Clinical trial NCT02672111
Conditions: Opioid Use Disorder
Sponsor: Braeburn Pharmaceuticals
Start date: 2015-11-01; Completion date: 2017-05-01
Enrollment: 228 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Open-label multi-center, 48 week safety study, consistent with standard practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up.

Detailed description:
Open-label multi-center, 48 week safety study, consistent with standard practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up.

Patients who are currently taking sublingual (SL) BPN (weekly or monthly prescription visits) or individuals who are actively seeking BPN treatment but who have not yet begun a treatment regimen, may be eligible for the study.

Following Screening, qualified subjects meeting inclusion criteria and not meeting exclusion criteria will be initiated on either CAM2038 q1w or q4w, based on their current treatment status (qualified subjects currently on SL BPN or seeking BPN treatment). Qualified subjects will be initiated or transitioned to CAM2038 q1w or q4w as follows:

Initiation of BPN treatment - initiate with CAM2038 q1w

Currently receiving SL BPN treatments - transfer to corresponding CAM2038 q1w or q4w dose

Arms: arm 1: CAM2038 (buprenorphine FluidCrystal®)

Subjects previously exposed to SL BPN/NX who received CAM2038 q1w or q4w arm 2: CAM2038 (buprenorphine FluidCrystal®) New to BPN Treatment who received CAM2038r q1w or q4w
Interventions: intervention 1: CAM2038 q1w or q4w exposure to SL BPN/NX intervention 2: CAM2038 q1w or q4w new to BPN treatment
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_001.pdf: 
Clinical Trial Protocol 
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Clinical Trial Protocol  
HS-14-499 
An Open-Label Multicenter Study Assessing the Long-Term 
Safety of a Once-Weekly and Once-Monthly, Long-Acting 
Subcutaneous Injection Depot of Buprenorphine 
(CAM2038) in Adult Outpatients with Opioid Use Disorder 
CAM2038 50 mg/mL q1w (buprenorphine FluidCrystal® once-weekly 
subcutaneous injection depot) 
CAM2038 356 mg/mL q4w (buprenorphine FluidCrystal® once-monthly 
subcutaneous injection depot) 
EUDRACT 2015-003035-35 
IND 114082 
Original Protocol: v1.0, 29-Jul-2015 
Global Protocol Amendment 1: v2.0, 21-Dec-2015 
Global Protocol Amendment 2: v3.0, 12-Jul-2016 
Global Protocol Amendment 3: v4.0, 18-Nov-2016 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
BRAEBURN PHARMACEUTICALS:  
47 Hulfish Street, Suite 441 
Princeton, NJ 08542 
CONFIDENTIAL 
This protocol is the property of Braeburn Pharmaceuticals and is intended solely for the 
guidance of the clinical investigation. This protocol may not—in full or part—be passed on, 
reproduced, published, or distributed to any person or entity who is not bound by written 
confidentiality agreement, for any purpose, without the prior consent of Braeburn 
Pharmaceuticals. 


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1. 
SPONSOR AND KEY PERSONNEL CONTACT INFORMATION 
ROLE IN STUDY  
NAME 
 CONTACT INFORMATION 
Study Sponsor 
Braeburn 
Pharmaceuticals, Inc. 
47 Hulfish Street, Suite 441 
Princeton, NJ  08542 
 
Medical Monitor(s) 
Dr. Jamal Gasmi, MD, 
PhD 
MedPace CRO 
Medical Director 
Tel: +33 147 729 882 
Fax: +33 927 369 787 
E-mail: j.gasmi@medpace.com 
Sponsor Project Manager 
Sonia Oosman, MS 
 
Braeburn Pharmaceuticals 
Director, Clinical Operations 
47 Hulfish Street, Suite 441 
Princeton, NJ 08542 
Tel: 609-436-9636 
E-mail: 
sonia@braeburnpharma.com 
 
Coordinating Investigator 
Sonnie Kim, Pharm.D. 
 
Braeburn Pharmaceuticals 
VP, Clinical Development & 
Medical Affairs 
47 Hulfish Street, Suite 441 
Princeton, NJ 08542 
Tel: 301-332-6767 
Email: 
sonnie@braeburnpharma.com 
 
 


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2. 
PROTOCOL SYNOPSIS 
Name of Sponsor/Company: Braeburn Pharmaceuticals 
Name of Investigational Products:  
CAM2038 q1w (buprenorphine FluidCrystal® once-weekly injection depot) 
CAM2038 q4w (buprenorphine FluidCrystal® once-monthly injection depot) 
Name of Active Ingredient: Buprenorphine  
Study Title: 
An Open-Label, Multicenter Study Assessing the Long-Term Safety of a Once-Weekly and 
Once-Monthly Long-Acting Subcutaneous Injection Depot of Buprenorphine (CAM2038) in Adult 
Outpatients with Opioid Use Disorder 
Objectives: 
Primary Objective: 
To demonstrate the safety and tolerability of CAM2038 products in 12-month (48-week) buprenorphine 
(BPN) treatment in adult outpatients with opioid use disorder. 
Secondary Objectives: 
To evaluate efficacy of CAM2038 through several efficacy parameters, including urine toxicology, signs 
and symptoms of withdrawal and cravings in adult outpatients with opioid use disorder. 
Methodology: 
This is an open-label multi-center, 12-month safety study, consistent with standard practice for long-term 
safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once 
monthly) and will have 3 phases: Screening, Treatment, and Follow-up.   
Patients who are currently taking sublingual (SL) BPN (weekly or monthly prescription visits) or 
individuals who are actively seeking BPN treatment but who have not yet begun a treatment regimen, 
may be eligible for the study.  
Following Screening, qualified subjects meeting inclusion criteria and not meeting exclusion criteria will 
be initiated on either CAM2038 q1w or q4w, based on their current treatment status (qualified subjects 
currently on SL BPN or seeking BPN treatment).  
Qualified subjects will be initiated or transitioned to CAM2038 q1w or q4w as follows: 
§ 
Initiation of BPN treatment – initiate with CAM2038 q1w  
§ 
Currently receiving SL BPN treatments – transfer to corresponding CAM2038 q1w or q4w dose 
Subjects will be allowed to receive supplemental BPN during the study with booster SC injections of 
CAM2038 q1w 8 mg at the discretion of the Investigator. Dose adjustments (up or down titrations) will 
also be allowed at scheduled visits. 
The study will end when at least 100 subjects have been exposed to CAM2038 for 12 months (48 weeks). 
All subjects will be transitioned back to usual care and followed for an additional 4 weeks (up to 
Week 52). 
To ensure adequate enrollment and address potential inconvenience to subjects, all subjects will receive 
appropriate compensation for time and travel expenses related to attendance at study visits. All costs of 
medications and counseling will also be covered.  


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Name of Sponsor/Company: Braeburn Pharmaceuticals 
Name of Investigational Products:  
CAM2038 q1w (buprenorphine FluidCrystal® once-weekly injection depot) 
CAM2038 q4w (buprenorphine FluidCrystal® once-monthly injection depot) 
Name of Active Ingredient: Buprenorphine  
Number of Subjects (Planned):  
The study will enroll approximately 228 subjects (new entrants to CAM2038 treatment) with estimated 
dropout rate of approximately 50% to ensure at least 100 subjects are exposed to CAM2038 for up to 48 
weeks. The study will end after at least 100 subjects have been exposed to CAM2038 for 48 weeks. 
Diagnosis and Main Criteria for Inclusion: 
This study will enroll adult outpatients with opioid use disorder as defined by the Diagnostic and 
Statistical Manual of Mental Disorders – Fifth Edition (DSM-V).  
Subjects must meet one of the following criteria for BPN treatment history: 
a. Voluntarily seeking treatment for opioid use disorder (not currently on BPN treatment for 
at least last 60 days but seeking BPN treatment), or; 
b. Currently on SL BPN treatment  
Investigational Product, Dosage and Mode of Administration: 
CAM2038 q1w: buprenorphine FluidCrystal® subcutaneous (SC) injection depot for once weekly 
administration) (50 mg/mL) at doses of 8, 16, 24 and 32 mg (buprenorphine base) (0.16, 0.32, 0.48 or 
0.64 mL SC injection). 
CAM2038 q4w: buprenorphine FluidCrystal® SC injection depot for once monthly administration 
(356 mg/mL) at doses of 64, 96, 128 or 160 mg (buprenorphine base) (0.18, 0.27, 0.36 or 0.45 mL SC 
injection). 
Reference Therapy, Dosage and Mode of Administration: 
This is an open-label study, no reference therapy (placebo or active comparator) will be administered. 
Duration of Study: 
This is a 12-month (48-week) treatment study. Subject with no previous exposure to CAM2038 will 
receive treatment for up 48 weeks.  


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Name of Sponsor/Company: Braeburn Pharmaceuticals 
Name of Investigational Products:  
CAM2038 q1w (buprenorphine FluidCrystal® once-weekly injection depot) 
CAM2038 q4w (buprenorphine FluidCrystal® once-monthly injection depot) 
Name of Active Ingredient: Buprenorphine  
Criteria for Evaluation: 
Safety Endpoints: 
§ 
Adverse events (AEs) and serious adverse events (SAEs) 
§ 
Clinical laboratory tests 
§ 
Electrocardiogram (ECG) 
§ 
Vital signs 
§ 
Physical and injection site examinations 
§ 
Concomitant medications 
Efficacy Measures: 
§ 
Urine toxicology results for illicit opioids  
§ 
Self-reported illicit opioid use  
§ 
Retention (%) in treatment 
§ 
Work Productivity and Activity Impairment Questionnaire-General Health (WPAI-GH) 
§ 
EQ-5D-5L Health Questionnaire 
§ 
Patient Satisfaction Scale 
§ 
Measures of opioid withdrawal:  
o Clinical Opiate Withdrawal Scale (COWS) 
o Subjective Opiate Withdrawal Scale (SOWS) 
§ 
Measures of opioid craving: 
o Desire to Use visual analogue scale (VAS)  
o Need to Use VAS 
§ 
Urine toxicology results for other drugs of abuse 
Statistical Methods (Data Analysis): 
Two safety populations will be considered: the Full Exposure Safety population and the Overall Safety 
Population. The Full Exposure Safety Population will include all subjects who have been exposed to 
CAM2038 for 48 weeks. The Overall Safety Population will include all subjects who received at least one 
CAM2038 treatment. Exposure and safety summaries will be presented for both populations. 
Adverse events will be coded by primary system organ class (SOC) and preferred term according to the 
Medical Dictionary for Regulatory Activities (MedDRA), and summarized by number and percent of 
subjects in each primary SOC and preferred term. Summaries of these AE subsets will be presented for 
relationship to study drug, intensity, seriousness, AEs or SAEs leading to discontinuation and AEs 
occurring in 5% or greater of any treatment group (by preferred term). Frequencies for deaths and 


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Name of Sponsor/Company: Braeburn Pharmaceuticals 
Name of Investigational Products:  
CAM2038 q1w (buprenorphine FluidCrystal® once-weekly injection depot) 
CAM2038 q4w (buprenorphine FluidCrystal® once-monthly injection depot) 
Name of Active Ingredient: Buprenorphine  
hospitalizations will also be summarized. 
Data for clinical laboratory tests, ECG, vital signs, and physical and injection site examinations will be 
summarized using standard descriptive and change from baseline statistics. Shift tables and tabular 
summaries of abnormalities will be provided, where appropriate. Medications will be coded using the 
World Health Organization Drug dictionary and summarized using descriptive statistics.  
By-subject listings will be provided for all safety data. 
Exploratory efficacy measures will be summarized by visit using standardized descriptive statistics and 
listed by subject. 
 


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3. 
TABLE OF CONTENTS 
1. Sponsor and Key Personnel Contact Information ....................................................... 2 
2. Protocol Synopsis ............................................................................................................ 3 
3. Table of Contents ............................................................................................................ 7 
4. List of Abbreviations and Definition of Terms ........................................................... 10 
5. introduction ................................................................................................................... 12 
5.1. 
Background .............................................................................................................. 12 
5.1.1. CAM2038 q1w (Once Weekly) .............................................................................. 12 
5.1.2. CAM2038 q4w (Once Monthly) ............................................................................ 13 
5.2. 
Study Rationale ........................................................................................................ 14 
5.3. 
Dosing Rationale ...................................................................................................... 15 
5.4. 
Overall Risk Benefit Assessment ............................................................................. 19 
6. Study objectives ............................................................................................................ 21 
6.1. 
Primary Objective .................................................................................................... 21 
6.2. 
Secondary Objective ................................................................................................ 21 
7. Investigational Plan ...................................................................................................... 22 
7.1. 
Overall Study Design and Plan ................................................................................ 22 
7.1.1. Screening Visit (Week -3 to Week -1): ................................................................... 24 
7.1.2. Treatment Phase (Week 1 to Week 48) ................................................................... 24 
7.1.3. Follow-up Phase (Week 49 to 53): ......................................................................... 26 
7.2. 
Discussion of Study Design ..................................................................................... 27 
7.3. 
Selection of Study Population .................................................................................. 27 
7.4. 
Inclusion Criteria ...................................................................................................... 27 
7.5. 
Exclusion Criteria ..................................................................................................... 27 
7.6. 
Removal of Subjects from Therapy or Assessment ................................................. 29 
8. Treatments ..................................................................................................................... 30 
8.1. 
Treatment Administration ........................................................................................ 30 
8.2. 
Identity of Investigational Product(s) ....................................................................... 31 
8.2.1. Handling, Storage, and Accountability .................................................................. 31 
8.2.2. Dispensing and Administration .............................................................................. 32 
8.2.3. Sublingual Buprenorphine/Naloxone ..................................................................... 32 
8.3. 
Method of Assigning Subjects to Treatment Groups ............................................... 32 
8.4. 
Selection of Doses .................................................................................................... 32 
8.5. 
Selection and Timing of Dose .................................................................................. 33 
8.6. 
Blinding .................................................................................................................... 33 


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8.7. 
Prior and Concomitant Therapy ............................................................................... 33 
9. Study Procedures and Assessments ............................................................................. 35 
9.1. 
Demographics and Other Baseline Characteristics .................................................. 39 
9.1.1. Informed Consent ................................................................................................... 39 
9.1.2. Demographics ......................................................................................................... 39 
9.1.3. Medical History ...................................................................................................... 39 
9.1.4. Medication History ................................................................................................. 39 
9.1.5. Substance Use and Treatment History ................................................................... 39 
9.1.6. Contraceptive Requirements .................................................................................. 39 
9.2. 
Eligibility Review .................................................................................................... 40 
9.3. 
Efficacy Assessments ............................................................................................... 40 
9.3.1. Urine Toxicology for Opioids ................................................................................ 40 
9.3.2. Self-Reported Illicit Drug Use ............................................................................... 41 
9.3.3. Measures of Desire and Need to Use ..................................................................... 41 
9.3.4. Quality of Life Questionnaires and Patient Satisfaction Scale .............................. 41 
9.3.5. Measures of Withdrawal ......................................................................................... 42 
9.3.6. Urine Toxicology for Other Drugs of Abuse .......................................................... 42 
9.3.7. Unscheduled Visits, Medication and Counseling ................................................... 42 
9.4. 
Safety Assessments .................................................................................................. 42 
9.4.1. Adverse Events and Serious Adverse Events ......................................................... 42 
9.4.2. Pregnancy ............................................................................................................... 45 
9.4.3. Clinical Laboratory Assessments ........................................................................... 46 
9.4.4. Vital Signs .............................................................................................................. 48 
9.4.5. 12-Lead Electrocardiogram (ECG) ........................................................................ 48 
9.4.6. Physical Examination ............................................................................................. 48 
9.4.7. C-SSRS ................................................................................................................... 48 
9.4.8. Injection Site Examination ..................................................................................... 49 
9.4.9. Psychosocial Counseling ........................................................................................ 49 
9.4.10. Treatment Identification Card ................................................................................ 49 
9.4.11. Other Safety Considerations ................................................................................... 49 
9.5. 
Appropriateness of Measures ................................................................................... 49 
9.6. 
Safety Variables ........................................................................................................ 50 
9.7. 
Efficacy Variables ..................................................................................................... 50 
10. Data Quality Assurance ................................................................................................ 51 
10.1. Data Collection ......................................................................................................... 51 
10.2. Study Auditing and Monitoring ............................................................................... 51 
11. Statistical Methods and Determination of Sample Size ............................................ 53 
11.1. Statistical and Analytical Plans ................................................................................ 53 
11.2. Analysis Populations ................................................................................................ 53 


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11.3. Planned Analyses ..................................................................................................... 53 
11.3.1. Demographics and Other Baseline Characteristics ................................................ 53 
11.3.2. Analysis of Efficacy Measures ............................................................................... 53 
11.3.3. Analysis of Safety Assessments ............................................................................. 53 
11.4. Determination of Sample Size ................................................................................. 54 
12. Study Administration and Investigator Responsibilities ........................................... 55 
12.1. Regulatory and Ethical Considerations .................................................................... 55 
12.1.1. Ethical Conduct of the Study ................................................................................. 55 
12.1.2. Ethics Approval ...................................................................................................... 55 
12.1.3. Subject Informed Consent ...................................................................................... 55 
12.2. Privacy and Confidentiality ...................................................................................... 56 
12.3. Study and Site Closure ............................................................................................. 56 
12.4. Regulatory Documents and Records Retention ....................................................... 57 
12.5. Delegation of Responsibilities and Adequate Resources ......................................... 57 
12.6. Protocol Amendments .............................................................................................. 58 
12.7. Financial Disclosure ................................................................................................. 58 
13. Sponsor Approval Page ................................................................................................ 59 
14. Investigator Protocol Agreement Page ........................................................................ 60 
15. References ...................................................................................................................... 61 
 
Table of Tables 
Table 1: Plasma Concentrations of Buprenorphine (Geometric Mean) After Single 
Subcutaneous Administration of CAM2038 q1w to Healthy Subjects 
Under Naltrexone Blockage ..................................................................... 18 
Table 2: Doses of CAM2038 q1w and q4w for Subjects Transitioning from SL 
BPN/BPX .................................................................................................. 30 
Table 3: Schedule of Assessments ........................................................................................ 36 
Table 4: Clinical Laboratory Assessments ............................................................................ 47 
 
Table of Figures 
Figure 1: Observed and Predicted Plasma Concentration Versus Time Profiles for 
CAM2038 ................................................................................................. 17 
Figure 2: Predicted Plasma Concentration Versus Time Profiles For CAM2038 ................. 17 
Figure 3: Predicted Plasma Concentration Versus Time Profiles For CAM2038 ................. 18 
Figure 4: Overview of Study Design .................................................................................... 23 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
Adverse event 
AIDS 
Acquired Immune Deficiency Syndrome  
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BPN 
Buprenorphine 
BPX 
Buprenorphine/naloxone 
CFR 
Code of Federal Regulations 
Cmax 
Maximum plasma concentration 
Cmin 
Minimum plasma concentration 
CNS 
Central nervous system 
COWS 
Clinical Opioid Withdrawal Scale 
CRF 
Case Report Form (may include electronic data capture systems or paper forms) 
CS 
Clinically significant 
CSA 
Clinical Study Agreement 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
Ctrough 
Concentration levels prior to next injection 
DSM-V 
Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
FC 
FluidCrystal® 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Institutional Ethics Committee 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IV 
Intravenous  
MedDRA 
Medical Dictionary of Regulatory Activities 
MOP 
Manual of Procedures 
NCS 
Not clinically significant 
PAC-SYM 
Patient Assessment of Constipation Symptoms 
PT 
Prothrombin time 
RBC 
Red blood cell 


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SAE 
Serious adverse event  
SC 
Subcutaneous 
SL 
Sublingual 
SOC 
System Organ Class 
SOWS 
Subjective Opioid Withdrawal Scale 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
US 
United States 


