as the last non-missing evaluation 
prior to the first dose of study medication. 
9.4 
Methods for Handling Missing Data  
No imputations of values for missing data (i.e, blank, “Not Done”, “Not Applicable”, etc) will be 
performed and data presentations will reflect the data point as it appears in the case report form 
(CRF) or electronic data file.  
 
 


 
 
 
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10 INTERIM ANALYSES AND DATA SAFETY MONITORING 
Preliminary blinded “top line” PK results will be generated after each cohort of the SAD and 
MAD phase for dose selection and safety assessment prior to the next dose escalation.  
These preliminary blinded PK results will be performed on SBP-9330 data as outlined in 
Sections 7.1 through 7.4, with the exception that nominal times will be used in the analysis 
instead of actual times. Blinded concentration tables, mean and blinded individual plasma 
concentration-time profiles, blinded PK parameter tables of the key PK endpoints (e.g., Cmax, 
Tmax, and AUCs) will be generated, data permitting. 
 
 


 
 
 
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11 CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
No changes from the protocol-specified analyses are planned. 
 
 


 
 
 
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12 GENERAL INFORMATION RELATED TO DATA PRESENTATIONS 
The formats and layouts of TFLs are provided in a separate document and are common displays.  
Their numbering and general content follow the International Conference on Harmonisation 
(ICH) E3 guidelines.  Actual formats and layouts may be altered slightly from those presented as 
necessary to accommodate actual data or statistics.  Minor format changes will not require 
updates to the SAP, rather they may be documented in a Note to SAP. 
 
 


 
 
 
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APPENDIX A STUDY SCHEDULE(S) 
Table 13: Schedule of Activities – Part A (SAD Phase with Nested Food-Effect Cohort) 
 
Assessment Period1  
 
Visit2 
Screening 
Pretreatment 
Treatment 
Follow-up/ End of 
Study3 
Study Day 
-28 to -2 
-1 
1 
(Predose) 
1 
2 
3 
8±1 
Confinement 
 
X 
X 
X 
X 
X 
 
Ambulatory 
X 
 
 
 
 
 
X 
Admission 
 
X 
 
 
 
 
 
Discharge 
 
 
 
 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
Eligibility Check 
X 
X 
X 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Physical Examination 
X 
X4 
 
 
 
X4 
X 
Body Weight and Height (Including BMI 
Calculation) 
X 
X5 
 
 
 
 
 
Serology (HBsAg, HCVAb, anti-HIV 
1 and 2) 
X 
 
 
 
 
 
 
Urine Drug and Alcohol Screen6 
X 
X 
 
 
 
 
 
FSH (postmenopausal females only) 
X 
 
 
 
 
 
 
Pregnancy Test (Females Only)7 
X 
X 
 
 
 
 
X 
Clinical Laboratory Tests6,8 
X 
X 
X 
 
 
X 
X 
12-lead ECG9,10 
X 
X 
X 
X 
 
X 
X 
Vital Signs10,11 
X 
X 
X 
X 
X 
X 
X 
C-SSRS Questionnaire12 
X 
X 
 
 
 
X 
X 
M.I.N.I. 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
Study Drug Administration 
 
 
 
X 
 
 
 
Blood Sampling for PK10,13 
 
 
X 
X 
X 
X 
 
Previous and Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 


 
 
 
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Assessment Period1  
 
Visit2 
Screening 
Pretreatment 
Treatment 
Follow-up/ End of 
Study3 
Study Day 
-28 to -2 
-1 
1 
(Predose) 
1 
2 
3 
8±1 
Adverse Event Monitoring 
 