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5. 
INTRODUCTION 
5.1. 
Background 
Buprenorphine (BPN) is an opioid with mixed agonist-antagonist properties, and together with 
appropriate counseling and psychotherapy, has been shown to be effective in the treatment of 
opioid dependence. Treatment with BPN has been demonstrated to significantly reduce opioid-
positive urines, i.e., to reduce illicit drug use, and increase retention of patients in outpatient 
treatment programs (Johnson et al, 1992; Strain et al, 1994; Schottenfeld et al, 1997; Ling et al, 
1998). 
CAM2038 (buprenorphine FluidCrystal® [FC] subcutaneous [SC] injection depot) once weekly 
(hereafter referred to as CAM2038 q1w) and once monthly (q4w) (hereafter referred to as 
CAM2038 q4w) are ready-to-use, extended release BPN products developed for opioid 
dependence treatment with a target of once weekly or once monthly SC dosing posology, 
respectively.  
CAM2038 q1w and q4w were developed using the proprietary lipid-based and ambient 
responsive FC Injection depot technology. The principle behind the FC Injection depot is a 
liquid-to-gel phase transition, occurring immediately as the lipid based FC system is exposed to 
in vivo conditions of SC tissue. The phase transition proceeds from the outside towards the 
center of the injected FC by absorption of minute quantities of water. Thus, injection of 
CAM2038 q1w and q4w into SC tissue results in an immediate and spontaneous formation of 
controlled BPN release matrix providing long-acting release in vivo with a minimum initial burst 
release. The dual nature of the FC system, i.e., a true liquid drug product in vitro before injection 
and stable gel in vivo after injection, enables a ready-to-use drug product in a prefilled syringe. 
CAM2038 q1w and q4w are designed for convenient and safe SC injection using a prefilled 
syringe (from 0.15 to 0.6 mL volume depending on dose and product) including a needle safety 
device and with no need for mixing or temperature adjustment prior to administration. In 
addition, the injection volumes for CAM2038 q1w and q4w are relatively low and can be 
administered using a fine gauge needle (23 G). Overall, these ready-to-use, long-acting 
CAM2038 depots have been designed with a focus of enabling easy administration, dosing 
flexibility, and importantly, minimizing risks of misuse, diversion and poor patient compliance.  
5.1.1. 
CAM2038 q1w (Once Weekly) 
Subcutaneous CAM2038 q1w has so far been investigated after single and repeated doses in 3 
clinical trials, in both patients and healthy volunteers. An initial study assessed 
pharmacokinetics, pharmacodynamics and safety in opioid dependent patients (Study HS-07-
307). Study HS-07-307 results also showed that CAM2038 q1w was well tolerated, both locally 
and systemically. Importantly, no treatment emergent serious adverse events (SAEs) were 
observed and drug-related local tolerability findings were limited to 4 of 42 patients (9.5%). 
Three patients experienced mild injection site pain and 1 patient exhibited transient injection site 
inflammation (mild) and injection site pruritus (moderate). Two additional clinical studies were 
subsequently performed in healthy volunteers (under naltrexone blockade) to assess the 


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pharmacokinetics and bioavailability of single and repeat doses of CAM2038 q1w versus 
repeated doses of sublingual (SL) BPN (i.e., at steady state) and single dose of intravenous (IV) 
BPN (Studies HS-11-426 and HS-13-487). These two studies demonstrated that after 
administration of the studied doses of CAM2038 q1w, the plasma concentrations corresponded 
to those obtained after administration of SL BPN at approved doses. The BPN levels after 
administration of CAM2038 q1w were furthermore similar in healthy volunteers and patients 
with opioid dependence. The systemic tolerability of CAM2038 q1w was good in both studies 
and similar to the reference IV and SL BPN products. Local tolerability in Study HS-11-426 
(Nsafety=60) was very good with no adverse events (AEs) attributed to injection site tolerability. 
Similarly, local tolerability of CAM2038 q1w was very good in Study HS-13-487, featuring 4 
repeated SC injections of CAM2038 q1w into the buttock site (1 subject reported 1 AE of 
injection site pain).   
Based on these studies, the following main conclusions were drawn regarding clinical properties 
of CAM2038 q1w:  
• Extended BPN release over one week at target plasma concentrations   
• Dose proportionality and flexible/multiple dosing options 
• 6- to 8-fold higher bioavailability versus SL BPN 
• BPN plasma concentrations over 7 days within ranges of those produced by 
corresponding SL BPN doses at steady-state (i.e., approved 8 mg, 16 mg, or 24 mg 
doses), supporting dose selection for this Phase III study 
• Observed and predicted (repeated dose), Caverage and Ctrough values for CAM2038 q1w 
within therapeutic plasma levels 
• Repeated-dose administration demonstrated time-independent pharmacokinetics  
• Good safety and systemic tolerability in patients  
• Safety in healthy volunteers comparable to reference IV and SL BPN treatments  
• Good local tolerability in patients and healthy volunteers 
The clinical pharmacokinetic profile and good systemic and local tolerability of CAM2038 q1w 
evidenced in subjects in these 3 studies is also supported by a large body of data generated in 
non-clinical pharmacokinetic and toxicology studies in the dog, minipig and rat of single and 
repeat SC doses of CAM2038 q1w, including repeat weekly doses of the FC vehicle formulation 
for 6-months. In summary, nonclinical data have indicated no systemic toxicity associated with 
CAM2038 q1w or the FC injection depot vehicle. Subcutaneous administration of CAM2038 
q1w has been shown to be well tolerated both systemically and locally in single and repeat dose 
non-clinical studies in the rat and in the dog. The treatment-related findings have been limited to 
clinical observations in agreement with and considered related to known pharmacological effects 
of the drug substance BPN, and to reversible, local inflammatory reactions at the SC site of 
injection. The latter findings were similar to the physiological response to a foreign body. The 
FC related injection site findings appeared to be reversible and self-limiting, and only apparent at 
the immediate vicinity of test article deposition. 
5.1.2. 
CAM2038 q4w (Once Monthly) 
Subcutaneous CAM2038 q4w has been investigated after single administration in the bridging 
clinical pharmacokinetic study in healthy volunteers versus repeated dose CAM2038 q1w (i.e., at 
steady state), repeated dose SL BPN (i.e., at steady state), and single dose of intravenous (IV) 


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BPN (Study HS-13-487). The following conclusions can be drawn regarding the clinical 
properties of CAM2038 q4w:  
• Extended BPN release over 4 weeks at target plasma concentrations 
• Dose proportionality was shown within the dosage interval of 64 to 192 mg CAM2038 
q4w   
• 6- to 8-fold higher bioavailability than SL BPN, comparable to CAM2038 q1w 
• Observed BPN plasma concentrations over 4 weeks comparable to CAM2038 q1w over 
one week, and to SL BPN over 24 hours at steady-state (i.e., for approved 8 mg, 16 mg, 
or 24 mg doses), supporting dose selection for this Phase III study 
• Predicted Css,av and Css,trough values for 64, 96 and 128 mg CAM2038 q4w similar to 
CAM2038 q1w and SL BPN (i.e., for approved 8 mg, 16 mg, or 24 mg doses) 
• Safety profile comparable to reference IV and SL BPN treatments  
• Good local tolerability 
The most commonly reported drug-related AEs after CAM2038 q1w and CAM2038 q4w 
administration to the healthy volunteers under naltrexone blockade in the study were nausea 
(63% of subjects), dizziness (54% of subjects) and vomiting (39% of subjects). The local 
tolerability was good with 6 subjects experiencing 7 AEs that were assessed as related to 
CAM2038 q4w (injection site reactions, injection site pain, injection site induration and 
application site bruise). Two SAEs were reported by 2 subjects after treatment with 192 mg 
CAM2038 q4w. The first SAE was an event of withdrawal reaction and the second SAE was an 
event of dehydration due to nausea and vomiting. Both SAEs were assessed as related to 
CAM2038 q4w (withdrawal reaction was also assessed as related to the concomitant treatment 
with naltrexone) and the event of withdrawal reaction qualified for reporting as a suspected 
unexpected serious adverse reaction (SUSAR). There were no deaths or any other significant 
AEs and most of the AEs were mild and transient. Analysis of clinical chemistry, hematology 
and urinalysis parameters did not suggest any significant safety issues for CAM2038 q4w. 
The non-clinical assessment of CAM2038 q4w and the FC vehicle, supported by publically 
available data for the drug substance buprenorphine and for the components of the vehicle, 
suggests safe use of CAM2038 q4w for the proposed clinical development. This conclusion is 
further supported by results from non-clinical and clinical studies of the once weekly product, 
CAM2038 q1w, comprising the same active substance and functional lipid components.   
Additional information about CAM2038 can be found in the current version of the Investigator’s 
Brochure. 
5.2. 
Study Rationale 
Opioid drug dependence is a major health and social issue and is often a chronic medical 
condition that requires long-term maintenance treatment. An important aim of the treatment 
programs for opioid drug dependence is to enable the patients to become abstinent. Further 
important aims are to improve their mental and physical health, as well as their social conditions. 
This can be achieved by increasing patients’ quality of life and reducing the burden on the 
society and relatives. Moreover, opioid people often inject with used syringes and needles, and 


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thus expose themselves to high risk of transmission of infectious diseases, including HIV and 
hepatitis C.  
Opioid maintenance treatment, such as SL BPN, is one of the most effective treatment options 
available for opioid dependent drug users and is associated with substantial reductions in deaths, 
and HIV transmission (WHO, 2004).  However, because patients often discontinue treatment 
prematurely, an outcome associated with higher rates of relapse to drug use, treatment strategies 
that aim to keep patients in treatment longer and/or improve patient adherence may have 
additional advantages (Chandler et al, 2009).  While daily dosing with SL BPN has proven 
effective, the need for daily administration of treatment may negatively influence patients’ 
compliance. Moreover, SL tablets or film can be easily diverted for illicit use, injected for greater 
effect, or accidentally ingested, especially by children (Chandler et al, 2009; Winstock et al, 
2008). The limitations associated with SL BPN are of particular relevance to patients who have 
children at home, to those who have difficulty making frequent visits to the physician’s office 
(e.g., patients in remote locations, those with limited mobility, or those who travel frequently) or 
to those who have difficulty managing the responsibility of daily dosing.  
CAM2038 q1w and q4w may increase patient compliance relative to daily SL BPN dosage 
forms, and may help prevent treatment noncompliance in higher-risk patients (i.e., those patients 
who take “drug holidays” from their BPN when they wish to abuse illicit opioids). In addition, 
CAM2038 q1w and q4w may provide significant potential for reducing risks of diversion, abuse, 
and accidental pediatric exposure, which continue to be important public health consequences of 
SL BPN therapy.  
In animal repeat-dose toxicity studies, CAM2038 q1w or FC vehicle formulation have been 
administered weekly for up to 6-months with no systemic toxicity associated with 
CAM2038 q1w or the FC injection depot vehicle observed. However, the long-term safety 
profiles of CAM2038 q1w and q4w in humans have not been described. In Study HS-13-487, 
pharmacokinetic profiles were evaluated for 4 repeat doses of CAM2038 q1w (one SC injection 
per week for 4 weeks) and one dose of CAM2038 q4w. In an upcoming parallel Phase III safety 
and efficacy study (HS-11-421), CAM2038 q1w and CAM2038 q4w will each be administered 
for up to 12 weeks (3 months). Therefore, the purpose of this study is to demonstrate the long-
term safety of CAM2038 (q1w and q4w) as an office-based therapy for opioid maintenance 
treatment with BPN in patients with opioid use disorder. 
5.3. 
Dosing Rationale 
The weekly subcutaneous CAM2038 q1w product has so far been investigated after single and 
repeated doses in three separate clinical trials, in both patients and healthy volunteers. An initial 
study assessed pharmacokinetics, pharmacodynamics and safety in opioid dependent patients 
(Study HS-07-307). Following FDA’s advice at the pre-IND meeting (PIND 114,082), two 
additional clinical studies were subsequently performed in healthy volunteers to assess the 
pharmacokinetics and bioavailability of CAM2038 q1w versus repeated doses of sublingual (SL) 
BPN (i.e., at steady state) and single dose of intravenous (IV) BPN (Studies HS-11-426 and 
HS-13-487). The total number of subjects exposed to CAM2038 q1w in these studies was 114.  


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Subcutaneous CAM2038 q4w has been investigated in one bridging clinical pharmacokinetic 
study in healthy volunteers versus repeat dose CAM2038 q1w, repeat dose SL BPN (i.e., at 
steady state), and single dose of intravenous (IV) BPN (Study HS-13-487). The total number of 
exposed subjects in this study was 79, with 62 subjects receiving CAM2038 q4w.   
During the induction, stabilization, and as needed for maintenance treatments, subcutaneous 
doses of 8 to 32 mg CAM2038 q1w will be provided based on the clinical needs of the patients. 
This dose range is expected to cover the needs of patients that are currently eligible to SL BPN 
treatment. This assumption is based on the head-to-head comparison of BPN exposures of 
CAM2038 q1w versus SL BPN (Subutex®), which were assessed in the HS-11-426 and HS-13-
487 Phase 1 trials. Occasionally, an SC booster injection of 8 mg CAM2038 q1w may be needed 
on top of the weekly dose of 32 mg. For maintenance treatment with CAM2038 q4w, the 
corresponding planned dose range is 64 mg to 160 mg.  
Figures below demonstrate observed and predicted BPN plasma concentrations for different dose 
combinations of CAM2038 q1w, CAM2038 q4w and Subutex® over 28 days. These data 
demonstrate that observed and predicted plasma concentrations of CAM2038 q1w over one week 
and CAM2038 q4w over one month are comparable to SL BPN over 24 hours at steady-state 
(i.e., for approved 8 mg, 16 mg, or 24 mg doses), thus supporting doses selected for the Phase III 
studies.  
Figures below are geometric mean observed steady state Cmax and Ctrough for Subutex from HS-
11-426 and HS-13-487; Predicted plasma concentration versus time profiles for CAM2038 q1w 
from single and repeat dose data in HS-13-487; Observed steady state plasma concentration 
versus time profiles for CAM2038 q1w 16 mg from HS-13-487; and Predicted steady state 
plasma concentration versus time profiles for CAM2038 q4w from single-dose data in HS-13-
487. 


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Figure 1: Observed and Predicted Plasma Concentration Versus Time Profiles for 
CAM2038 
 
Figure 2: Predicted Plasma Concentration Versus Time Profiles For CAM2038 
 
 
0.1
1
10
100
0
7
14
21
28
Ctrough for SL Subutex 8 mg at steady state
Cmax for SL Subutex 8 mg at steady state
SC CAM2038 q1w 16 mg pred 
SC CAM2038 q1w 16 mg obs
SC CAM2038 q4w 64 mg pred 
Plasma BPN conc (ng/mL)
Time (days)
0.1
1
10
100
0
7
14
21
28
Ctrough for SL Subutex 16 mg at steady state
Cmax for SL Subutex 16 mg at steady state
SC CAM2038 q1w 24 mg pred 
SC CAM2038 q4w 96 mg pred 
Plasma BPN conc (ng/mL)
Time (days)


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Figure 3: Predicted Plasma Concentration Versus Time Profiles For CAM2038 
 
The following table demonstrates the estimation of plasma buprenorphine levels during the 
induction treatment with CAM2038 q1w.  These plasma levels provide a rationale that induction 
treatment with CAM2038 q1w may mimic the gradual increase in the plasma buprenorphine 
levels provided with titration methods with SL BPN. 
Table 1: Plasma Concentrations of Buprenorphine (Geometric Mean) After Single 
Subcutaneous Administration of CAM2038 q1w to Healthy Subjects Under 
Naltrexone Blockage 
Time after dose 
(h) 
Plasma concentrations of buprenorphine (ng/mL) 
CAM2038 q1w 8 mg 
CAM2038 q1w 16 
mg 
CAM2038 q1w 32 
mg 
Pre-dose 
<0.025 
<0.025 
<0.025 
0.5 
0.0759 
0.253 
0.220 
1 
0.119 
0.396 
0.391 
2 
0.257 
0.722 
0.748 
4 
0.568 
1.39 
1.83 
6 
0.767 
1.63 
2.61 
10 
1.40 
2.84 
4.42 
0.1
1
10
100
0
7
14
21
28
Ctrough for SL Subutex 24 mg at steady state
Cmax for SL Subutex 24 mg at steady state
SC CAM2038 q1w 32 mg pred 
SC CAM2038 q4w 128 mg pred 
Plasma BPN conc (ng/mL)
Time (days)


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24 
1.65 
2.84 
5.00 
36 
1.11 
2.02 
3.76 
 
 
5.4. 
Overall Risk Benefit Assessment 
BPN is a substance with well-established use in the treatment dependence on opioid drugs. The 
CAM2038 products contain BPN in a new FluidCrystal (FC) formulation for subcutaneous (SC) 
injection. Clinical trials have demonstrated effectiveness of BPN in reducing illicit opioid use 
and improving retention rates of patients in outpatient maintenance treatment of opioid 
dependence, as well as substantial reduction in criminal activity, deaths, and HIV transmission. 
The need for daily administration of SL BPN may negatively influence patients’ compliance and 
BPN tablets or film can be easily diverted for illicit use, injected for greater effect, or 
accidentally ingested, especially by children. 
CAM2038 q1w and CAM2038 q4w are ready-to-use, SC BPN FC Injection depots that are being 
developed as alternative dosage form for treatment of opioid drug dependence by providing 
extended BPN release at target plasma concentrations over the weekly and monthly dosing 
intervals, respectively. Due to the fact that CAM2038 products need to be administered by a 
clinician, CAM2038 products cannot be abused or diverted by patients. In addition, it may 
decrease the tendency for patients to request unnecessarily high BPN doses. It will also ensure 
that the dose required is the dose received. Compared with the sublingual buprenorphine 
products on the market, CAM2038 q1w and CAM2038 q4w have several potential advantages: 
1) rapid therapeutic onset (with maximum plasma concentrations established within 24 hours 
after injection) followed by steady long-acting release; 2) reduced variation in buprenorphine 
plasma levels over time (stable plasma levels attained for at least 28 days (CAM2038 q4w) and 7 
days (CAM2038 q1w) resulting in more consistent therapeutic plasma levels and a possible 
reduction in morning “cravings”; 3) less frequent dosing resulting in reduced frequency of clinic 
visits and need for medical support; 4) significantly higher bioavailability, meaning less drug 
substance in circulation and on the street; 5) decreased risk of drug diversion; and 6) easier dose 
adjustment. 
To date, three Phase I/II clinical studies (HS-07-307, HS-11-426 and HS-13-487) have been 
conducted in both opioid dependent and healthy volunteers under naltrexone block.  The safety 
profile of CAM2038 q1w and CAM2038 q4w is comparable to reference SL BPN approved 
treatment and good local tolerability was demonstrated with findings limited to only a few cases 
of transient, mild, local inflammation, pruritus and/or injection site pain. 
A number of potential AEs can be associated with the administration of long-acting depots. The 
most severe side-effects specific for the investigational product that may occur are related to 
local reactions at the site of injection after subcutaneous administration and include dermal 
ulcers or necrotic wounds at the injection site. Additional potential AEs include over-dose of 
buprenorphine and allergy to buprenorphine. There is also a potential risk of local obstruction 
and blockage at the injection site with accidental intravascular injection 


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Systemic repeated toxicity for up to 4 months of once-weekly SC administration of CAM2038 
q1w, once weekly and CAM2038 q4w, once-every-4-week administration in dogs showed 
absence of systemic toxicity by assessment of complete clinical pathology, histopathology and 
toxicokinetics (TK). The treatment related findings were limited to reversible clinical effects 
compatible with known pharmacological effects of BPN (reduced activity, ataxia, sporadic 
salivation, and intermittent soft faeces, as well as reduction in body weight and food 
consumption) and to local, transient injection site findings, characterised as foreign body 
response. No novel toxicological aspects arose for BPN in the CAM2038 drug product 
formulations in comparison with available information on the drug substance alone. Absence of 
systemic toxicity has also been shown for up to chronic SC exposure of the FC system in rodents 
and non-rodents. The local toxicity findings at the injection site following SC administration of 
the CAM2038 drug products in a large number of non-clinical studies were described by 
necropsies and histopathology as a reversible local continuum of an inflammatory response 
consistent with the physiological inflammatory reactions occurring in response to the injection of 
an insoluble material.         
The current protocol is intended to demonstrate the long-term 12-month safety of CAM2038 
q1w and q4w for the treatment of opioid dependence.  The safety monitoring practices employed 
by this protocol are adequate to protect the patients’ safety and should detect all expected 
treatment-emergent AEs (TEAEs).  
 
The volume of blood removed from the subject is approximately 30 mL over the course of the 
entire study (Screening to Follow-up, but does not include repeat or additional tests ordered by 
the Investigator). This volume presents no undue risk to the subjects.  
 
Therefore, CAM2038 q1w and q4w may provide alternative treatment options that potentially 
can increase patient compliance relative to daily SL BPN dosage forms, and may help prevent 
treatment noncompliance in higher-risk patients (i.e., those patients who take “drug holidays” 
from their BPN when they wish to abuse illicit opioids). In addition, CAM2038 q1w and q4w 
may provide significant potential for reducing risks of diversion, abuse, and accidental pediatric 
exposure, which continue to be important public health consequences of SL BPN therapy.  
In addition an indirect health benefit to the patients enrolled in this trial is the free medical tests 
received during the study.  
The available information suggests that the present clinical study has a favorable risk-benefit 
ratio.  
 
 


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6. 
STUDY OBJECTIVES 
 
6.1. 
Primary Objective 
The primary objective of the study is:  
§ To demonstrate the safety and tolerability of CAM2038 products in 12-month (48-week) 
BPN treatment in adult outpatients with opioid use disorder. 
6.2. 
Secondary Objective 
The secondary objective of the study is:  
§ To evaluate efficacy of CAM2038 through several efficacy parameters, including urine 
toxicology, signs and symptoms of withdrawal and cravings in adult outpatients with 
opioid use disorder. 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design and Plan 
This is an open-label multi-center, 12-month (48-week) safety study, consistent with standard 
practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once 
weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up.   
Patients who are currently taking SL BPN (weekly or monthly prescription visits) or those 
individuals who are actively seeking BPN treatment but who have not yet begun a treatment 
regimen may be eligible for the study.  
Following Screening, qualified subjects meeting inclusion criteria and not meeting exclusion 
criteria will be initiated on either CAM2038 q1w or q4w, based on their current treatment status 
(qualified subjects currently on SL BPN or seeking BPN treatment).  
Qualified subjects will be initiated or transitioned to CAM2038 q1w or q4w as follows: 
§ Initiation of BPN treatment – initiate with CAM2038 q1w  
§ Currently on SL BPN treatments – transfer to corresponding CAM2038 q1w or q4w dose 
Subjects will be allowed to receive temporary dose adjustments during the study with rescue 
booster SC injections of CAM2038 q1w 8 mg, at the discretion of the Investigator. Dose 
adjustments will also be allowed at scheduled visits. 
During the Treatment Phase, subjects will receive CAM2038 treatment for up to 48 weeks. The 
study will end when at least 100 subjects have been exposed to CAM2038 for 12 months 
(48 weeks). All subjects will be transitioned back to usual care and followed for an additional 
4 weeks (up to Week 53). 
To ensure adequate enrollment and address potential inconvenience to subjects, all subjects will 
receive appropriate compensation for time and travel expenses related to attendance at study 
visits. All costs of medications and counseling will also be covered.  
Germany only: The subject management procedures in the study comply with the statutory 
requirements in the German Verordnung über das Verschreiben, die Abgabe und den Nachweis 
des Verbleibs von Betäubungsmitteln (Betäubungsmittel-Verschreibungsverordnung – BtMVV, 
last amended 15 July 2009) and the drug substitution processes comply with German Richtlinien 
der Bundesärztekammer zur Durchführung der substitutionsgestützten Behandlung 
Opiatabhängiger (19 February 2010). 
The overall study design is illustrated in Figure 4. 
Section 9 provides additional information on the baseline, safety, and efficacy assessments 
included in the study. Study endpoints are described in Section 9.6 and Section 9.7. Statistical 
analysis is described in Section 11. 


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Figure 4: Overview of Study Design 
 
 
BPN=buprenorphine; SL=sublingual. 
Note: Subjects in the CAM2038 q1w once weekly group may be transferred to CAM2038 q4w once monthly at any 
time during the study at the Investigator’s discretion, using the guidance provided in Section 7.1.2.3.  


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7.1.1. 
Screening Visit (Week -3 to Week -1):  
Medical and eligibility screening will occur within 1-3 weeks of the Treatment Phase (Day 1). At 
Screening, subjects will provide written informed consent to participate in the study before any 
protocol-specified procedures or assessments are completed. The Screening Visit will include 
standard medical screening procedures, complete medical/psychosocial history, urine toxicology 
and detailed substance use and treatment history, as outlined in Table 3. 
7.1.2. 
Treatment Phase (Week 1 to Week 48) 
7.1.2.1. 
Day 1 (Week 1) (CAM2038 q1w) 
New entrants to BPN Treatment:  On Day 1, for subjects who are not currently receiving SL 
BPN or buprenorphine/naloxone (SL BPN/BPX), treatment will be initiated with CAM2038 
q1w in the following manner: 
Day 1: On Day 1, subjects will receive the following, while on site:  
§ A 4 mg SL BPN tablet test dose and observed for at least 1 hour prior to study drug 
administration. 
§ Once tolerability is confirmed (i.e., no precipitated withdrawal symptoms), a single 
CAM2028 q1w (once-weekly) 16 mg injection (0.32 mL of active) will be administered. 
 
Day 2:  All subjects will return to the clinic on Day 2 to ensure tolerability. 
Day 4: All subjects will return to the clinic. Subjects who return on Day 4 still experiencing 
withdrawal symptoms should receive a single CAM2038 q1w 8 mg SC injection (0.16 mL of 
active). A visit window of                
 ±1 day is allowed for the Day 4 visit.  
Days 5 to 7: Subjects requiring additional dosage adjustments may return to the clinic on Days 5 
to 7 if needed, based on withdrawal symptoms or tolerability. Subjects who require additional 
increases in dose will receive up to two additional CAM2038 q1w 8 mg SC injections (0.16 mL 
of active) (i.e., up to a maximum of 40 mg SC injection dose per week). 
 
Subjects Currently on Weekly BPN Treatment: Subjects who are currently receiving SL 
BPN/BPX and are considered a candidate for CAM2038 q1w treatment by the Investigator will 
be transitioned to CAM2038 q1w in the following manner: 
§ Subjects will receive a single CAM2038 q1w SC injection that corresponds to their 
current SL BPN/BPX dose prior to Day 1: 
o ≤  6 mg SL BPN/BPX:   8 mg (0.16 mL) CAM2038 q1w SC injection 
o 8-10 mg SL BPN/BPX:  16 mg (0.32 mL) CAM2038 q1w SC injection 
o 12-16 mg SL BPN/BPX:  24 mg (0.48 mL) CAM2038 q1w SC injection 
o 18-24 mg SL BPN/BPX:  32 mg (0.64 mL) CAM2038 q1w SC injection 


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§ Subjects may return to the clinic for additional titration with CAM2038 q1w (8 mg SC 
booster injections), as needed, up to a maximum weekly dose of 40 mg per week. 
Subjects should not take their ordinary SL BPN tablet(s) on Day 1 (i.e., the last dose of SL BPN 
should be taken on the day before dosing with CAM2038 q1w). 
Subjects will return to the clinic for weekly visits during which they will receive their CAM2038 
q1w SC injection treatments.  
7.1.2.2. 
Day 1 (Week 1) (CAM2038 q4w) 
Subjects Currently on Monthly BPN Treatment: Subjects who are currently receiving SL 
BPN/BPX and are considered a candidate for CAM2038 q4w treatment by the Investigator may 
be transitioned to CAM2038 q4w in the following manner: 
§ Subjects will receive a single CAM2038 q4w SC injection that corresponds to their 
current SL BPN/BPX dose prior to Day 1: 
o 8-10 mg SL BPN/BPX:  64 mg (0.18 mL) CAM2038 q4w SC injection 
o 12-16 mg SL BPN/BPX:  96 mg (0.27 mL) CAM2038 q4w SC injection 
o 18-24 mg SL BPN/BPX:  128 mg (0.36 mL) CAM2038 q4w SC injection 
o 26-32 mg SL BPN/BPX:  160 mg (0.45 mL) CAM2038 q4w SC injection 
Subjects should not take their ordinary SL BPN tablet(s) on Day 1 (i.e., the last dose of SL BPN 
should be taken on the day before dosing with CAM2038 q4w). 
7.1.2.3. 
Treatment Visits (Weeks 2 to 48) 
Subjects will return to clinic for visits based on each subject’s dose of CAM2038 (q1w – once 
weekly or q4w – once monthly). 
Subjects receiving CAM2038 q1w will return to the clinic weekly to receive their next dose and 
for safety and other assessments as outlined in Table 3. At the discretion of the Investigator, 
subjects may receive dose adjustments during the scheduled CAM2038 q1w weekly dose visits 
(up to a maximum weekly dose of 40 mg per week). 
Subjects may return to the clinic for additional titration with CAM2038 q1w (8 mg SC booster 
injections) as needed (i.e., at unscheduled visits), up to a maximum weekly dose of 40 mg per 
week. 
At any weekly visit, the Investigator may transition subjects from weekly (CAM2038 q1w) to 
monthly (CAM2038 q4w) clinic visits after, at the minimum, taking the following criteria into 
consideration on the day of the visit where the transition of dose will occur (ie. Prior to new dose 
administration): 
§ Subject is on a stable dose of CAM2038 q1w without any additional fluctuations in dose 
for 4 weeks 
§ Subject has minimal subjective and no objective withdrawal symptoms, based on the 
SOWS and COWS scores (SOWS ≤7 and COWS ≤5). 
§ Subject exhibits diminished desire/need to use, based on VAS scores. 


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§ Subject has diminished use of illicit opioids, according to the Investigator’s discretion  
Subjects who are eligible for transitioning from CAM2038 q1w to CAM2038 q4w will be 
transitioned in the following manner: 
§ Subjects will receive a single CAM2038 q4w SC injection, using the following 
conversion guidelines: 
o 16 mg (0.32 mL) CAM2038 q1w:  64 mg (0.18 mL) CAM2038 q4w 
o 24 mg (0.48 mL) CAM2038 q1w:  96 mg (0.27 mL) CAM2038 q4w 
o 32 mg (0.64 mL) CAM2038 q1w:  128 mg (0.36 mL) CAM2038 q4w 
In addition, per Investigator’s discretion, subjects may be switched back from monthly 
CAM2038 q4w visits to CAM2038 q1w weekly visits at any time during the Treatment Phase, if 
weekly dose visits are deemed to be appropriate based on the Investigator’s clinical judgment on 
subject’s level of stability.  
Subjects receiving CAM2038 q4w will return to the clinic monthly to receive their next dose, 
and for safety and other assessments outlined in Table 3. 
Subjects may receive temporary dose adjustment while receiving CAM2038 q4w, at the 
Investigator’s discretion, using booster CAM2038 q1w 8 mg SC injections at any time during the 
study (through unscheduled visits, as needed). At the discretion of the Investigator, subjects may 
also receive dose adjustments during the scheduled CAM2038 q4w monthly dose visits. The 
temporary dose adjustments, or booster CAM2038 q1w 8 mg SC injection may be given at a 
maximum of two boosters per week. 
At each visit (weekly or monthly), the following will be assessed: 
• Urine samples for opioid toxicology, evaluated using immunoassay (qualitative) with 
reflex quantitative confirmation methods. Urine will also be tested for other drugs of 
abuse (e. g., cocaine, benzodiazepines, barbiturates, amphetamines, phencyclidine, and 
THC) and for alcohol using qualitative methods. 
• Self-reported use of all drugs, including illicit or prescription opioids and other 
prescribed or illicit drugs. 
• Measures of withdrawal using the Clinical Opioid Withdrawal Scale (COWS) and the 
Subjective Opioid Withdrawal Scale (SOWS) 
• Measures of craving using Desire to Use and Need to Use visual analog scales (VAS) 
• Other safety assessments and measures as outlined in Table 3.  
7.1.3. 
Follow-up Phase (Week 49 to 53): 
Following the last Treatment Visit, subjects will be transitioned to standard care (e.g., SL 
BPN/BPX) at Week 49. Additional assessments will be performed during Week 53 outlined in 
Table 3. 


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7.2. 
Discussion of Study Design 
The evaluation of safety will be performed in an open-label manner, consistent with standard 
practice for long-term safety follow-up studies. The use of a placebo-controlled study was 
considered unethical due to the high risk of failure of these patients on placebo treatment, and the 
potential harms associated with treatment failure (FDA CDER and CBER, 2010).  A broad group 
of potential subjects will be eligible for participation as well as subjects not currently receiving 
BPN treatment.  
7.3. 
Selection of Study Population 
The study will enroll approximately 228 subjects (new entrants to CAM2038 treatment) with an 
approximate dropout rate of approximately 50% to ensure at least 100 subjects have exposure to 
CAM2038 for up to 48 weeks. The study will end after at least 100 subjects have been exposed 
to CAM2038 for 48 weeks. 
This study will enroll adult outpatients with opioid use disorder, as defined by the Diagnostic and 
Statistical Manual of Mental Disorders – Fifth Edition (DSM-V).   
7.4. 
Inclusion Criteria 
Subjects must meet each one of the following inclusion criteria in order to be eligible for 
participation in the study: 
1. Subject must provide written informed consent prior to the conduct of any study-related 
procedures.  
2. Male or female, 18-65 years of age, inclusive.  
3. Female subjects of childbearing potential must be willing to use a highly effective 
method of contraception during the entire study (Screening Visit to Follow-Up Visit) 
(Section 9.1.6).  
4. Current diagnosis of moderate or severe opioid use disorder (DSM-V) or past medical 
history of opioid use disorder currently being treated with SL BPN.  
5. Considered by the Investigator to be a good candidate for BPN treatment, based on 
medical and psychosocial history. 
6. Subjects must meet one of the following criteria for BPN treatment history: 
a. Voluntarily seeking treatment for opioid use disorder (not currently on BPN 
treatment for at least last 60 days but seeking BPN treatment), or; 
b. Currently on SL BPN treatment.  
7.5. 
Exclusion Criteria 
Subjects will not be eligible to participate in this study if any one of the following exclusion 
criteria is met: 


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1. Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS).  
2. Current diagnosis of chronic pain requiring opioids for treatment. 
3. Current DSM-V diagnosis for moderate to severe substance use disorder (including 
alcohol) other than opioids, caffeine or nicotine and currently being treated as the 
primary substance use disorder. 
4. Recent history of or current evidence of suicidal ideation or active suicidal behavior as 
based on the Columbia Suicide Severity Rating Scale (C-SSRS) (“Yes” responses to 
questions 4 or 5). 
5. Pregnant or lactating or planning to become pregnant during the study.   
6. Hypersensitivity or allergy to naloxone (only for subjects receiving the SL BPX test 
dose), BPN or excipients of CAM2038.  
7. Requires chronic use of agents that are strong inhibitors or inducers of cytochrome 
P450 3A4 (CYP 3A4) such as some azole antifungals (e.g., ketoconazole), macrolide 
antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and 
saquinavir).  
8. Hepatitis, unless under stable treatment, at the discretion of the Investigator. 
9. Any pending legal action that could prohibit participation or compliance in the study. 
10. Exposure to any investigational drug within the 4 weeks prior to Screening. 
11. Aspartate aminotransferase (AST) levels ≥3 X the upper limit of normal, alanine 
aminotransferase (ALT), levels ≥ 3 X the upper limit of normal, total bilirubin ≥ 1.5 X 
the upper limit of normal, or creatinine ≥ 1.5 X upper limit of normal on the Screening 
laboratory assessments, or other clinically significant laboratory abnormalities, which 
in the opinion of the Investigator may prevent the subject from safely participating in 
study.  
12. Participants with a history of risk factors of Torsades de Pointes (e.g., heart failure, 
hypokalemia, family history of Long QT Syndrome) or an ECG demonstrating a 
Fridericia's corrected QT interval (QTcF) >450 msec in males and QTcF > 470 in 
females at screening. 
13. Significant symptoms, medical conditions, or other circumstances which, in the opinion 
of the Investigator, would preclude compliance with the protocol, adequate cooperation 
in the study or obtaining informed consent, or may prevent the subject from safely 
participating in study. This includes, but is not limited to, subjects with attention deficit 
hyperactivity disorder receiving central stimulants (e.g. methylphenidate or other 
central stimulants), as well as subjects with severe respiratory insufficiency, respiratory 
depression, airway obstruction, gastrointestinal motility disorders, severe hepatic 
insufficiency, planned surgery and prior treatment with monoamine oxidase inhibitors. 
14. Is an employee of the Investigator or the trial site, with direct involvement in the 
proposed trial or other studies under the direction of the Investigator or trial site, or is a 
family member of an employee or of the Investigator. 


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7.6. 
Removal of Subjects from Therapy or Assessment 
A subject is free to withdraw his/her consent and discontinue participation in the study at any 
time for any reason. A subject’s participation must therefore be terminated immediately upon 
his/her request, and the reason(s) for discontinuation appropriately documented. 
A subject must be discontinued from the study for any of the following reasons: 
§ Safety reasons, including AEs or significant concomitant illness, increased concomitant 
use of recreational drugs, alcohol, psychotropic agents or methadone, injury, or urgent 
surgeries/procedures that would, in the judgment of the Investigator, affect assessments of 
clinical status to a significant extent, require discontinuation of study drug, or both 
§ At the request of the Sponsor, regulatory agency, or Institutional Review Board (IRB) 
§ Subject is lost to follow-up 
§ Pregnancy (UK only) 
§ Death of subject 
A subject may also be discontinued from the study, at the discretion of the Investigator and/or 
Sponsor, for any of the following reasons:  
§ Subject refuses or is unable to adhere to the study protocol 
§ Protocol violation 
§ Pregnancy (in the UK, pregnant subjects must be discontinued, see above) 
§ Requirement for continual use of opioid analgesics >7 days or requirement for general 
anesthesia for surgery 
The Investigator must maintain a record of all subjects who discontinue from the study prior to 
completion; the reason(s) for study discontinuation will be documented. In the event that a 
subject chooses to withdraw from the study, the Investigator should make a reasonable attempt to 
obtain and record the reason(s) for withdrawal, if possible, although the subject is not obligated 
to provide such a reason.  
All efforts should be made by the Investigator to continue collection of safety assessments at the 
protocol-defined study visit intervals, including concomitant medications, and AEs in subjects 
that discontinue study drugs, unless the subject withdraws his/her consent at the time of early 
discontinuation. The Investigator should also ask the subject to return for the Follow-up 
assessments, provided that the subject has not withdrawn consent for those assessments. If a 
subject refuses to complete early termination procedures and/or Follow-up, this information will 
be recorded. 


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8. 
TREATMENTS 
8.1. 
Treatment Administration 
Subjects will receive CAM2038 treatment for up to 12 months (48 weeks) during the study:  
§ For subjects who are not currently receiving SL BPN or SL BPN/BPX, treatment will be 
initiated with a single CAM2038 q1w 16 mg SC injection (following a 4 mg SL BPX test 
dose); additional dose adjustments will be allowed up to maximum weekly dose of 
40 mg.  
§ Subjects who are currently receiving SL BPN/BPX will be transitioned to CAM2038 q1w 
or q4w SC injections according to their current dose of SL BPN/BPX (Table 2).  
§ SC injection administration sites:  Rotate from left and right side of buttock. Injection 
with CAM2038 q1w will be rotated in a manner to not re-inject in the same location for 
at least 8 weeks, (i.e., injection into the same site will only occur after 8 weeks). Injection 
with CAM2038 q4w will be rotated and the same site will not be utilized for the duration 
of the study.  
§ Additionally, a q4w injection dose can be injected into a previously used q1w injection 
site following the q1w rule: Injection with CAM2038 q1w will be rotated in a manner to 
not re-inject in the same location for at least 8 weeks, (i.e., injection into the same site 
will only occur after 8 weeks  
 
A diagram of potential injection sites will be provided in the Study Manual of Procedures 
(MOP). 
  