X 
X 
X 
X 
X 
X 
Abbreviations: BMI = body mass index; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; 
FSH = follicle-stimulating hormone; HBsAg = hepatitis B surface antigen; HCVAb=hepatitis C virus antibody; HIV = human immunodeficiency 
virus; M.I.N.I. = Mini International Neuropsychiatric Interview; P K= pharmacokinetic; SAD = single ascending dose;  
1 
Subjects will be in the clinic from Day -1 until 48 hours (Day 3) post-dose. Subjects will return for follow-up/EOS assessments on Day 8±1. 
Subjects for the fed period of the food-effect cohort (Cohort A3) should report to the clinic after the washout period (at least 7 to 14 days after 
fasting dose) and repeat the 8-day SAD schedule of assessments beginning on Day -1. 
2 
The timing, type, and number of safety and PK assessments may be updated depending on emerging safety and PK data. 
3 
Subjects who discontinue the study early should complete the EOS procedures. Subjects in SAD cohorts A1, A2, A4, and A5 should return to 
the clinic for follow-up at Day 8±1; subjects in the food-effect 2-period cohort (Cohort A3) should return to the clinic for follow-up at Day 
8±1 in Period 2 (5 days after the last PK blood sample in fed part). 
4 
An abbreviated physical examination may be performed at the Investigator’s discretion upon admission and discharge from the clinical site. 
5 
Weight only. 
6 
Refer to Appendix 6 for more details. 
7 
Serum pregnancy test for all female subjects at Screening and urine pregnancy test, for female subjects of childbearing potential only, at all 
other timepoints. 
8 
Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): at Screening; on Day -1 
(admission) and at pre-dose, 48 hours post-dose; and at follow-up/EOS. 
9 
Triplicate 12-lead ECG: at Screening; Day -1 (admission), at pre-dose (within 60 minutes of dosing) and at 1, 3, 6, and 12 hours post-dose 
(±15 minutes); prior to discharge, and at follow-up/EOS. 
10 
When safety and PK blood draws coincide, procedures should be carried out in the following order: (1) ECGs, (2) vital signs, (3) PK blood 
sampling (nominal). 
11 
Vital signs: Screening; Day -1 (admission); at pre-dose (within 60 minutes of dosing) and at 0.75, 1.25, 1.75, 3.75, 8, 11.75, and 23.25 hours 
post-dose (±15 minutes); prior to discharge; and at follow-up/EOS. Orthostatic measurements will be obtained at Screening, Day -1, pre-dose, 
and at 1.75 hours (±15 minutes) post dose.  For orthostatic measurements blood pressure and pulse rate will be measured after the subject has 
been in the supine position for at least 5 minutes, repeat measurements will be taken after the subject has been standing in the upright position 
for at least 2 to 3 minutes (respiratory rate and temperature will be measured with blood pressure and pulse rate in the supine position only). 
12 
A baseline/screening version of the C-SSRS will be used at Screening and a “since-last-visit” version will be used at all subsequent visits 
where the C-SSRS is administered. 
13 
Blood sampling for PK of SBP-9330 in plasma: at pre-dose (within 60 minutes of dosing) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 
48 hours post-dose (±10%). 
 


 
 
 
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Table 14: Schedule of Activities – Part B (MAD Phase) 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Follow-up/ 
End of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 
21±1 
Confinement 
 
X 
X 
X X X X X X X X X X X X X X X X 
 
Ambulatory2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
X 
Body Weight and Height 
(Including BMI Calculation) 
X 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (HBsAg, HCVAb, 
anti-HIV 1 and 2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug and Alcohol Screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test (Females Only)6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical Laboratory Test5,7 
X 
X 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
12-lead ECG8,9 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Vital Signs9,10 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Eligibility Check 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
 
 
X X X X X X X X X X X X X X 
 
 
 
Blood Sampling for PK9,11 
 
 
X 
X X 
 
 
 
 
X 
 
 
 
X X X X X X 
 
C-SSRS Questionnaire12 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
M.I.N.I. 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and Concomitant 
Medication 
X 
X 
X 
X X X X X X X X X X X X X X X X 
X 


 
 
 
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Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Follow-up/ 
End of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 
9 10 11 12 13 14 15 16 
21±1 
Adverse Event Monitoring 
 
X 
X 
X X X X X X X X X X X X X X X X 
X 
Abbreviations: BMI = body mass index; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS = end of study; FSH = follicle-
stimulating hormone; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibody; HIV = human immunodeficiency virus; MAD = multiple 
ascending dose; M.I.N.I. = Mini International Neuropsychiatric Interview; PK = pharmacokinetic 
1 
The timing, type, and number of safety, and PK assessments may be updated depending on emerging safety and PK data. 
2 
Subjects who discontinue the study early should complete the EOS procedures. 
3 
An abbreviated physical examination may be performed at the Investigator’s discretion upon admission or discharge from the clinical site. 
4 
Weight only. 
5 
Refer to Appendix 6 for more details. 
 
6 
Serum pregnancy test for all female subjects at Screening and urine pregnancy test, for female subjects of childbearing potential only, at all other 
timepoints. 
7 
Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): at Screening; on Day -1 (admission); at pre-
dose on Days 1, 3, 7, 14, and 16; and at follow-up/EOS. 
8 
Triplicate 12-lead ECG: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) on Day 1 and at 3 hours post-dose on each dosing day (i.e., 
Days 1 to 14) (±15 minutes); prior to discharge; and at follow-up/EOS. 
9 
When safety and PK blood draws coincide, procedures should be carried out in the following order: (1) ECGs, (2) v ital signs, (3) PK blood sampling 
(nominal). 
10 
Vital signs: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) and 1.75 hours post-dose on each dosing day (i.e., Days 1 to 14) (±15 
minutes); prior to discharge; and at follow-up/EOS. Orthostatic measurements will be obtained at Screening, Day -1, pre-dose, and at 1.75 hours 
(±15 minutes) post dose.  For orthostatic measurements blood pressure and pulse rate will be measured after the subject has been in the supine position 
for at least 5 minutes, repeat measurements will be taken after the subject has been standing in the upright position for at least 2 to 3 minut es (respiratory 
rate and temperature will be measured with blood pressure and pulse rate in the supine position only). 
11 
Blood sampling for PK of SBP-9330 in plasma: at pre-dose (within 60 minutes of dosing); at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose 
(±10%) on Day 1; within 60 minutes prior to morning drug administration on Day 7, 11, 12, and 13; and within 60 minutes prior to drug administration 
and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 48 hours post-dose on Day 14 (±10%). 
12 
A baseline/screening version of the C-SSRS will be used at Screening and a “since-last-visit” version will be used at all subsequent visits where the 
C-SSRS is administered. 
 
 
 


 
 
 
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Table 15: Schedule of Activities – Part C (Smoker Phase) 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Followup/ End 
of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 9 10 11 12 13 14 15 16 
21±1 
Confinement 
 
X 
X 
X X X X X X X X X X X X X X X 
X 
 
Ambulatory2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Smoking History 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X3 
X 
Body Weight and Height 
(Including BMI Calculation) 
X 
X4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (HBsAg, HCVAb, 
antiHIV 1 and 2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug and Alcohol Screen5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FSH (postmenopausal females 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test (Females Only)6 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Clinical Laboratory Test5,7 
X 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
12-lead ECG8,9 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Vital Signs9,10 
X 
X 
X 
X X X X X X X X X X X X X X 
 
X 
X 
Eligibility Check 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Administration 
 
 
 
X X X X X X X X X X X X X X 
 
 
 
Blood Sampling for PK9,11 
 
 
X 
X X 
 
 
 
 
X 
 
 
 
X X X X X 
X 
 
Expired CO Level12 
X 
X 
X 
X X X X X X X X X X X X X X 
 
 
 
Blood Sampling for Cotinine13 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
Smoking Log 
 
X 
 
X X X X X X X X X X X X X X X 
 
 


 
 