Table 2: Doses of CAM2038 q1w and q4w for Subjects Transitioning from SL BPN/BPX 
Weekly SL BPN/BPX Category 
Once Weekly CAM2038 q1w SC Injectiona 
≤ 6 mg 
8 mg (0.16 mL)  
8-10 mg  
16 mg (0.32 mL)  
12-16 mg  
24 mg (0.48 mL)  
18-24 mg  
32 mg (0.64 mL)  
Monthly SL BPN Category 
Once Monthly CAM2038 q4w SC Injectionb 
8-10 mg  
64 mg (0.18 mL)  
12-16 mg  
96 mg (0.27 mL)  
18-24 mg  
128 mg (0.36 mL)  


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26-32 mg  
160 mg (0.45 mL)  
BPN = buprenorphine; BPX = buprenorphine/naloxone; SC = subcutaneous; SL = sublingual 
a Subjects may return to the clinic for additional dose adjustments with CAM2038 q1w at scheduled visits or 8 mg 
SC booster injections at unscheduled visits, as needed, up to a maximum weekly dose of 40 mg per week. 
b Subjects needing additional temporary BPN while receiving CAM2038 q4w may receive a maximum of two 
boosters of CAM2038 q1w 8 mg SC injection per week (i.e., unscheduled visits). Dose adjustments may also be 
implemented at the discretion of the Investigator at scheduled visits.  
8.2. 
Identity of Investigational Product(s) 
The following treatments will be used during the study:  
§ CAM2038 q1w (buprenorphine FluidCrystal® Injection depot for once weekly 
administration), 50 mg/mL: 8, 16, 24 and 32 mg (buprenorphine base), 0.16, 0.32, 0.48 
and 0.64 mL SC injection. 
§ CAM2038 q4w (buprenorphine FluidCrystal® Injection depot for once monthly 
administration), 356 mg/mL: 64, 96, 128 and 160 mg (buprenorphine base), 0.18, 0.27, 
0.36 and 0.45 mL SC injection.  
CAM2038 q1w will be supplied as pre-filled syringe with safety device and plunger containing 
the following: buprenorphine, soybean phosphatidylcholine, glycerol dioleate, and ethanol. 
CAM2038 q4w will be supplied as pre-filled syringe with safety device and plunger containing 
the following: buprenorphine, soybean phosphatidylcholine, glycerol dioleate, and N-Methyl-2-
pyrrolidone. 
More information regarding the CAM2038 q1w and q4w can be found in the Study MOP.   
All containers/packages /boxes of study drug will be clearly labeled with study-specific 
information meeting all the applicable regulatory/institutional requirements. 
8.2.1. 
Handling, Storage, and Accountability 
All study drugs will be transported, received, stored, and handled strictly in accordance with the 
container or product label, the instructions provided to the research site, and applicable 
regulations.  
CAM2038 products must be stored according to the requirements outlined in the Study MOP. 
Detailed drug accountability records must be maintained, including the dates shipments are 
received, the quantity of material received, the dates dispensed, the running inventory, and the 
unused quantities returned to the Sponsor’s drug supply vendor at the end of the trial. All unused 
supplies and empty IP kits from used injection depots will be checked against the drug 
accountability records during the study and/or at the end of the study. Additional details are 
provided in the Study MOP. 
Buprenorphine is a Schedule III controlled substance and study drugs must be handled and stored 
strictly in accordance with restrictions related to controlled substances. Study drugs must be kept 


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securely locked with access limited to appropriate study personnel, according to applicable 
regulations. 
8.2.2. 
Dispensing and Administration 
Only eligible subjects participating in the study will receive the study drug. Only authorized 
research site staff may supply or administer the study drugs. Once dispensed, study drug may not 
be relabeled or reassigned for use by other subjects.  
CAM2038 q1w and q4w SC injections will be administered by designated healthcare 
professional(s) at the investigational site. Detailed instructions for use will be provided in the 
Study MOP. 
Investigator will be instructed to treat additional symptoms as they would usually, including 
additional counseling sessions, CAM2038 q1w booster injections, or other pharmacological 
interventions. Any CAM2038 q1w booster injections, additional counseling, and other 
pharmacological interventions provided by the Investigator will be recorded, along with the 
reasons for determining the need for these interventions.   
8.2.3. 
Sublingual Buprenorphine/Naloxone 
Subjects who are not currently receiving SL BPN or SL BPN/BPX at the time of study entry will 
receive a 4 mg test dose of BPX on Day 1. The BPX test dose consists of 2 SL tablets of 
Suboxone®, each containing 2 mg BPN and 0.5 mg naloxone (Indivior UK Limited). Suboxone 
will be sourced locally, handling and storage of the product will be in accordance with the 
Suboxone Summary of Product Characteristics.  
8.3. 
Method of Assigning Subjects to Treatment Groups 
Subjects who have provided written informed consent will be assigned a unique number in the 
screening process. This number will be used to identify the subject throughout the study. 
Subjects will not be randomized to a treatment group; subjects who have met the eligibility 
criteria (Section 7.4) will receive CAM2038 q1w or CAM2038 q4w treatment based on their 
prior history of BPN treatment (Section 7.1.2 and 8.1). 
8.4. 
Selection of Doses 
The study will include the proposed range of CAM2038 q1w and q4w doses to be used in 
clinical practice, based on each subject’s individual needs. As in clinical practice, dose 
adjustments (increases in case of withdrawal effects or cravings or decreases for tolerability 
reasons) will be allowed during the study. In addition, booster injections of CAM2038 q1w 8 mg 
will be allowed during the study for those receiving either CAM2038 q1w or CAM2038 q4w (up 
to a maximum weekly dose of 40 mg per week for subjects receiving CAM2038 q1w, or a 
maximum of two boosters per week for subjects receiving CAM2038 q4w).  


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8.5. 
Selection and Timing of Dose 
Subjects will receive either CAM2038 q1w or CAM2038 q4w at individualized doses. The dose 
levels will be sufficient to prevent withdrawal symptoms and cravings, as in clinical practice. 
The SC injections may be given at any time during the day.   
No fasting or special dietary requirements are required for the study.  
8.6. 
Blinding 
This is an open-label study and no blinding will be used.  
8.7. 
Prior and Concomitant Therapy 
All non-study medications, including prescription, over-the-counter, or herbal therapies, used by 
the subject will be documented for the 30 days prior to Screening and throughout the study. The 
Investigator will determine if the prior/concomitant medication(s) affect the subject’s eligibility 
to participate or continue to participate in the study. The following restrictions on concomitant 
medications will be in place during the study:  
§ Opioid receptors are likely to be occupied by BPN, which may reduce the analgesic 
effects of an opioid. The dissociation of BPN from the receptors may take several days 
following discontinuation of SL BPN treatment or up to 2 weeks (q1w) or month 
following the last CAM2038 (q4w) injection. Therefore, subjects requiring analgesic 
emergency treatment or anesthesia for surgery should ideally be treated with a non-opioid 
analgesic. Opioids may be used with caution, but as higher doses may be required for 
analgesic effect, there may be a higher potential for toxicity with opioid administration. 
The clinical course should be carefully evaluated and fully documented for subjects who 
have a requirement for any opioid analgesic for >7 days continually or general anesthesia 
for surgery. 
§ Buprenorphine is metabolized via CYP3A4. Because CYP3A4 inhibitors may increase 
plasma concentrations of BPN, if CYP3A4 inhibitors such as azole antifungals (e.g., 
ketoconazole), macrolide antibiotics (e.g., erythromycin), and HIV protease inhibitors 
(e.g., ritonavir, indinavir, and saquinavir) are required, the Medical Monitor must be 
consulted. Interactions with CYP3A4 inducers have not been investigated; therefore it is 
recommended that the use of agents such as phenobarbital, carbamazepine, phenytoin and 
rifampicin be avoided in subjects receiving study treatment. The Medical Monitor must 
be consulted prior to starting subjects on any of these agents. 
§ Concomitant use of other narcotic anesthetics, analgesics, benzodiazepines, 
phenothiazines, other tranquilizers, or other central nervous system (CNS) depressants 
(including alcohol and sedative/hypnotics) may cause respiratory and CNS depression. 
Use of these substances should be minimized during treatment with CAM2038 or SL 
BPX. If patients are taking these sedatives during Screening, the Medical Monitor must 
be consulted to evaluate eligibility into the study, taking into consideration the stability of 
the patient on the sedatives.  If these sedatives are required during the study, the Medical 
Monitor must be consulted. Subjects must be advised of the danger of concomitant use of 


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sedatives while participating in in the study. Subjects should be explicitly advised of the 
danger of IV abuse of benzodiazepines and alcohol while under treatment with 
CAM2038. 


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9. 
STUDY PROCEDURES AND ASSESSMENTS 
All study assessments will be performed at the visits and time points outlined in the Schedule of 
Assessments (Table 3); the following sections outline the details and procedures associated with 
the assessments. Additional details on the assessments, including copies of questionnaires, logs, 
manuals, and information sheets are provided in the Study MOP.


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Table 3: Schedule of Assessments 
Study Phase: Screening 
Treatment Phase 
EOT 
Follow-
up 
Treatment: 
- 
CAM2038 
q1w or q4w 
CAM2038 q1w 
CAM2038 q4w 
 
All 
Subjects 
Study Population: 
All 
Subjectsa All Subjects 
New to BPN 
Treatmentb 
Transition from 
SL BPN/BPXc 
Transition 
from CAM2038 
q1wd 
Transition from SL BPN/BPX 
(Monthly)e 
 
Monthf: 
M-1 
M1 
M1 
M1 to Mx 
M1 to Mx 
Mx to M12g 
M1 to M12h 
 
M13 
Weekh: 
-3 
W1 
W1 
W2 to Wxi 
W1 to Wxi 
Wx to W48 
W1 to W48 
W49 
W53 
Day: 
- 
Day 1 
Day 2-7j 
- 
- 
- 
- 
 
- 
Informed Consentk 
X 
 
 
 
 
 
 
 
 
Eligibility Criteria Reviewl 
X 
X 
 
 
 
 
 
 
 
Medical and Medication Hx 
X 
 
 
 
 
 
 
 
 
Substance Abuse/Treatment Hx 
(questionnaires) 
X 
 
 
 
 
 
 
 
 
DSM-V  
X 
 
 
 
 
 
 
 
 
Physical Examinationm 
X 
 
 
 
 
 
 
 
 
 
a All subjects will undergo screening procedures. 
b Subjects seeking treatment with BPN, but treatment with BPN has not yet begun. 
c Subjects receiving SL BPN/BPX at the time of study entry and considered by the Investigator to be a candidate for CAM2038 q1w once weekly treatment. 
d Subjects who started treatment with CAM2038 q1w and are transitioned to CAM2038 q4w after meeting criteria. 
e Subjects receiving SL BPN/BPX at the time of study entry and considered by the Investigator to be a candidate for CAM2038 q4w once monthly treatment.  
f A window of ±7 days will be allowed for monthly visits. 
g The last monthly injection will be administered at the end of Month 11 (Week 45); additional assessments will be performed at the Week 49 visit, including 
transition back to usual care. 
h A window of ±3 days will be allowed for weekly visits. 
i  Subjects may transition to CAM2038 q4w and monthly visits at any time during the 12 months, once they meet criteria for transitioning (Section 7.1.2). 
j A window of ±1 day will be allowed for the visit performed on Day 4. 
k Subjects must voluntarily provide written informed consent prior to any study-related procedures being performed. 
l Prior to enrollment in the Treatment Phase of this study, all Inclusion and Exclusion criteria must be met.  
m A complete physical exam of all major body systems will be performed at the Screening Visit. 


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Study Phase: Screening 
Treatment Phase 
EOT 
Follow-
up 
Treatment: 
- 
CAM2038 
q1w or q4w 
CAM2038 q1w 
CAM2038 q4w 
 
All 
Subjects 
Study Population: 
All 
Subjectsa All Subjects 
New to BPN 
Treatmentb 
Transition from 
SL BPN/BPXc 
Transition 
from CAM2038 
q1wd 
Transition from SL BPN/BPX 
(Monthly)e 
 
Monthf: 
M-1 
M1 
M1 
M1 to Mx 
M1 to Mx 
Mx to M12g 
M1 to M12h 
 
M13 
Weekh: 
-3 
W1 
W1 
W2 to Wxi 
W1 to Wxi 
Wx to W48 
W1 to W48 
W49 
W53 
Day: 
- 
Day 1 
Day 2-7j 
- 
- 
- 
- 
 
- 
Weight, BMI 
X 
X 
 
Monthly 
Monthly 
Monthly 
Monthly 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Abbreviated Review of Systems 
 
X 
 
 
 
 
 
X 
 
Vital Signsn 
X 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
X 
ECG 
X 
 
 
Xo 
Xo 
Xo 
Xo 
X 
 
Laboratory testsp 
X 
 
 
 
 
 
 
X 
 
Pregnancy Testq 
X 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
 
Hepatitis B/C, HIVr 
X 
 
 
 
 
 
 
 
 
Injection Site Examination 
 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
X 
Dispense Treatment ID Card 
 
X 
 
 
 
 
 
 
 
Urine Toxicology 
X 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
 
Illicit Drug Use Self-Report  
X 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
 
SOWS, COWS VAS 
X 
X 
(X) 
Monthly 
Monthly 
Monthly 
Monthly 
X 
 
EQ-5D-5L 
X 
X 
 
Monthly 
Monthly 
Monthly 
Monthly 
X 
 
 
n Includes temperature, blood pressure, pulse rate, respiration rate. 
o ECG will be performed after the first administration of CAM2038 q1w or CAM2038 q4w (i.e., prior to dosing at Week 2 for CAM2038 q1w or Week 5 for 
CAM2038 q4w). During the study, ECGs will be performed after dose increases (excluding the initial dose titration and booster injections) and after intake of 
QT-extending drugs or CYP3A4 inhibitors. 
p Includes chemistry, hematology, urinalysis and coagulation profile.  
q A serum pregnancy test will be performed at Screening and EOT (Week 49). An “in-office” urine pregnancy test will be required at Day 1 PRIOR to the first 
injection of CAM2038 and then at each visit thereafter (for women of childbearing potential).   
r It is the Investigator’s responsibility to understand and comply with all laws and regulations that apply to HIV, Hepatitis B, and Hepatitis C and testing of blood.  
Hepatitis B/C and HIV testing is required unless a site’s IRB prohibits such testing. 


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Study Phase: Screening 
Treatment Phase 
EOT 
Follow-
up 
Treatment: 
- 
CAM2038 
q1w or q4w 
CAM2038 q1w 
CAM2038 q4w 
 
All 
Subjects 
Study Population: 
All 
Subjectsa All Subjects 
New to BPN 
Treatmentb 
Transition from 
SL BPN/BPXc 
Transition 
from CAM2038 
q1wd 
Transition from SL BPN/BPX 
(Monthly)e 
 
Monthf: 
M-1 
M1 
M1 
M1 to Mx 
M1 to Mx 
Mx to M12g 
M1 to M12h 
 
M13 
Weekh: 
-3 
W1 
W1 
W2 to Wxi 
W1 to Wxi 
Wx to W48 
W1 to W48 
W49 
W53 
Day: 
- 
Day 1 
Day 2-7j 
- 
- 
- 
- 
 
- 
WPAI-GH 
X 
X 
 
Monthly 
Monthly 
Monthly 
Monthly 
X 
 
Patient Satisfaction  
 
 
 
Month 6 
Month 6 
Month 6 
Month 6 
X 
 
C-SSRSs 
X 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
X 
CAM2038 SC injectiont 
 
X 
(X) 
Weekly 
Weekly 
Monthly 
Monthly 
 
 
Psychosocial Counseling 
 
X 
 
Monthly 
Monthly 
Monthly 
Monthly 
 
 
Adverse Eventsu 
X 
X 
(X) 
Weekly 
Weekly 
Monthly 
Monthly 
X 
X 
Concomitant Meds/Procedures 
X 
X 
 
Weekly 
Weekly 
Monthly 
Monthly 
X 
X 
On-site Visits 
X 
X 
(X) 
Weekly 
Weekly 
Monthly 
Monthly  
X 
X 
Abbreviations: BMI=Body Mass Index; COWS=Clinical Opiate Withdrawal Scale; C-SSRS=Columbia Suicide Severity Rating Scale; DSM-V=Diagnostic and 
Statistical Manual of Mental Disorders – Fifth Edition; ECG=electrocardiogram; HIV=Human Immunodeficiency Virus; Hx=history; ID= identification; M= 
month; SC=subcutaneous; SOWS=Subjective Opioid Withdrawal Scale; VAS=visual analogue scale; W= week; WPAI-GH=Work Productivity and Activity 
Impairment Questionnaire-General Health; (X)=optional visit based on individual subject titration needs.
 
s Screening version at Visit 1 (Screening), Since Last Visit version at all subsequent visits. 
t CAM2038 q1w for weekly visits and CAM2038 q4w for monthly visits. 
u Any spontaneously reported adverse events will be recorded after the subject signs the informed consent form. In addition, adverse events will be elicited using 
a non-leading question each time the subject visits the clinic. 


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9.1. 
Demographics and Other Baseline Characteristics 
9.1.1. 
Informed Consent 
The nature of the study and its risks and benefits will be explained to the subject by the 
Investigator or designated study personnel. The subject must voluntarily provide written 
informed consent on an ethics-approved informed consent form (ICF), prior to performing any 
study-related procedures. The subject’s medical records must document that the consent process 
has been completed and that written informed consent has been obtained from the subject prior 
to the initiation of any study-specific procedures. Documentation that the subject was given 
adequate time to ask the Investigator (or designee) questions about their participation in the study 
and that a signed and dated copy of the ICF was provided to the subject should also be included 
in the medical records or clinical chart. 
9.1.2. 
Demographics 
The following demographics will be recorded: age (birthdate), sex, race, and ethnicity. A 
complete psychosocial history will be obtained including education, employment status, 
marital/significant other status, residential status and legal status/arrest history.   
9.1.3. 
Medical History 
The complete medical history based on patient interview of 5 years prior to the screening visit 
and any clinically significant medical history greater than 5 years prior to the screening visit will 
be collected, these will include histories of acute, chronic, or infectious disease; surgical or 
oncologic histories; and any reported conditions affecting major body systems. All findings on 
medical history will be evaluated by the Investigator for clinical significance. 
9.1.4. 
Medication History  
All medications (prescription and non-prescription, herbal medications/natural health products, 
or investigational drugs) taken by the subjects during the 30 days prior to Screening will be 
recorded in the source documentation as medication history. Substance Abuse History and 
Treatments will be collected separately. 
9.1.5. 
Substance Use and Treatment History 
A complete history of previous and current illicit drug use, substance abuse/dependence, and 
treatments for any substance use disorders (pharmacologic as well as non-pharmacologic) will be 
obtained. This will include drugs used, type, frequency and patterns of abuse, routes, doses, drug 
preferences and concomitant medications, using questionnaires. Detailed information on 
substance use and treatment history is provided in the Study MOP.  
9.1.6. 
Contraceptive Requirements 
Women of childbearing potential must agree to use highly-effective method(s) of birth control as 
defined in the informed consent form and must agree to be tested for pregnancy. 
 
Highly-effective method(s) of birth control include: 


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• Established use of progestogen-only oral, injectable or implantable hormonal methods of 
contraception (for example contraceptive pills, implants, transdermal patches, hormonal 
vaginal devices or injections with prolonged release). 
• Established use of combined estrogen and progestogen oral, intravaginal or transdermal 
hormonal methods of contraception (for example contraceptive pills, implants, 
transdermal patches, hormonal vaginal devices or injections with prolonged release). 
• Placement of an intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS). 
• Vasectomized male partner (with the appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate and provided this partner is the sole sexual partner of 
the female study participant of childbearing potential). 
 
Male subjects must agree to use condoms throughout the course of the study (from Screening to 
Follow-up). 
 
Women of childbearing potential must have a confirmed negative pregnancy test at study entry. 
They must use an effective contraceptive method throughout the entire duration of the study 
treatment, and agree to repeat urine pregnancy test at designated visits. The applied methods of 
contraception have to meet the above criteria for a highly effective method of birth control.  
 
Sterilized or infertile subjects are exempt from the requirement to use contraception. In order to 
be considered sterilized or infertile, subjects must have undergone surgical sterilization 
(vasectomy/bilateral tubectomy, hysterectomy and bilateral ovariectomy, as determined by 
subject medical history) or congenially sterile, or must be post-menopausal. Postmenopausal 
women must be amenorrheic for at least 12 months. 
9.2. 
Eligibility Review  
Prior to receiving CAM2038 on Day 1, subjects must meet all inclusion and not meet any 
exclusion criteria as outlined in Section 7.4 and 7.5. 
The Investigator or Sub-Investigator must document that the subjects meet each individual 
criterion via a signed note or eligibility and clinical stability checklist during Screening. 
Signatures on these documents must be dated on or before the date of Day 1.  
9.3. 
Efficacy Assessments 
Details regarding exploratory efficacy endpoints are provided in Section 9.6 (Efficacy Variables). 
The following sections provide an overview of the efficacy assessments included in the study.  
Additional details, such as the questionnaire items/scale text and additional instructions (where 
applicable) are provided in the Study MOP.  
9.3.1. 
Urine Toxicology for Opioids 
Urine toxicology samples will be collected at each visit using a urine collection cup containing a 
temperature sensor. Specimen authenticity will be verified at the site using this sensor to measure 


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the urine temperature immediately following collection. The temperature of a urine sample 
within 4 minutes of voiding should fall within the range of 32.2 to 37.7 degrees Celsius (90 to 
100 degrees Fahrenheit). If test results are outside these ranges, the subject will be asked to 
immediately provide another urine sample. If this second sample is outside of the temperature 
range, the sample will be counted as 'missing', and should not be sent for analysis (any such 
samples must be documented in the subject’s records). A direct observation approach to 
obtaining urine samples may be used if the Investigator deems it necessary (in Sweden and 
France, supervision of urine sampling is mandatory). Urine samples will be logged and 
numbered and then sent to a central laboratory for analysis for the presence of opioids (e.g., 
morphine and metabolites, oxycodone, hydrocodone, hydromorphone, fentanyl, and methadone). 
In addition, it is recommended that the scheduled assessment visits take place on Mondays to 
potentially improve detection of illicit opioid use that may have occurred over the weekend. 
9.3.2. 
Self-Reported Illicit Drug Use  
Subjects will be questioned about illicit drug use, including illicit or prescription opioids and 
other drugs of abuse using a timeline follow-back type of interview (Fals-Stewart et al, 2000).  A 
copy of the Illicit Drug Use Self-Report form is provided in the Study MOP.  
 
9.3.3. 
Measures of Desire and Need to Use 
Desire to Use and Need to Use will be administered using unipolar 100 mm VAS (“Since your 
last scheduled assessment visit, indicate your worst or strongest desire/need to use opioids, 
where 0 = No desire to use and 100 mm= Strongest possible desire, and from 0=No need to use 
and 100 mm=Strongest possible need, respectively) outcome (Kozlowski et al, 1989).  
Copies of these VASs are provided in the Study MOP. NOTE: Only VAS copies provided by the 
Sponsor should be used with study subjects; photocopies made locally may result in changes to 
the length of the scale, leading to inaccurate results.  
A separate VAS will be provided for each Desire to Use and Need to Use and measurements 
must be taken separately (i.e., separated in time or by other procedures). 
9.3.4. 
Quality of Life Questionnaires and Patient Satisfaction Scale 
Two quality of life questionnaires will be provided to subjects for completion: 
• Work Productivity and Activity Impairment Questionnaire-General Health (WPAI-GH) 
(Reilly Associates). 
• EQ-5D-5L Health Questionnaire (EuroQOL Group Association). 
These are to be completed on a monthly basis, approximately every four weeks at the subjects 
scheduled visit. 
 
A patient satisfaction scale will be provided to subjects for completion at month 6 and month 12 
(EOT). 
 
Copies of the WPAI-GH, EQ-5D-5L and patient satisfaction scale is provided in the Study MOP. 
 


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9.3.5. 
Measures of Withdrawal  
9.3.5.1. 
Subjective Opioid Withdrawal Scale (SOWS)  
Subjects will complete a self-assessment of withdrawal symptoms using the SOWS. This form 
contains 16 questions that rate the intensity of withdrawal from 0 (“Not at all”) to 4 
(“Extremely”).  A copy of the SOWS is provided in the Study MOP. 
9.3.5.2. 
Clinical Opioid Withdrawal Scale (COWS) 
Study personnel will assess clinical observations indicative of withdrawal using the COWS. This 
scale consists of 11 common opiate withdrawal signs or symptoms, rated on a numeric scale and 
based on a timed period of observation of the subject by the rater.  A copy of the COWS is 
provided in the Study MOP. 
9.3.6. 
Urine Toxicology for Other Drugs of Abuse 
Urine will be tested for other drugs of abuse (e.g., cocaine, benzodiazepines, barbiturates, 
amphetamines, phencyclidine and cannabinoids [THC]) and for alcohol using qualitative 
methods. Positive results will not be confirmed using quantitative methods.  
9.3.7. 
Unscheduled Visits, Medication and Counseling 
Temporary adjustments in BPN doses will be allowed using CAM2038 q1w SC booster 
injections (8 mg) at unscheduled visit(s). A maximum of two SC booster injections will be 
allowed per week. Subject-requested or physician-directed supplemental visits, phone calls or 
additional counseling, or other pharmacological interventions, along with the reason(s) for 
unscheduled visits, booster injections, phone calls or additional counseling or other 
pharmacological interventions, will be recorded. 
9.4. 
Safety Assessments 
Safety monitoring will be performed throughout the study for all subjects. All AEs, regardless of 
causality or severity, will be recorded on the AE CRF. CAM2038 injections may be discontinued 
as clinically indicated. 
9.4.1. 
Adverse Events and Serious Adverse Events 
The following definitions, developed in accordance with the United States (US) Code of Federal 
Regulations (CFR) and the International Conference on Harmonization (ICH) Clinical Safety 
Data Management Guidance for Industry, E2A, will be used for the purpose of identifying AEs 
in this clinical study. 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product 
that does not necessarily have a causal relationship with this treatment. An AE can therefore be 
any unfavorable and unintended sign (e.g., including an abnormal laboratory finding), symptom, 
or increase in severity of a preexisting abnormality, temporally associated with the use of a 
medicinal (investigational) product, whether or not considered related to the medicinal 
(investigational) product. 


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9.4.1.1. 
Adverse Event Reporting 
All AEs (except for withdrawal symptoms, see below) must be entered on the AE CRF, 
regardless of causality or severity. AEs include new AEs, worsening baseline conditions, 
clinically significant laboratory findings, disease-related signs and symptoms that were not 
present at baseline, and any events or findings that the Investigator feels are clinically significant. 
Withdrawal symptoms will be captured via specified assessments and should not be recorded as 
AEs. 
Disease-related signs and symptoms that are present at baseline should not be recorded as AEs 
unless they worsen in severity or increase in frequency. 
Information collected concerning AEs will include the following: 
§ Name of the event 
§ Onset date 
§ Resolution date 
§ Severity (i.e., mild, moderate, or severe) 
§ Relationship to study drug 
§ Action and outcome 
§ Seriousness of event 
Definition of MILD, MODERATE, SEVERE AE: 
§ Mild- An AE that requires minimal treatment and does not interfere with daily living. 
§ Moderate-An AE that requires therapeutic intervention and interferes with daily living. 
§ Severe-An AE that requires intensive therapeutic intervention, significant, etc. 
 
All AEs will be documented and followed from the time the subject has signed the ICF until 
14 days after the Follow-up Visit (or 30 days after early termination). Serious AEs and AEs that 
have been designated as possibly related to study drug will be followed until resolution or 
stabilization. 
9.4.1.2. 
Serious Adverse Event (SAE) 
An SAE or reaction is any adverse drug experience occurring at any dose that results in any of 
the following outcomes: 
§ Death 
§ Is life-threatening (at the time of the event) 
§ Requires inpatient hospitalization or prolongation of existing hospitalization, 
§ Results in persistent or significant disability/incapacity 
§ Is a congenital anomaly/birth defect (in an offspring) 


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§ An Important medical event that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, the event may jeopardize the subject and/or may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
All AEs requiring hospitalization or prolongation of a pre-existing hospitalization should be 
reported as SAEs unless they occur greater than 14 days after the Follow-up Visit (or 30 days 
after early termination) AND are not considered to be drug-related by the Investigator. 
Hospitalizations meeting the following criteria will not be reported as an SAE but must be 
recorded on the appropriate CRF: study specified hospitalization, short-term administrative 
hospitalization for procedures, tests or treatments of conditions that would not otherwise 
constitute an SAE, elective hospitalizations. 
9.4.1.2.1. Serious Adverse Event Reporting 
Serious AEs must be reported to the Sponsor or designee within 24 hours of knowledge of the 
event. All SAEs that occur while a subject is receiving study drug and within 14 days following 
the Follow-up Visit (or 30 days after early termination) are reportable within 24 hours. During 
the follow-up period beyond 14 days from Follow-up (or 30 days after early termination), only 
those SAEs that are considered to be possibly related to study drug should be reported within 
24 hours. 
The procedure for reporting an SAE is as follows: 
§ Within 24 hours of knowledge of the event, the site must contact the Sponsor (or 
designee) by telephone or facsimile to report the event. 
§ The initial report should include all information known at the time of the report 
(additional information can be reported as discovered). Do not delay the initial reporting 
in order to obtain resolution or follow-up information. 
§ The site will enter into the electronic database (or fax, if the database cannot be accessed 
for any reason) an SAE report, or similar form, that includes the following information, 
as available: 
o Subject ID 
o Basic demographic information (age, gender, weight) 
o Outcomes attributed to the event (death, life-threatening hospitalization [new or 
prolonged], disability, congenital anomaly, required medical intervention to 
prevent permanent impairment/damage, etc.) 
o Onset date and severity of the event 
o Brief description of the event including frequency and severity of symptoms 
leading to diagnosis 
o List of relevant test results and laboratory data 
o Any other relevant history 
o Whether the study drug was discontinued 


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o Whether the assigned treatment oral or injectable therapy was discontinued and/or 
dose titration discontinued, as applicable 
o Investigator’s assessment of causality 
The Medical Monitor or another representative of the Sponsor may contact the Investigator to 
request additional information regarding the event or to confirm information. All SAEs will be 
entered on the AE CRF. The same nomenclature should be used on both the SAE report and the 
AE CRF. 
Specific instructions for SAE reporting and a copy of an SAE report form are provided in the 
MOP. 
The Investigator is responsible for the complete and timely reporting of all SAEs to the Sponsor 
(or designee), reporting pertinent follow-up information on the SAE, and notifying the 
appropriate IRB/Independent Ethics Committee (IEC) of the occurrence of and details 
surrounding the event. In the event there is a question as to whether the AE is serious, the event 
should be reported. 
9.4.1.2.2. Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is defined as an SAE and where: 
§ 
There is a certain degree of probability that the event is harmful, and an undesirable, 
reaction to the medicinal product being research, regardless of the administered dosage. 
In other words, there is an adverse reaction. 
§ 
The adverse reaction is unexpected. That is to say, the nature and severity of the adverse 
reaction are not in agreement with the reference safety information as recorded in the 
Investigator’s Brochure. 
A SUSAR has additional reporting requirements, as described below. 
§ 
If the SUSAR is fatal or life-threatening, associated with the use of the investigational 
medicinal product, and unexpected, competent authorities and ethics committees will be 
notified within 7 calendar days after the Investigator learns of the event. Additional 
follow-up information (cause of death, autopsy report, hospital report) should be reported 
within an additional 8 days (15 days in total). 
§ 
If the SUSAR is not fatal or life-threatening but is otherwise serious, associated with the 
use of the investigational medicinal product, and unexpected, competent authorities and 
ethics committees will be notified within 15 calendar days after the Investigator learns of 
the event. 
All Investigators will receive relevant information about SUSARs in a timely fashion. Follow-up 
information may be submitted if necessary. 
9.4.2. 
Pregnancy 
Pregnancies among trial participants or their partners should be reported to the Sponsor or 
designee as soon as possible after learning of the event. Subjects who become pregnant may 
withdraw their consent and discontinue the study and be referred back to the care of their usual 
provider or continue in the study after discussion with and documentation by the Principal 


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Investigator or his/her designee. (In the UK, participants who become pregnant will be 
discontinued from the study permanently and be referred back to the care of their usual provider.) 
Follow-up information will be obtained where possible (with the consent of the participant or 
their partner) regarding the course and outcome of the pregnancy, including any post-natal 
sequelae in the infant during the first year of life. 
9.4.3. 
Clinical Laboratory Assessments 
All protocol-specified laboratory tests on blood and urine samples will be performed at a selected 
central laboratory, with the exception of urine pregnancy tests that are conducted at the study 
site. The central lab will generate laboratory reports and forward them to the clinical site in a 
timely manner. It is the responsibility of the Investigator to review and sign all lab reports 
expeditiously, in order to document appropriate safety monitoring of study subjects. The 
Investigator should sign and date each lab report concurrent with her or his review, and should 
indicate the clinical significance of each abnormal/flagged value by noting “NCS” (not clinically 
significant) or “CS” (clinically significant), for example. Notations indicating that a value is 
clinically significant should also include a brief description of the underlying disease or 
condition that is associated with the value, e.g., “CS/mild anemia.” Per investigator judgment, 
abnormal, clinically significant laboratory values are expected to be associated with an item 
recorded in medical history or with an AE. 
Blood and urine samples will be collected, processed, and shipped according to instructions from 
the safety laboratory. Additional laboratory samples may be taken at the discretion of the 
Investigator if the results of any tests fall outside reference ranges or clinical symptoms 
necessitate testing to ensure safety. Specific hematology, coagulation, biochemistry, and 
urinalysis assessments are listed in Table 4. 


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Table 4: Clinical Laboratory Assessments  
Hematology 
Biochemistry 
Urinalysis 
Hematocrit 
Hemoglobin 
Red blood cell (RBC) count  
RBC Morphology 
Mean corpuscular volume  
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin 
concentration  
Total and differential (absolute) 
white blood cell count 
Platelets 
Sodium 
Potassium 
Magnesium  
Calcium  
Glucose (random) 
Bicarbonate  
Chloride  
Creatinine 
Total protein 
Blood urea nitrogen  
Albumin 
Total bilirubin 
Alanine transferase  
Aspartate transferase  
Lactic dehydrogenase  
Amylase  
Lipase 
Gamma-glutamyl transferase  
Alkaline phosphatase  
Creatine phosphokinase  
Total cholesterol (non-fasting) 
Color 
pH 
Specific gravity 
Ketones 
Protein 
Glucose 
Bilirubin 
Nitrite 
Urobilinogen 
Occult blood 
Microscopic examination of 
sediment, only if urinalysis 
dipstick results are abnormal 
 
 
Coagulation 
Prothrombin time (PT), 
International normalized ratio 
(INR) 
 
In addition to the clinical laboratory tests, a serum pregnancy test will be performed at the 
Screening Visit and the End of Treatment Visit. An “in-office” urine pregnancy test will be 
required at Day 1 PRIOR to first CAM2038 administration, and then at each visit prior to 
administration of CAM2038 (for women of childbearing potential). Results must be reviewed 
and confirmed to be negative prior to start of CAM2038 treatment (Day 1). 
A blood sample for a serology panel testing for hepatitis B surface antigen, anti-hepatitis C 
antibodies, and HIV will be performed for all subjects, unless a site’s IRB prohibits such testing. 
It is the Investigator’s responsibility to understand and comply with all laws and regulations that 
apply to the testing of blood for HIV and hepatitis B and C. These laws and regulations may 
include state laws related to written consent, separate from the ICF for this study, and pre- and 
post-test counseling. 


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9.4.4. 
Vital Signs 
Vital signs will consist of temperature, blood pressure (systolic and diastolic blood pressure, 
mmHg), pulse rate (beats per minute), and respiratory rate (breaths/min) collected while sitting, 
following a rest period of at least 3 minutes.  
9.4.5. 
12-Lead Electrocardiogram (ECG) 
12-Lead ECGs will be performed after the subject has been resting in a recumbent/supine 
position for at least 3 minutes. The ECG variables will include ventricular heart rate and the PR, 
QRS, QT, QTcB and QTcF intervals. The ECGs will be signed and dated by a medically-
qualified individual to confirm review of the ECG and verify whether any abnormalities are 
clinically significant. In general, abnormal, clinically significant ECGs are expected to be 
associated with an item recorded in medical history or with an AE. 
ECGs will be performed at Screening and at the EOT visit. In addition, ECGs will be performed 
after the first administration of CAM2038 q1w or CAM2038 q4w (i.e., prior to dosing at Week 2 
for CAM2038 q1w or Week 5 for CAM2038 q4w). ECGs will also be performed in connection 
to dose increases (excluding the initial dose titration and booster injections) and after intake of 
QT-extending drugs or CYP3A4 inhibitors (a list of relevant drugs will be included in the Study 
MOP). 
9.4.6. 
Physical Examination 
A complete physical examination including all major body systems will be performed at 
Screening. At select subsequent study visits, an abbreviated review of systems will be performed 
to capture changes since Screening. 
Height, weight and BMI will be determined as described in Table 3.  
9.4.7. 
C-SSRS 
The Columbia Suicide Severity Rating Scale (C-SSRS) will be used to assess both behavior and 
ideation. The C-SSRS tracks all suicidal events, and provides a summary of suicidal ideation and 
behavior. It assesses the lethality of attempts and other features of ideation (frequency, duration, 
controllability, reasons for ideation, and deterrents), all of which are significantly predictive of 
completed suicide.  
Two versions of the C-SSRS will be used in this study: the Baseline/Screening version (6 months 
and lifetime history) and the Since Last Visit version. The Screening version of the C-SSRS will 
be administered at Screening. The Since Last Visit version of the C-SSRS will be administered at 
all subsequent assessment times, as indicated in Table 3. 
The C-SSRS is to be administered by the Investigator or his/her qualified designee. Qualified 
designee is defined as physician, osteopath, nurse practitioner, clinical psychologist or 
physician’s assistant, who is licensed and has completed the C-SSRS training within the last 2 
years. The survey should be administered by the same assessor, where possible, throughout the 
study. 


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9.4.8. 
Injection Site Examination  
CAM2038 injection sites will be examined during each scheduled visit for any signs of adverse 
site reactions, including erythema, pruritus, edema, pain, etc. If needed, a photograph of the 
adverse site reactions wil be taken and shared with the medical monitor for review. The pain 
scale will be completed by the subjects within 10 minutes after each injection. The new injection 
site will also be examined within 15 minutes after each injection to determine if any site related 
AEs have occurred. Injection site evaluation forms will be included in the Trial MOP. Subjects 
will also be queried specifically about local tolerability AEs in connection to the examinations. 
9.4.9. 
Psychosocial Counseling 
All subjects will receive drug counseling once monthly (at least once every four weeks). 
Additional counseling can be provided as clinically indicated; however, all additional counseling, 
visits or phone calls must be recorded. 
9.4.10. 
Treatment Identification Card 
Subjects will receive a wallet card indicating that they are receiving BPN as part of the study. 
This card should be presented to health care providers by the subject in the event of an 
emergency or if medications such as opioid analgesics are required (see Section 8.7). Sample 
wallet cards will be provided for IRB submission. 
9.4.11. 
Other Safety Considerations 
Buprenorphine may impair the mental and physical abilities required for performance of 
potentially dangerous tasks. Subjects will be instructed to avoid operating heavy machinery 
during induction, and to exercise caution in performing activities requiring alertness such as 
driving a car during the first few days after the beginning of the trial, or until such time that they 
are reasonably certain that their ability to engage in such activities is not adversely affected. 
9.5. 
Appropriateness of Measures 
Standard safety outcomes, such as AEs, ECG, vital signs and clinical laboratory testing will be 
assessed during the study.  
Given the open-label, uncontrolled nature of the study, the efficacy endpoints will be considered 
exploratory. These additional measures were selected as a series of measures and scales to 
provide an exploratory assessment of efficacy of CAM2038 q1w and q4w, including monthly 
urine toxicology with patient self-reported illicit opioid use, retention in treatment, Investigator- 
and subject-reported withdrawal and subject-reported cravings. Standard and widely used 
measures of withdrawal will be included in this study (COWS and SOWS) (Handelsman et al, 
1987; Wesson and Ling, 2003) in order to ensure that subject’s withdrawal symptoms are 
adequately controlled by CAM2038 q1w and q4w. Desire to Use and Need to Use VASs was 
selected versus typical Craving VAS because the latter term is ambiguous and may have different 
meaning to different individuals, while the Desire/Need to Use VAS more directly assesses  
the potential behavioral outcome (Kozlowski et al, 1989). 