 
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Page 46 of 47 
 
Assessment Period  
 
Visit1 
Screening Pretreatment 
Treatment 
Followup/ End 
of Study2 
Study Day 
-28 to -2 
-1 
1 
(Predose) 1 
2 
3 
4 
5 
6 
7 
8 9 10 11 12 13 14 15 16 
21±1 
FTCD 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking TLFB 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MNWS 
 
X 
 
X X X X X X X X X X X X X X 
 
 
 
QSU-Brief 
 
X 
 
X X X X X X X X X X X X X X 
 
 
 
C-SSRS Questionnaire14 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
M.I.N.I. 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and Concomitant 
Medication 
X 
X 
X 
X X X X X X X X X X X X X X X 
X 
X 
Adverse Event Monitoring 
 
X 
X 
X X X X X X X X X X X X X X X 
X 
X 
Abbreviations: BMI = body mass index; C-SSRS = Columbia-Suicide Severity Rating Scale; CO = carbon monoxide; ECG = 
electrocardiogram; EOS = end of study; FSH = follicle-stimulating hormone; FTCD = Fagerström Test for Cigarette Dependence; 
HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibody; HIV = human immunodeficiency virus; MAD = multiple 
ascending dose; M.I.N.I. = Mini International Neuropsychiatric Interview; MNWS = Modified Minnesota Nicotine Withdrawal Scale; 
PK = pharmacokinetic; QSU-Brief = Questionnaire on Smoking Urges – Brief version; TLFB = Smoking Time-Line Follow-back 
1. The timing, type, and number of safety, and PK assessments may be updated depending on emerging safety and PK data. 
2.Subjects who discontinue the study early should complete the EOS procedures. 
3.An abbreviated physical examination may be performed at the Investigator’s discretion upon admission or discharge from the clinical site. 
4.Weight only. 


 
 
 
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5. See APPENDIX 6 from protocol for details. 
6. Serum pregnancy test for all female subjects at Screening and urine pregnancy test, for female subjects of childbearing potential only, at all other timepoints. 
7. Clinical laboratory tests (including clinical chemistry, lipid profile, coagulation, hematology, and urinalysis): at Screening; on Day -1 (admission); at pre-
dose on Days 1, 3, 7, 14, and 16; and at follow-up/EOS. 
8. Triplicate 12-lead ECG: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) on Day 1 and at 3 hours post-dose on each dosing day (i.e., Days 1 
to 14) (±15 minutes); prior to discharge; and at follow-up/EOS. 
9. When safety and PK blood draws coincide, procedures should be carried out in the following order: (1) ECGs, (2) vital signs, (3) PK blood sampling 
(nominal), (4) smoking assessments. 
10. Vital signs: at Screening; Day -1 (admission); at pre-dose (within 60 minutes) and 1.75 hours post-dose on each dosing day (i.e., Days 1 to 14) 
(±15 minutes); prior to discharge; and at follow-up/EOS. Orthostatic measurements will be obtained at Screening, Day -1, pre-dose, 1.75 hours (±15 minutes), 
and 3.5 hours (±15 minutes) post dose.  For orthostatic measurements blood pressure and pulse rate will be measured after the subject has been in the supine 
position for at least 5 minutes, repeat measurements will be taken after the subject has been standing in the upright position for at leas t 2 to 3 minutes 
(respiratory rate and temperature will be measured with blood pressure and pulse rate in the supine position only ). 
11. Blood sampling for PK of SBP-9330 in plasma: at pre-dose (within 60 minutes of dosing); at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours post-dose 
(±10%) on Day 1; within 60 minutes prior to morning drug administration on Day 7, 11, 12, and 13; and within 60 minutes prior to drug administration and at 
0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36, and 48 hours post-dose on Day 14 (±10%). 
12. Expired breath CO will be measured with a Bedfont Smokerlyzer™. 
13. Cotinine samples should be collected within 60-minutes prior to dosing on dosing days. 
14. A baseline/screening version of the C-SSRS will be used at Screening and a “since-last-visit” version will be used at all subsequent visits where the C-SSRS 
is administered.