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9.6. 
Safety Variables 
Safety variables include:  
§ AEs and SAEs 
§ Clinical laboratory tests 
§ ECG 
§ Vital signs 
§ Physical and injection site examinations 
§ Concomitant medications 
9.7. 
Efficacy Variables 
Efficacy variables include:  
§ Urine toxicology results for illicit opioids  
§ Self-reported illicit opioid use 
§ Retention (%) in treatment 
§ Work Productivity and Activity Impairment Questionnaire-General Health (WPAI-GH) 
§ EQ-5D-5L Health Questionnaire 
§ Patient Satisfaction Scale 
§ Measures of opioid withdrawal:  
o COWS 
o SOWS 
§ Measures of opioid craving:  
o Desire to Use VAS 
o Need to Use VAS 
§ Urine toxicology results for other drugs of abuse 
 


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10. 
DATA QUALITY ASSURANCE 
This study will be conducted under Good Clinical Practice (GCP) and all applicable regulatory 
requirements. To ensure compliance, the Sponsor or designee may conduct a quality assurance 
audit, as outlined in Section 10.2.  
Actions to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study centers; the review of protocol procedures with the 
Investigator and study personnel prior to study start; the design of suitable source documents 
with appropriate instructions for use (where applicable); the internal audit of source data 
according to GCP and internal procedures to ensure their accuracy, completeness, and 
verifiability; as well as the periodic site monitoring by the Sponsor. The Sponsor or designee will 
review source documents for accuracy and completeness during on-site monitoring visits and 
after their return to the Sponsor; any discrepancies will be resolved with the Investigator, as 
appropriate.  
Significant and/or repeated non-compliance will be investigated and remedial action instituted 
when appropriate. Failure to comply with remedial actions may result in investigational site 
termination and regulatory authority notification. 
10.1. 
Data Collection  
Source documents include but are not limited to original documents, data and records such as 
hospital/medical records (including electronic health records), clinic charts, lab results, 
participant diaries, data recorded in automated instruments, microfilm or magnetic media, and 
pharmacy records, etc. This study will use electronic data capture (EDC). At a minimum, all data 
required by the protocol should have supporting source documentation for entries in the EDC 
system. 
All CRFs will be completed by the site staff prior to review by the Sponsor’s monitor or 
designated representative. The Sponsor’s monitor or designated representative will review all 
source records on-site and compare them to the data collected on the CRF.  All entries, 
corrections, and alterations will be made by the Investigator or other authorized study personnel. 
All data entries will be verified for accuracy and correctness by independent monitors. The 
electronic data capture system maintains a full audit trail.  
10.2. 
Study Auditing and Monitoring 
Monitoring of the study site (including, but not limited to, reviewing CRFs for accuracy and 
completeness) will be performed by the Sponsor’s designated monitor(s). The extent, nature, and 
frequency of on-site visits will be based on such considerations as the study objectives and/or 
endpoints, the purpose of the study, study design complexity, and enrollment rate. By signing the 
protocol, the Investigator agrees that, within local regulatory restrictions and institutional and 
ethical considerations, authorized representatives of the Sponsor, a regulatory authority, and/or 
an IRB may visit the site to perform audits or inspections, including the drug storage area, study 


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drug stocks, drug accountability records, participant charts and source documents, and other 
records related to study conduct. The purpose of the Sponsor audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether the study-related activities were conducted, and data recorded, analyzed, and 
accurately reported according to the protocol, the site’s standard operating procedures, GCP 
guidelines of the ICH, and any applicable regulatory requirements. The Investigator should 
contact the Sponsor immediately if contacted by a regulatory agency regarding an inspection. 


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11. 
STATISTICAL METHODS AND DETERMINATION OF 
SAMPLE SIZE 
11.1. 
Statistical and Analytical Plans 
Complete details of the statistical analyses to be performed will be documented in the Study 
Statistical Analysis Plan (SAP), which will be completed prior to unlocking the database. This 
document will include more detail of analysis populations, summary strategies, and any 
amendments to the proposed analyses listed here, if necessary. Any changes to the SAP will be 
outlined in the final study report. 
11.2. 
Analysis Populations 
The study analysis populations will consist of: 
§ Full Exposure Safety Population: All subjects who have been exposed to CAM2038 for 
48 weeks 
§ Overall Safety Population: All subjects who received at least one CAM2038 treatment 
The safety results will be presented for both Full Exposure Safety Population and Overall Safety 
Population.  
11.3. 
Planned Analyses 
11.3.1. 
Demographics and Other Baseline Characteristics 
Disposition for all enrolled subjects will be summarized. Reasons for discontinuation will be 
tabulated. 
Demographic data and baseline psychosocial characteristics will also be summarized.  
Tabular summaries and/or listings will be provided for baseline clinical characteristics, such as 
illicit drug and treatment use history, medical and psychiatric history, inclusion/exclusion 
criteria, and medication history. 
11.3.2. 
Analysis of Efficacy Measures 
Exploratory efficacy measures will be summarized by visit using standardized descriptive 
statistics and listed by subject. 
11.3.3. 
Analysis of Safety Assessments 
Exposure and safety summaries will be presented for both Safety Populations.  
All AEs will be coded by primary system organ class (SOC) and preferred term according to the 
Medical Dictionary for Regulatory Activities (MedDRA), and summarized by number and 
percent of subjects in each primary SOC and preferred term. Summaries of these AE subsets will 


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be presented for relationship to study drug, intensity, seriousness, AEs or SAEs leading to 
discontinuation and AEs occurring in 5% or greater (by preferred term). Frequencies for deaths 
and hospitalizations will also be summarized. 
Data for clinical laboratory tests, ECG, vital signs, and physical and injection site examinations 
will be summarized using standard descriptive and change from baseline statistics. Shift tables 
and tabular summaries of abnormalities will be provided, where appropriate. Medications will be 
coded using the World Health Organization Drug dictionary and summarized using descriptive 
statistics.  
By-subject listings will be provided for all safety data. 
11.4. 
Determination of Sample Size 
A total of 100 subjects with at least 48 weeks of CAM2038 exposure will be needed for the 
safety assessments. Approximately 228 subjects will be enrolled initially into this study with an 
estimated dropout rate of approximately 50% to ensure a total of 100 subjects are exposed to 
CAM2038. Once a total of 100 subjects complete 48 weeks of CAM2038 treatment, the study 
will be completed.  


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HS-14-499  
CONFIDENTIAL 
 
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12. 
STUDY ADMINISTRATION AND INVESTIGATOR 
RESPONSIBILITIES 
Additional details may be outlined in the Clinical Study Agreement (CSA) between the sponsor 
and the investigational site.  
12.1. 
Regulatory and Ethical Considerations 
12.1.1. 
Ethical Conduct of the Study 
The Investigator will conduct the study in accordance with GCP and all applicable regulations, 
including, where applicable, the Declaration of Helsinki. The study will also be carried out in 
keeping with applicable national and local laws and regulations. This may include an inspection 
by the Sponsor’s representatives and/or regulatory authority’s representatives at any time. 
12.1.2. 
Ethics Approval 
The investigational site’s IRB must meet all relevant regulatory requirements. The study protocol 
and ICF will be reviewed by the IRB prior to enrolling participants into the study; written 
approval from the committee must be received by the sponsor before drug will be released to the 
Investigator.  The Investigator is responsible for submitting all protocol or ICF changes and SAE 
reports to the IRB according to local procedures. At a minimum, all SAEs requiring an 
investigational new drug safety report must be immediately reported. 
In accordance with applicable local regulatory requirements, the Investigator may be obligated to 
provide periodic safety updates on the conduct of the study at his or her research site and 
notification of study closure to the IRB. Such periodic safety updates and notifications are the 
responsibility of the Investigator and not of the Sponsor. The Sponsor will be provided with 
copies of all notifications sent to the IRB. 
All relevant correspondence from the IRB will be forwarded by the respective study site to the 
Sponsor in a timely fashion. 
12.1.3. 
Subject Informed Consent 
The Investigator (or authorized designee) will ensure that the participant (or the participant’s 
legal representative) is given full and adequate oral and written information about the nature, 
purpose, potential and possible risks and benefits of the study. Each prospective subject will 
receive an IRB-approved ICF that summarizes the pertinent study information and will be given 
ample time to read the form and ask questions about the study. All information is to be provided 
in a language understandable to the participant and must not include any language that waives 
the participant’s legal rights. Prospective participants must also be informed of their right to 
withdraw consent without prejudice at any time during the study. If the participant chooses to 
participate, he/she must sign the ICF before any study-related procedures are performed.  
Significant changes to the protocol or product safety information may require a revision of the 
ICF, which must be reviewed and signed by all applicable study participants. 


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CONFIDENTIAL 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 56 of 62 
The time that informed consent is obtained must be documented. The Investigator must maintain 
the original, signed ICF in the participant’s source documents. A copy of the signed ICF must be 
given to the study participant. 
12.2. 
Privacy and Confidentiality 
The Investigator is responsible for complying with applicable privacy regulations, per his or her 
jurisdiction. Only information identified in this protocol will be collected. The information 
collected will only be used for the purposes identified in this protocol. 
To ensure anonymity and to limit disclosure, participants will be assigned a unique identifier at 
their first assessment. This identifier will be cross-referenced in the participant’s chart. The 
identifier will not contain any potentially identifiable information. An identifier log will be 
maintained, linking each participant’s name to the corresponding identifier. This log will be 
stored at the research site in a secure location. 
The knowledge gained through this study is the property of the Sponsor. The Sponsor, 
representatives and affiliated companies of the Sponsor, the IRB, and regulatory agencies (such 
as the United States FDA) may inspect medical records related to the study to check the validity 
and accuracy of the data gathered in this study. Participant medical records (with participant’s 
initials and/or date of birth) may be copied. Confidentiality of participant records will be 
maintained except where release of information is required by law.  
The results of this study will be reported in such a manner that participants will not be 
identifiable in any way. Published reports or presentations will refer to grouped data or coded 
individual data and not to any identifiable individuals. Study reports sent to the Sponsor or drug 
regulatory agencies will not include participant names. 
By signing the ICF, the participant consents to the collection, access, use, and disclosure of his or 
her information as described in the ICF document. If a participant withdraws consent, some of 
the subject’s information may still be collected, used, and disclosed by those involved in this 
study, per applicable laws.  
By signing this protocol, the Investigator affirms that he or she will maintain in confidence 
information furnished to him or her by the Sponsor and will divulge such information to his or 
her respective IRB or IEC under an appropriate understanding of confidentiality with such board. 
All data will be considered the sole property of the Sponsor. Please refer to the Clinical Study 
Agreement (CSA) for details. 
12.3. 
Study and Site Closure 
Upon completion of the study, all study data will be provided to the Sponsor following review of 
site study records for completeness, and data clarifications and resolutions. Accounting, 
reconciliation, and final disposition of used and unused study drugs, treatment codes, and 
emergency code break envelopes will be performed, as applicable. 
In addition, the Sponsor reserves the right to temporarily suspend or prematurely discontinue this 
study at any time and for any reason. If such action is taken, the Sponsor will discuss this with 


Clinical Trial Protocol 
Braeburn Pharmaceuticals 
HS-14-499  
CONFIDENTIAL 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 57 of 62 
the Investigator (including the reasons for taking such action) at that time. The Sponsor will 
promptly inform any other investigators and/or institutions conducting the study, if the study is 
suspended or terminated for safety reasons and will inform the regulatory authorities of the 
suspension or termination of the study and the reason(s) for the action. If required by applicable 
regulations, the Investigator will inform the IRB promptly and provide the study participants 
with the reason for the suspension or termination. If the study is prematurely discontinued, all 
study data will be returned to the Sponsor.  
12.4. 
Regulatory Documents and Records Retention 
The Investigator is responsible for creating and/or maintaining all study documentation required 
by 21 CFR 50, 54, 56 and 312, ICH E6 section 8, as well as any other documentation defined in 
the protocol or CSA. The Investigator must provide key documents to the Sponsor prior to the 
start of the study.  A complete list of required regulatory documents will be supplied by the 
Sponsor or its representative. 
Federal and local regulations require that the Investigator retain a copy of all regulatory 
documents and records that support the data for this study for whichever of the following is the 
longest period of time: 
§ A period of 2 years following the final date of approval by the FDA or other regulatory 
agency of the study drug for the purposes that were the subject of the investigation; or 
§ A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation. 
The Sponsor will notify investigators once one of the above 2 timeframes has been satisfied. 
If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained for a period of 2 years 
following notification by the Sponsor that the entire clinical investigation (not merely the 
Investigator’s portion) is completed, terminated, or discontinued or 2 years following withdrawal 
of the Investigational New Drug application/Clinical Trial Authorization or request for marketing 
approval (New Drug Application/Marketing Authorization Application).  
If the Investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept the 
responsibility. The Sponsor must be notified in writing of the name and address of the new 
custodian. Study records should not be destroyed without consultation with the Sponsor. 
12.5. 
Delegation of Responsibilities and Adequate Resources 
The Investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study.  


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HS-14-499  
CONFIDENTIAL 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 58 of 62 
The term “Investigator” used throughout this protocol refers to the principal investigator and/or 
qualified sub-investigators. However, the Investigator may delegate responsibilities to other 
investigational site personnel. The Investigator shall delegate tasks only to individuals qualified 
by education, training and experience to perform the delegated tasks. The Investigator shall have 
direct oversight of all delegated activities and shall document delegation of responsibilities. The 
Investigator is responsible for ensuring all delegated staff has been properly trained on the 
protocol and their assigned study responsibilities. A delegation log identifying all delegated 
duties and the individual to whom they have been delegated will be maintained at the 
investigational site.  
12.6. 
Protocol Amendments 
Approval of a protocol amendment by the Investigator’s IRB must be obtained before 
implementation of the protocol amendment, unless a change is necessary to eliminate an 
apparent immediate hazard to the participant or when the change involves logistical or 
administrative aspects of the study. The protocol amendment must be signed and dated by both 
the Sponsor and the Investigator. The Sponsor or designee will submit protocol amendments to 
the appropriate regulatory authorities, if required. 
12.7. 
Financial Disclosure 
Clinical investigators are required to provide financial disclosure information for the submission 
of certification or disclosure statements required under 21 CFR § 54. As defined in 21 CFR § 
54.2, a clinical investigator is a listed or identified investigator or sub-investigator who is directly 
involved in the treatment or evaluation of research participants. The term also includes the 
spouse and each dependent child of the Investigator. In addition, investigators must promptly 
update financial disclosure information if any relevant changes occur during the course of the 
investigation and for 1 year following completion of the study. 


Clinical Trial Protocol 
Braeburn Pharmaceuticals 
HS-14-499  
CONFIDENTIAL 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 59 of 62 
13. 
SPONSOR APPROVAL PAGE 
An Open-Label Multicenter Study Assessing the Long-Term Safety of a Once-
Weekly and Once-Monthly, Long-Acting Subcutaneous Injection Depot of 
Buprenorphine (CAM2038) in Adult Outpatients with Opioid Use Disorder 
 
Version: 5.0 
Date: 09-Dec-2016 
 
 
 
 
 
 
 
Braeburn Pharmaceuticals 
Sonnie Kim, PharmD 
VP, Clinical Development & Medical Affairs 
 
09-Dec-2016 
Sponsor Representative 
Full Title 
 
Date 
(DD-MMM-YYYY) 
 


Clinical Trial Protocol 
Braeburn Pharmaceuticals 
HS-14-499  
CONFIDENTIAL 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 60 of 62 
14. 
INVESTIGATOR PROTOCOL AGREEMENT PAGE 
An Open-Label Multicenter Study Assessing the Long-Term Safety of a Once-
Weekly and Once-Monthly, Long-Acting Subcutaneous Injection Depot of 
Buprenorphine (CAM2038) in Adult Outpatients with Opioid Use Disorder 
 
Version: 5.0 
Date: 09-Dec-2016 
I have read this protocol and I agree to conduct the study in accordance with the protocol and 
with all applicable government regulations and International Conference on Harmonisation/Good 
Clinical Practice guidances. 
 
Principal Investigator’s 
Name 
 
(please print or type) 
 
 
 
 
Principal Investigator’s Signature 
 
Date (DD-MMM-YYYY) 


Clinical Trial Protocol 
Braeburn Pharmaceuticals 
HS-14-499  
CONFIDENTIAL 
 
 
 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 61 of 62 
 
15. 
REFERENCES 
• Johnson, R.E., J.H. Jaffe, and P.J. Fudala, A controlled trial of buprenorphine treatment 
for opioid dependence. Jama-Journal of the American Medical Association, 1992. 
267(20): p. 2750-2755. 
• Strain, E.C., et al., Comparison of Buprenorphine and Methadone in the treatment of 
Opioid dependence. American Journal of Psychiatry, 1994. 151(7): p. 1025-1030. 
• Schottenfeld, R.S., et al., Buprenorphine vs methadone maintenance treatment for 
concurrent opioid dependence and cocaine abuse. Archives of General Psychiatry, 1997. 
54(8): p. 713-720. 
• Ling, W., et al., Buprenorphine maintenance treatment of opiate dependence: a 
multicenter, randomized clinical trial. Addiction, 1998. 93(4): p. 475-486. 
• World Health Organization, United Nations Office on Drugs and Crime. Substitution 
maintenance therapy in the management of opioid dependence and HIV/AIDS 
prevention: position paper / UNAIDS, 2004, url: 
http://www.who.int/substance_abuse/publications/en/PositionPaper_English.pdf. 
• Chandler R, Fletcher B, Volkow N. Treating drug abuse in the criminal justice system: 
improving public health and safety. Journal of the American Medical Association; 2009: 
301, 183-190. 
• Winstock AR, Lea T, Sheridan J. Prevalence of diversion and injection of methadone and 
buprenorphine among clients receiving opioid treatment at community pharmacies in 
New South Wales, Australia. International Journal of Drug Policy 2008; 19: 450-458. 
• Food and Drug Administration Center for Drug Evaluation and Research (CDER) and 
Center for Biologics Evaluation and Research (CBER). Draft Guidance for Industry Non-
Inferiority Clinical Trials, March 2010. 
• Fals-Stewart W, O'Farrell TJ, Freitas TT, McFarlin SK, Rutigliano P. The timeline 
followback reports of psychoactive substance use by drug-abusing patients: psychometric 
properties. J Consult Clin Psychol. 2000;68:134–144. 
• Kozlowski LT1, Mann RE, Wilkinson DA, Poulos CX. "Cravings" are ambiguous: ask 
about urges or desires. Addict Behav. 1989;14(4):443-5. 
• Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new 
rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293-308.  


Clinical Trial Protocol 
Braeburn Pharmaceuticals 
HS-14-499  
CONFIDENTIAL 
 
 
 
 
Global Protocol Amendment 4: v5.0, 09-Dec-2016 
 
Page 62 of 62 
 
• Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive 
Drugs. 2003 Apr-Jun;35(2):253-9. 
• Reilly Associates. WPAI:GH. Accessed at: http://www.reillyassociates.net/WPAI_GH.html. 
Accessed on: June 14, 2016. 
• 
EuroQOL Group Association. EQ-5D-5L. Accessed at: http://www.euroqol.org/eq-5d-
products/eq-5d-5l.html. Accessed on: June 14, 2016. 

SAP_000.pdf: 
HS-14-499 
Phase III 
 
An Open-Label Multicenter Study Assessing the Long-Term Safety 
of a Once-Weekly and Once-Monthly, Long-Acting Subcutaneous 
Injection Depot of Buprenorphine (CAM2038) in Adult Outpatients 
with Opioid Use Disorder 
 
Statistical Analysis Plan (SAP) 
 
 
Sponsor 
BRAEBURN PHARMACEUTICALS 
47 Hulfish Street, Suite 441 
Princeton, NJ 08542 
Tel: (609) 751-5375 
Fax: (609) 921-2156 
 
 
Version 1.01 
 
20 April 2017 
 
 
 


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SPONSOR APPROVAL 
 
The undersigned have reviewed the format and content of this prospective statistical analysis plan (SAP) 
and have approved it for use to analyze the HS-14-499 data. 
 
 
BRAEBURN PHARMACEUTICALS  
 
 
 
Sonnie Kim, Pharm. D. 
 
 
 
 
 
20 Apr 2017 
 
 
 
 
 
Print Name 
 
Signature 
 
Date 
 
 
 
STATISTICIAN 
 
Michael Chen, Ph.D. 
 
 
 
20 Apr 2017 
 
 
 
 
 
Print Name 
 
Signature 
 
Date 


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TABLE OF CONTENTS 
1.0	  
DOCUMENT	  HISTORY	  ...........................................................................................................................	  5	  
2.0	  
LIST	  OF	  ABBREVIATIONS	  ....................................................................................................................	  5	  
3.0	  
INTRODUCTION	  ......................................................................................................................................	  6	  
4.0	  
STUDY	  DESCRIPTION	  ............................................................................................................................	  6	  
4.1	  
Study	  Objectives	  ......................................................................................................................	  6	  
4.2	  
Study	  Treatments	  ....................................................................................................................	  6	  
4.3	  
Study	  Design	  ..............................................................................................................................	  6	  
4.4	  
Randomization	  and	  Blinding	  ...............................................................................................	  7	  
5.0	  
ANALYSIS	  POPULATIONS	  ....................................................................................................................	  7	  
5.1	  
Overall	  Safety	  Population	  .....................................................................................................	  7	  
5.2	  
Full	  Exposure	  Safety	  Population	  ........................................................................................	  7	  
5.3	  
Efficacy	  Population	  .................................................................................................................	  7	  
6.0	  
GENERAL	  CONVENTIONS	  .....................................................................................................................	  7	  
6.1	  
Definition	  of	  Baseline	  .............................................................................................................	  8	  
6.2	  
Software	  ......................................................................................................................................	  8	  
6.3	  
Changes	  to	  Planned	  Analyses	  ..............................................................................................	  8	  
7.0	  
SAMPLE	  SIZE	  ............................................................................................................................................	  8	  
8.0	  
DESCRIPTION	  OF	  THE	  STUDY	  POPULATIONS	  ..............................................................................	  8	  
8.1	  
Disposition	  .................................................................................................................................	  8	  
8.2	  
Demographic	  and	  Baseline	  Characteristics	  ....................................................................	  8	  
8.3	  
Medical	  History	  ........................................................................................................................	  9	  
9.0	  
PRIOR	  AND	  CONCOMITANT	  MEDICATIONS	  ..................................................................................	  9	  
10.0	  
EFFICACY	  ANALYSES	  .............................................................................................................................	  9	  
10.1.1	   Efficacy	  Variables	  .......................................................................................................................	  9	  
10.1.2	   Urine	  Toxicology	  Results	  for	  Illicit	  Opioids	  .................................................................	  10	  
10.1.3	   Self-­‐‑reported	  Illicit	  Opioid	  Use	  .........................................................................................	  10	  
10.1.4	   Retention	  in	  Treatment	  ........................................................................................................	  10	  
10.1.5	   Retention	  in	  Study	  ..................................................................................................................	  10	  
10.1.6	   Measures	  of	  Opioid	  Withdrawal	  .......................................................................................	  10	  
10.1.7	   Measures	  of	  Opioid	  Craving	  ...............................................................................................	  11	  
10.1.8	   Urine	  Toxicology	  Results	  for	  Other	  Drugs	  of	  Abuse	  ................................................	  11	  
10.1.9	   Work	  Productivity	  and	  Activity	  Impairment	  Questionnaire	  General	  Health	  
(WPAI-­‐‑GH)	  .................................................................................................................................	  11	  
10.1.10	  EQ-­‐‑5D-­‐‑5L	  Health	  Questionnaire	  .......................................................................................	  11	  
10.1.11	  Patient	  Satisfaction	  Scale	  .....................................................................................................	  11	  
11.0	  
SUMMARIES	  OF	  MEASURES	  OF	  SAFETY	  ........................................................................................	  11	  
11.1.1	   Extent	  of	  Exposure	  .................................................................................................................	  11	  
11.1.2	   Adverse	  Events	  ........................................................................................................................	  12	  


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11.1.3	   Laboratory	  Assessments	  .....................................................................................................	  12	  
11.1.4	   Vital	  Signs	  ...................................................................................................................................	  13	  
11.1.5	   Physical	  Examination	  ............................................................................................................	  13	  
11.1.6	   12-­‐‑Lead	  Electrocardiogram	  ...............................................................................................	  13	  
11.1.7	   Injection	  Site	  Examination	  ..................................................................................................	  13	  
11.1.8	   C-­‐‑SSRS	  ..........................................................................................................................................	  13	  
12.0	  
IDENTIFICATION	  AND	  SUMMARY	  OF	  PROTOCOL	  DEVIATIONS	  ...........................................	  13	  
13.0	  
DATA	  QUALITY	  ASSURANCE	  ............................................................................................................	  14	  
14.0	  
REFERENCES	  ..........................................................................................................................................	  14	  
15.0	  
APPENDICES	  ..........................................................................................................................................	  14	  
15.1	  
Appendix	  A	  -­‐‑	  List	  of	  Tables,	  Listings,	  and	  Figures	  ......................................................	  14	  
15.2	  
Appendix	  B	  -­‐‑	  Imputation	  Algorithm	  for	  Partial	  and	  Missing	  Dates	  ......................	  20	  
 


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1.0  
DOCUMENT	  HISTORY	  
Version 
Date  
Changes made since previous version 
1.00 
25 January 2017 
Final  
 
1.01 
20 April 2017 
Updates on the sample size and inclusion of separate analysis of 
subjects new to treatment. 
 
2.0  
LIST	  OF	  ABBREVIATIONS	  
Abbreviation 
Definition 
AE 
Adverse Event 
BPN 
Buprenorphine or Buprenorphine/Naloxone 
COWS 
Clinical Opiate Withdrawal Scale 
CRF 
Case Report Form (may include electronic data capture systems or paper forms) 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
ECG 
Electrocardiogram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
PT 
MedDRA Preferred Term 
SAE  
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard Deviation 
SL 
Sublingual 
SOC 
MedDRA System Organ Class 
SOWS 
Subjective Opiate Withdrawal Scale 
TEAE 
Treatment-Emergent Adverse Event 
VAS 
Visual Analogue Scale 
WPAI-GH 
Work Productivity and Activity Impairment Questionnaire General Health 
 


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3.0  
INTRODUCTION	  
This statistical analysis plan (SAP) is based on Protocol HS-14-499, Version 3.0, dated 18-Nov-2016. 
The purpose of this document is to provide details on study populations and on how the variables will be 
derived, how missing data will be handled, as well as details on statistical methodologies to be used to 
analyze the safety and efficacy data from the study.   
 
The document may evolve over time, for example, to reflect the requirements of protocol amendments or 
regulatory requests. However, the final SAP must be finalized, approved by the Sponsor, and placed on 
file before the database is locked and treatment codes are unblinded. Deviations from the approved plan 
will be noted in the clinical study report. 
4.0  
STUDY	  DESCRIPTION	  
4.1  
STUDY	  OBJECTIVES	  
Primary Objective: To demonstrate the safety and tolerability of CAM2038 products in 12-month 
(48-week) buprenorphine (BPN) treatment in adult outpatients with opioid use disorder. 
 
Secondary Objectives: To evaluate efficacy of CAM2038 through several efficacy parameters, including 
urine toxicology, signs and symptoms of withdrawal and cravings in adult outpatients with opioid use 
disorder.  
4.2  
STUDY	  TREATMENTS	  	  
Following Screening, qualified patients will be initiated on either CAM2038 q1w or q4w, based on their 
current treatment status (qualified patients currently on sublingual (SL) BPN or seeking BPN treatment).  
Qualified patients will be initiated or transitioned to CAM2038 q1w or q4w as follows: 
 
•  
Initiation of BPN treatment – initiate with CAM2038 q1w  
•  
Currently receiving SL BPN treatments – transfer to corresponding CAM2038 q1w or q4w dose 
 
Patients will be allowed to receive supplemental BPN during the study with booster SC injections of 
CAM2038 q1w 8 mg up to a maximum dose of 40 mg CAM2038q1w per week. For patients on 
CAM2038 q4w, a maximum of two booster doses of CAM2038 q1w 8 mg SC injections may be given 
per week. Dose adjustments (up or down titrations) will also be allowed at scheduled visits.  
4.3  
STUDY	  DESIGN	  
This is an open-label multi-center, 12-month safety study, consistent with standard practice for long-term 
safety studies. This one-year safety study will utilize CAM2038 q1w (once weekly) and CAM2038 q4w 
(once monthly) and will have 3 phases: Screening, Treatment, and Follow-up.   
 
Patients who are currently taking SL BPN (weekly or monthly prescription visits) or individuals who are 
actively seeking BPN treatment but who have not yet begun a treatment regimen, may be eligible for the 
study.  
 


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Following Screening, qualified patients will be initiated on either CAM2038 q1w or CAM2038 q4w and 
receive study treatment as described in Section 4.3.  
 
The study will end when at least 100 patients have been exposed to CAM2038 for 12 months (48 weeks). 
All patients will be transitioned back to usual care and followed for an additional 4 weeks (up to 
Week 53).  
4.4  
RANDOMIZATION	  AND	  BLINDING	  
This is an open-label study.  
5.0  
ANALYSIS	  POPULATIONS	  
5.1  
OVERALL	  SAFETY	  POPULATION	  
All patients who received at least one dose of CAM2038. 
5.2  
FULL	  EXPOSURE	  SAFETY	  POPULATION	  
All patients who have been exposed to CAM2038 for 48 weeks. 
5.3  
EFFICACY	  POPULATION	  
In addition to the protocol-specified populations, the efficacy population will include all patients who 
have received at least one dose of CAM2038 and have provided some post-baseline efficacy 
measurements.   
6.0  
GENERAL	  CONVENTIONS	  
Unless otherwise stated, all analyses will be performed using SAS Version 9 and all hypothesis tests will 
be conducted at a two-sided significance level of 0.05. P-values will be presented with 3 decimals and p-
values that are less than 0.001 will be presented as <0.001. 
 
Continuous (non-survival-related) data will be summarized using descriptive statistics: number of 
observations (n), mean, standard deviation (SD), median, minimum, and maximum. Frequencies and 
percentages will be used to summarize categorical (discrete) data.  Presentations of categorical data will 
generally suppress percentages for items where the count is zero in order to draw attention to the nonzero 
counts.  In general, mean, standard deviation, median, minimum, maximum, and percentages will be 
presented with one decimal. 
 
Unless otherwise stated, confidence intervals, when presented, will be constructed at the two-sided 95% 
level.  For binomial variables, the 95% confidence intervals will be constructed using the normal 
approximation without continuity correction. 
 
Data listings will present all data collected on case report forms (CRFs) by study drug, center, and patient 
number.   


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6.1  
DEFINITION	  OF	  BASELINE	  
Unless otherwise stated, the last observed measurement before the first dose of CAM2038 will be 
considered the baseline measurement. If multiple observations are made during baseline, the baseline will 
be defined as average of the observations obtained during the baseline phase. 
6.2  
SOFTWARE	  
Most analyses will be conducted using SAS Version 9.2 or higher.   
6.3  
CHANGES	  TO	  PLANNED	  ANALYSES	  
Draft versions of the SAP will be numbered sequentially as Version 0.0i. The final approved version will 
be numbered as Version 1.00. Revisions after the “Final” version will be numbered as Version 1.0x. The 
clinical study report will document any changes made after the final version approved before database 
lock. 
7.0  
SAMPLE	  SIZE	  
A total of 100 patients with at least 48 weeks of CAM2038 exposure will be needed for the safety 
assessments. Approximately 228 patients will be enrolled initially into this study with an estimated drop-
out rate of 50% to ensure a total of 100 patients are exposed to CAM2038. Originally, the study was to 
end when at least 100 subjects had been exposed to CAM2038 for 12 months (48 weeks). However, a 
decision was made to allow all enrolled subjects to complete the entire treatment period and to not end the 
study after at least 100 subjects had completed 48 weeks of treatment.    
8.0  
DESCRIPTION	  OF	  THE	  STUDY	  POPULATIONS	  
All tables, figures, and listings must include a population descriptor (e.g., pre-defined populations: overall 
safety population, full exposure safety population and efficacy population) in the title. 
8.1  
DISPOSITION	  
Patient disposition summaries will be presented and will include the number of patients enrolled, the 
number and percentage of enrolled patients in each of the pre-defined populations, as well as the number 
and percentage of patients who complete the study.  The summaries will also include the reasons for early 
discontinuation from the study.   
 
Disposition summaries will be presented for each of the pre-defined populations separately. 
8.2  
DEMOGRAPHIC	  AND	  BASELINE	  CHARACTERISTICS	  
A summary of demographics and baseline characteristics will be presented for each of the pre-defined 
populations.  The demographic characteristics will consist of age, sex, ethnicity, and race using 
descriptive statistics. 
 
Demographic data including age, race, ethnicity, and gender, as well as baseline clinical characteristics 
will be summarized. Age will be calculated based on the following conditional algorithm:  
 
•  
Has the patient had his/her birthday this year? 


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o   Yes, then AGE = (year of informed consent) – (year of birth). 
o   No, then AGE = (year of informed consent) – (year of birth) – 1. 
 
Clinical baseline characteristics summarized will include, if available, weight, body mass index, region 
(Europe, the US and Australia), type of primary opioid use, years of drug use, when first diagnosed with 
opioid dependence, proportion of patients previously treated for opioid dependence and duration of 
buprenorphine treatment.  
8.3  
MEDICAL	  HISTORY	  
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
Medical history will be summarized and listings will be presented.   
9.0  
PRIOR	  AND	  CONCOMITANT	  MEDICATIONS	  
All medications recorded on the CRFs will be coded using the WHO DRUG Dictionary. Prior and 
concomitant medications will be summarized by anatomical therapeutic chemical (ATC) Class Level 4 
and WHO Drug base substance preferred name. 
 
Prior medications are defined as medications with stop dates occurring before the date of the first 
administration of any study treatment component. Concomitant medications are defined as medications 
with start dates occurring on or after the date of the first administration of any study treatment component 
and no more than 30 days after the last administration of any study treatment component. Medications 
with start and stop dates that bracket the date of the first administration of any study treatment component 
will be summarized as both prior and concomitant medications. 
 
Medications that clearly stopped prior to date of the first administration of any study treatment component 
will be included in the prior medications table, and medications that clearly started on or after date of the 
first administration of any study treatment component will be included in the concomitant medications 
table. All other medications will be included in both the prior and concomitant medications tables. 
 
Prior and Concomitant medication will be summarized for the safety populations. 
10.0   EFFICACY	  ANALYSES	  
10.1.1  EFFICACY	  VARIABLES	  
This is a long-term safety study and efficacy evaluation is not the primary objective of the study. All 
efficacy variables will be summarized using the efficacy population. The efficacy variables will include 
the following: 
 
•  
Urine toxicology results for illicit opioids  
•  
Self-reported illicit opioid use  
•  
Retention (%) in treatment (identical to exposure) 
•  
Retention (%) in study 
•  
Measures of opioid withdrawal:  
o   Clinical Opiate Withdrawal Scale (COWS) 
o   Subjective Opiate Withdrawal Scale (SOWS) 


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•  
Measures of opioid craving: 
o   Desire to Use Visual Analogue Scale (VAS)  
o   Need to Use VAS 
•  
Urine toxicology results for other drugs of abuse 
•  
Work Productivity and Activity Impairment Questionnaire General Health (WPAI-GH) 
•  
EQ-5D-5L Health Questionnaire 
•  
Patient Satisfaction Scale 
10.1.2  URINE	  TOXICOLOGY	  RESULTS	  FOR	  ILLICIT	  OPIOIDS	  
Percentage of patients with urine samples negative for illicit opioids (with and without self-reports of 
illicit opioid use) will be presented by week and month. Mean percentage of urine samples negative for 
illicit opioids (with and without self-reports of illicit opioid use) will also be presented. Additionally, 
mean urine samples negative for illicit opioids (with and without self-reports) will be presented by week 
and month separately for those subjects who were new to treatment upon entry into the study.  Due to the 
flexible visit schedule, no imputation of missing data will be applied.  
10.1.3  SELF-­‐‑REPORTED	  ILLICIT	  OPIOID	  USE	  
Percentage of patients reporting no illicit opioid use will be presented by week and month. Mean 
percentage of reports of no illicit opioid use will also be presented. Due to the flexible visit schedule, no 
imputation of missing data will be applied. 
10.1.4  RETENTION	  IN	  TREATMENT	  
Duration of treatment is defined as the time from the first dose of CAM2038 to the last dose plus 28 days 
if the last treatment was CAM2038 q4w or plus 7 days if the last treatment was CAM2038 q1w.  
 
Duration of treatment will be summarized by the percentage of patients retained in treatment by week. 
Data will also be presented using Kaplan-Meier plots.  
10.1.5  RETENTION	  IN	  STUDY	  
Duration in study is defined as the time from first dose of CAM2038 to the date of study discontinuation.  
 
Duration in study will be summarized by the percentage of patients retained in the study by week. Data 
will also be presented using Kaplan-Meier plots.  
10.1.6  MEASURES	  OF	  OPIOID	  WITHDRAWAL	  
Measures of withdrawal include COWS and SOWS. The COWS is comprised of 11 items, each with a 
score of 0 through 4 or 5. Higher scores are associated with greater withdrawal symptoms. The items are 
meant to be objective measures of a patient’s withdrawal symptoms (e.g., resting pulse rate). The SOWS 
is comprised of 16 items each with a score of 0 through 4. Higher scores are associated with greater 
withdrawal symptoms. The items are statements that are evaluated by the patient and are therefore 
subjective (e.g., I feel anxious, 0 = not at all, 1 = a little, 2 = moderately, 3 = quite a bit, 4 = extremely).  
 
If there are >=3 (i.e., >=20%) missing items in the COWS scale at a given visit or >=4 (i.e., >20%) 
missing items in the SOWS scale at a given visit, the COWS/SOWS score for that visit will be missing. If 
there are 1 or 2 missing items for the COWS assessment then the total of the non-missing items will be 
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for that visit. If 3 or fewer items are missing for the SOWS score then the total of the non-missing items 
will be calculated and the product of the calculated total and 16/(16 - # missing) will be used for the 
SOWS score.  
 
COWS and SOWS data will be presented by visit. Data will also be presented as change from baseline by 
subtracting the baseline values from the post-baseline values. Negative changes are thus indicative of 
improvement.  
10.1.7  MEASURES	  OF	  OPIOID	  CRAVING	  
Measures of craving include Desire to Use VAS and Need to Use VAS and will be assessed using 
unipolar 100 mm VAS; “Since your last scheduled assessment visit, indicate your worst or strongest 
desire/need to use opioids between 0 = No desire/need to use and 100 = Maximum desire/need to use on 
this scale”.  
 
VAS data for Desire to Use and Need to Use will be presented by visit. Data will also be presented as 
change from baseline by subtracting the baseline values from the post-baseline values. Negative changes 
are thus indicative of improvement. 
10.1.8  URINE	  TOXICOLOGY	  RESULTS	  FOR	  OTHER	  DRUGS	  OF	  ABUSE	  
Percentage of patients with urine samples positive for other drugs of abuse will be presented by week and 
month. Mean percentage of urine samples positive for other drugs of abuse will also be presented. Due to 
the flexible visit schedule, no imputation of missing data will be applied.  
10.1.9  WORK	  PRODUCTIVITY	  AND	  ACTIVITY	  IMPAIRMENT	  QUESTIONNAIRE	  
GENERAL	  HEALTH	  (WPAI-­‐‑GH)	  
Data	  for	  WPAI-­‐‑GH	  will	  be	  presented	  by	  item	  over	  time.	  	  
10.1.10  
EQ-­‐‑5D-­‐‑5L	  HEALTH	  QUESTIONNAIRE	  
Data for EQ-5D-5L will be presented over time.  
10.1.11  
PATIENT	  SATISFACTION	  SCALE	  
Patient satisfaction scale scores will be presented by item over time.  
11.0   SUMMARIES	  OF	  MEASURES	  OF	  SAFETY	  
Safety analyses will be performed for the overall safety population and full exposure safety population.   
 
Safety evaluations will be based on the incidence, intensity and type of adverse events (AEs), as well as 
on clinically significant changes in the patient’s vital signs, electrocardiogram (ECG), clinical laboratory 
results and injection site examinations. 
11.1.1  EXTENT	  OF	  EXPOSURE	  
Summary statistics (number and percentage) of weeks of exposure to study drug (i.e. from the date of the 
first injection to the date of the last injection plus 28 days if the last treatment was CAM2038 q4w or plus 
7 days if the last treatment was CAM2038 q1w) will be presented. Number of patients, number of 


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injections and exposure years will be presented by dose, treatment (CAM2038 q1w and CAM2038 q4w) 
and in total.  
11.1.2  ADVERSE	  EVENTS	  
Each AE and serious adverse event (SAE) term recorded on the CRFs by primary system organ class 
(SOC) and will be mapped to a preferred term (PT) using the MedDRA dictionary. The Investigator will 
assess AE severity and relationship to the study treatment. 
 
A treatment-emergent adverse event (TEAE) is defined as any AE with an onset date on or after the date 
of the first study treatment, or any ongoing event started on the date of the first dose that worsens in 
severity. Only AEs with an onset date prior to the date of the last dose + 30 days will be tabulated in 
summary tables. For the purpose of calculating treatment emergence and inclusion in summary tables, 
incomplete onset dates will be imputed as detailed in Appendix B.   
 
AEs will be summarized by the number and percent of patients in each primary SOC and PT. Patients will 
be counted only once for each primary SOC and each PT. Summary tables of AEs by primary SOC, PT 
and intensity will be provided. If a patient has more than one AE coded to the same PT, the patient will be 
counted only once for that PT by using the event with the highest intensity. Similarly, if a patient has 
more than one AE within a primary SOC category, the patient will be counted only once in that SOC 
category by using the event with the highest intensity. AEs by primary SOC, PT and relationship to study 
drug will be provided as well. If a patient has more than one AE coded to the same PT, the patient will be 
counted only once for that PT by using the most related event. Similarly, if a patient has more than one 
AE within a primary SOC category, the patient will be counted only once in that primary SOC category 
by using the most related event. In addition, SAEs by primary SOC and PT will be provided. Deaths and 
SAEs will be summarized similarly to AEs. All AE tables will also include the total number of events, 
counting multiple events per patient. 
 
Injection-related AEs, other (non-injection related) AEs as well as all AEs will be presented. Summaries 
of these AE subsets will be presented for the following categories: 
•  
Study drug-related 
•  
Intensity 
•  
Serious 
•  
AEs which led to treatment/study discontinuation 
•  
SAEs which led to treatment/study discontinuation 
•  
AEs occurring in 5% or greater of patients (by preferred term) 
 
In the AE summary, the SOCs and the PTs within each SOC will appear in descending order of 
frequency.   
 
Frequencies of deaths and hospitalizations will also be summarized. 
Other safety analyses will be performed as appropriate 
11.1.3  LABORATORY	  ASSESSMENTS	  
Chemistry, hematology, urinalysis and coagulation profile will be assessed at baseline and over time.  
Summary statistics for these parameters will be presented by visit for the actual value and change from 
baseline for each test in each laboratory category (hematology, chemistry, urinalysis, and coagulation 
profile). Shift tables will be presented for shifts from baseline lab categories to end of study laboratory 


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category.  The three laboratory categories will be:  L (below lower bound of normal range), N (within 
normal range), and H (above higher bound of normal range).    
If a lab value is reported using a non-numeric qualifier (e.g., less than (<) a certain value, or greater than 
(>) a certain value), the given numeric value will be used in the summary statistics, ignoring the non-
numeric qualifier. 
If a patient has repeated laboratory values for a given time point, the value from the first evaluation at that 
time point will be used for summarization purposes. For the purpose of determining baseline, the last non-
missing observation on or prior to first dose of CAM2038.   
11.1.4  VITAL	  SIGNS	  
Vital signs will be assessed over time. Vital sign values and change from baseline in the vital signs will 
be summarized. 
11.1.5  PHYSICAL	  EXAMINATION	  
Physical examination data at Screening will be summarized. 
11.1.6  12-­‐‑LEAD	  ELECTROCARDIOGRAM	  
12-Lead ECGs will be assessed over time. The ECG variables will include ventricular heart rate and the 
PR, QRS, QT, QTcB and QTcF intervals. The ECGs will be signed and dated by a medically-qualified 
individual to confirm review of the ECG and verify whether any abnormalities are clinically significant.  
 
Number and percent of patients in each ECG finding category (normal, abnormal not clinically 
significant, and abnormal and clinically significant), will be summarized for each visit. Summary 
statistics will be presented for the actual value and change for each ECG parameter. 
 
The number and percent of patients with QT, QTcB and QTcF intervals < 450 msec, 450 to <480, 480 to 
<500 and greater than/equal to 500 msec at each visit and overall (at any visit) will be summarized. 
Additionally, the number and percentage of patients with increases in these parameters of <30 msec, 30 to 
<60 msec and greater than/equal to 60 msec will be summarized at each visit.  
11.1.7  INJECTION	  SITE	  EXAMINATION	  
The injection site will be visually inspected for evidence of erythema, edema, itching, pain, infection, 
bleeding, abnormal healing and any other abnormalities.   
 
AEs that are believed to be associated with injection procedures will be summarized similarly to the 
summaries for other AEs (not associated with injection procedures). 
11.1.8  C-­‐‑SSRS	  
Data on Columbia-Suicide Severity Rating Scale (C-SSRS) will be summarized over time.  
12.0   IDENTIFICATION	  AND	  SUMMARY	  OF	  PROTOCOL	  DEVIATIONS	  
Major protocol deviations from entry criteria and treatment compliance will be summarized as far as they 
can be extracted from numeric or coded study data. 


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13.0   DATA	  QUALITY	  ASSURANCE	  
Accurate and reliable data collection will be ensured by verification and cross check of the CRFs against 
the investigator’s records by the study monitor (source document verification) and by the maintenance of 
a drug–dispensing log by the investigator.  Collected data will be entered into a computer database and 
subject to electronic and manual quality assurance procedures. 
14.0   REFERENCES	  
Not	  applicable.	  
15.0   APPENDICES	  
15.1   APPENDIX	  A	  -­‐‑	  LIST	  OF	  TABLES,	  LISTINGS,	  AND	  FIGURES	  	  
List of Tables 
Number 
Title 
TABLE 14.1.1.1 
Disposition of Enrolled Patients (Overall Safety Population) 
TABLE 14.1.1.2 
Disposition of Enrolled Patients (Full Exposure Safety Population) 
TABLE 14.1.1.3 
Disposition of Enrolled Patients (Efficacy Population) 
TABLE 14.1.2.1 
Demographics (Overall Safety Population) 
TABLE 14.1.2.2 
Demographics (Full Exposure Safety Population) 
TABLE 14.1.2.3 
Demographics (Efficacy Population) 
TABLE 14.1.3.1 
Baseline Clinical Characteristics (Overall Safety Population) 
TABLE 14.1.3.2 
Baseline Clinical Characteristics (Full Exposure Safety Population) 
TABLE 14.1.3.3 
Baseline Clinical Characteristics (Efficacy Population) 
TABLE 14.1.4.1 
Summary of Psychiatric History (Overall Safety Population) 
TABLE 14.1.4.2 
Summary of Psychiatric History (Full Exposure Safety Population) 
TABLE 14.1.4.3 
Summary of Psychiatric History (Efficacy Population) 
TABLE 14.1.5.1.1 
Prior Medications (Overall Safety Population) 
TABLE 14.1.5.1.2 
Prior Medications (Full Exposure Safety Population) 
TABLE 14.1.5.1.3 
Prior Medications (Efficacy Population) 
TABLE 14.1.5.2.1 
Concomitant Medications (Overall Safety Population) 
TABLE 14.1.5.2.2 
Concomitant Medications (Full Exposure Safety Population) 
TABLE 14.1.5.2.3 
Concomitant Medications (Efficacy Population) 
TABLE 14.1.6.1 
Substance Abuse Treatment History (Overall Safety Population) 
TABLE 14.1.6.2 
Substance Abuse Treatment History (Full Exposure Safety Population) 
TABLE 14.1.6.3 
Substance Abuse Treatment History (Efficacy Population) 
TABLE 14.2.1.1 
Summary of Urine Toxicology Results for Illicit Opioid Use Supported by Self-
Reported Illicit Opioid Use over Time (Efficacy Population) 
TABLE 14.2.1.2 
Summary of Urine Toxicology Results for Illicit Opioid Use Without Self-
Reported Illicit Opioid Use over Time (Efficacy Population) 
TABLE 14.2.2.1 
Summary of Mean Percentage of Urine Toxicology Results for Illicit Opioid Use 
Supported by Self-Reported Illicit Opioid Use (Efficacy Population) 
TABLE 14.2.2.2 
Summary of Mean Percentage of Urine Toxicology Results for Illicit Opioid Use 


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Without Self-Reported Illicit Opioid Use (Efficacy Population) 
TABLE 14.2.2.3 
Summary of Mean Percentage of Urine Toxicology Results for Illicit Opiiods 
Use Supported by Self-Reported Illicit Opioid Use by Treatmentment Status at 
Baseline (New to Treatment [Yes/No]) 
TABLE 14.2.2.4 
Summary of Mean Percentage of Urine Toxicology Results for Illicit Opioid Use 
Without Self-Reported Illicit Opioid Use by Treatment Status at Baseline (New 
to Treatment [Yes/No]) (Efficacy Population) 
TABLE 14.2.3.1 
Summary of Self-Reported Illicit Opioid Use over Time (Efficacy Population) 
TABLE 14.2.3.2 
Summary of Mean Percentage of Self-Reported Illicit Opioid Use (Efficacy 
Population) 
TABLE 14.2.4.1 
Summary of Retention (%) in Treatment over Time (Efficacy Population) 
TABLE 14.2.4.2 
Time to End of Retention in Treatment (Efficacy Population) 
TABLE 14.2.5.1 
Summary of Retention (%) in Study over Time (Efficacy Population) 
TABLE 14.2.5.2 
Time to End of Retention in Study (Efficacy Population) 
TABLE 14.2.4.3 
Summary of Retention (%) in Treatment over Time by Treatment Status at 
Baseline (New to Treatment [Yes/No]) (Efficacy Population) 
TABLE 14.2.4.4 
Time to End of Retention in Treatment by Treatment Status at Baseline (New to 
Treatment [Yes/No]) (Efficacy Population) 
TABLE 14.2.6 
Summary of Clinical Opiate Withdrawal Scale (COWS) over Time (Efficacy 
Population) 
TABLE 14.2.7 
Summary of Subjective Opiate Withdrawal Scale (SOWS) over Time (Efficacy 
Population) 
TABLE 14.2.8 
Summary of Desire to Use VAS over Time (Efficacy Population) 
TABLE 14.2.9 
Summary of Need to Use VAS over Time (Efficacy Population) 
TABLE 14.2.10.1 
Summary of Urine Toxicology Results for Other Drugs of Abuse over Time 
(Efficacy Population) 
TABLE 14.2.10.2 
Summary of Mean Percentage of Urine Toxicology Results for Other Drugs of 
Abuse (Efficacy Population) 
TABLE 14.2.11 
Summary of Work Productivity and Activity Impairment Questionnaire General 
Health (WPAI-GH) by Item over Time (Efficacy Population) 
TABLE 14.2.12 
Summary of EQ-5D-5L Health Questionnaire Data over Time (Efficacy 
Population) 
TABLE 14.2.13 
Summary of Patient Satisfaction Scale Scores by Item over Time (Efficacy 
Population) 
TABLE 14.3.1.1 
Summary of CAM2038 Exposure over Time (Overall Safety Population) 
TABLE 14.3.1.2 
Summary of CAM2038 Exposure over Time (Full Exposure Safety Population) 
TABLE 14.3.1.3 
Summary of CAM2038 Exposure by Dose and Number of Injections (Overall 
Safety Population) 
TABLE 14.3.1.4 
Summary of CAM2038 Exposure by Dose and Number of Injections (Full 
Exposure Safety Population) 
TABLE 14.3.2.1 
Summary of All Adverse Events by System Organ Class, Preferred Term, and 
Relationship (Overall Safety Population) 
TABLE 14.3.2.2 
Summary of All Adverse Events by System Organ Class, Preferred Term, and 
Relationship (Full Exposure Safety Population) 
TABLE 14.3.2.3 
Summary of All Injection-Related Adverse Events by System Organ Class, 
Preferred Term, and Relationship (Overall Safety Population) 
TABLE 14.3.2.4 
Summary of All Injection-Related Adverse Events by System Organ Class, 


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Preferred Term, and Relationship (Full Exposure Safety Population) 
TABLE 14.3.2.5 
Summary of All Injection-Related Adverse Events by Preferred Term, Time to 
Onset and Duration (Overall Safety Population) 
TABLE 14.3.2.6 
Summary of All Injection-Related Adverse Events by Preferred Term, Time to 
Onset and Duration (Full Exposure Safety Population) 
TABLE 14.3.2.7 
Summary of All Non-Injection Related Adverse Events by System Organ Class, 
Preferred Term, and Relationship (Overall Safety Population) 
TABLE 14.3.2.8 
Summary of All Non-Injection Related Adverse Events by System Organ Class, 
Preferred Term, and Relationship (Full Exposure Safety Population) 
TABLE 14.3.3.1 
Summary of All Suspected to Be Drug-Related Adverse Events by System Organ 
Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.3.2 
Summary of All Suspected to Be Drug-Related Adverse Events by System Organ 
Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.3.3 
Summary of All Injection Related Suspected to Be Drug-Related Adverse Events 
by System Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.3.4 
Summary of All Injection Suspected to Be Drug-Related Adverse Events by 
System Organ Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.3.5 
Summary of All Non-Injection Related Suspected to Be Drug-Related Adverse 
Events by System Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.3.6 
Summary of All Non-Injection Suspected to Be Drug-Related Adverse Events by 
System Organ Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.4.1 
Summary of All Adverse Events by System Organ Class, Preferred Term, and 
Severity (Overall Safety Population) 
TABLE 14.3.4.2 
Summary of All Adverse Events by System Organ Class, Preferred Term, and 
Severity (Full Exposure Safety Population) 
TABLE 14.3.4.3 
Summary of All Injection-Related Adverse Events by System Organ Class, 
Preferred Term, and Severity (Overall Safety Population) 
TABLE 14.3.4.4 
Summary of All Injection-Related Adverse Events by System Organ Class, 
Preferred Term, and Severity (Full Exposure Safety Population) 
TABLE 14.3.4.5 
Summary of All Non-Injection Related Adverse Events by System Organ Class, 
Preferred Term, and Severity (Overall Safety Population)  
TABLE 14.3.4.6 
Summary of All Non-Injection Related Adverse Events by System Organ Class, 
Preferred Term, and Severity (Full Exposure Safety Population) 
TABLE 14.3.5.1.1 
Summary of Most Common (at least 5%) Adverse Events by System Organ 
Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.5.1.2 
Summary (number of patients and number of events) of Most Common (at least 
5%) Non-Serious Adverse Events by System Organ Class and Preferred Term 
(Overall Safety Population) 
TABLE 14.3.5.1.3 
Summary (number of patients and number of events) of Serious Adverse Events 
by System Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.5.2 
Summary of Most Common (at least 5%) Adverse Events by System Organ 
Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.5.3 
Summary of Most Common (at least 5%) Injection-Related Adverse Events by 
System Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.5.4 
Summary of Most Common Injection-Related (at least 5%) Adverse Events by 
System Organ Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.5.5 
Summary of Most Common (at least 5%) Non-Injection Related Adverse Events 


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by System Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.5.6 
Summary of Most Common Non-Injection Related (at least 5%) Adverse Events 
by System Organ Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.6.1 
Summary of All Serious Adverse Events by System Organ Class and Preferred 
Term (Overall Safety Population) 
TABLE 14.3.6.2 
Summary of All Serious Adverse Events by System Organ Class and Preferred 
Term (Full Exposure Safety Population) 
TABLE 14.3.6.3 
Summary of All Injection-Related Serious Adverse Events by System Organ 
Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.6.4 
Summary of All Injection-Related Serious Adverse Events by System Organ 
Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.6.5 
Summary of All Non-Injection Related Serious Adverse Events by System 
Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.6.6 
Summary of All Non-Injection Related Serious Adverse Events by System 
Organ Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.7.1 
Summary of All Adverse Events That Lead to Treatment/Study Discontinuation 
by System Organ Class and Preferred Term (Overall Safety Population) 
TABLE 14.3.7.2 
Summary of All Adverse Events That Lead to Treatment/Study Discontinuation 
by System Organ Class and Preferred Term (Full Exposure Safety Population) 
TABLE 14.3.7.3 
Summary of All Injection Related Adverse Events That Lead to Treatment/Study 
Discontinuation by System Organ Class and Preferred Term (Overall Safety 
Population) 
TABLE 14.3.7.4 
Summary of All Injection-Related Adverse Events That Lead to Treatment/Study 
Discontinuation by System Organ Class and Preferred Term (Full Exposure 
Safety Population) 
TABLE 14.3.7.5 
Summary of All Non-Injection Related Adverse Events That Lead to 
Treatment/Study Discontinuation by System Organ Class and Preferred Term 
(Overall Safety Population) 
TABLE 14.3.7.6 
Summary of All Non-Injection Related Adverse Events That Lead to 
Treatment/Study Discontinuation by System Organ Class and Preferred Term 
(Full Exposure Safety Population) 
TABLE 14.3.8.1 
Summary of All Serious Adverse Events That Lead to Treatment/Study 
Discontinuation by System Organ Class and Preferred Term (Overall Safety 
Population) 
TABLE 14.3.8.2 
Summary of All Serious Adverse Events That Lead to Treatment/Study 
Discontinuation by System Organ Class and Preferred Term (Full Exposure 
Safety Population) 
TABLE 14.3.8.3 
Summary of All Injection Related Serious Adverse Events That Lead to 
Treatment/Study Discontinuation by System Organ Class and Preferred Term 
(Overall Safety Population) 
TABLE 14.3.8.4 
Summary of All Injection Related Serious Adverse Events That Lead to 
Treatment/Study Discontinuation by System Organ Class and Preferred Term 
(Full Exposure Safety Population) 
TABLE 14.3.8.5 
Summary of All Non-Injection Related Serious Adverse Events That Lead to 
Treatment/Study Discontinuation by System Organ Class and Preferred Term 
(Overall Safety Population) 
TABLE 14.3.8.6 
Summary of All Non-Injection Related Serious Adverse Events That Lead to 


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Treatment/Study Discontinuation by System Organ Class and Preferred Term 
(Full Exposure Safety Population) 
TABLE 14.3.9.1 
Summary of All Deaths and Hospitalizations (Overall Safety Population) 
TABLE 14.3.9.2 
Summary of All Deaths and Hospitalizations (Full Exposure Safety Population) 
TABLE 14.3.9.3 
Summary of All Injection-Related Deaths and Hospitalizations (Overall Safety 
Population) 
TABLE 14.3.9.4 
Summary of All Injection-Related Deaths and Hospitalizations (Full Exposure 
Safety Population) 
TABLE 14.3.9.5 
Summary of All Non-Injection Related Deaths and Hospitalizations (Overall 
Safety Population) 
TABLE 14.3.9.6 
Summary of All Non-Injection Related Deaths and Hospitalizations (Full 
Exposure Safety Population) 
TABLE 14.3.10.1 
Summary of Columbia-Suicide Severity Ratings over Time (Overall Safety 
Population) 
TABLE 14.3.10.2 
Summary of Columbia-Suicide Severity Ratings over Time (Full Exposure 
Safety Population) 
TABLE 14.3.11.1 
Summary of Clinical Hematology Data over Time (Overall Safety Population) 
TABLE 14.3.11.2 
Summary of Clinical Hematology Data over Time (Full Exposure Safety 
Population) 
TABLE 14.3.12.1 
Shift from Baseline in Laboratory Tests: Hematology (Overall Safety 
Population) 
TABLE 14.3.12.2 
Shift from Baseline in Laboratory Tests: Hematology (Full Exposure Safety 
Population) 
TABLE 14.3.13.1 
Summary of Clinical Chemistry Data (Overall Safety Population) 
TABLE 14.3.13.2 
Summary of Clinical Chemistry Data (Full Exposure Safety Population) 
TABLE 14.3.14.1 
Shift from Baseline in Laboratory Tests: Chemistry (Overall Safety Population) 
TABLE 14.3.14.2 
Shift from Baseline in Laboratory Tests: Chemistry (Full Exposure Safety 
Population) 
TABLE 14.3.15.1 
Summary of Clinical Coagulation Profile Data (Overall Safety Population) 
TABLE 14.3.15.2 
Summary of Clinical Coagulation Profile Data (Full Exposure Safety Population) 
TABLE 14.3.16.1 
Shift from Baseline in Laboratory Tests: Coagulation Profile (Overall Safety 
Population) 
TABLE 14.3.16.2 
Shift from Baseline in Laboratory Tests: Coagulation Profile (Full Exposure 
Safety Population) 
TABLE 14.3.17.1 
Summary of Vital Signs over Time (Overall Safety Population) 
TABLE 14.3.17.2 
Summary of Vital Signs over Time (Full Exposure Safety Population) 
TABLE 14.3.18.1 
Summary of 12-Lead ECG Results (Overall Safety Population) 
TABLE 14.3.18.2 
Summary of 12-Lead ECG Results (Full Exposure Safety Population) 
TABLE 14.3.19.1	  
Summary of 12-Lead ECG Individual Parameters (Overall Safety Population) 
TABLE 14.3.19.2	  
Summary of 12-Lead ECG Individual Parameters (Full Exposure Safety 
Population) 
 
List of Listings 
Number 
Title 
LISTING 16.2.1.1 
Patient Meeting Inclusion Criteria 
LISTING 16.2.1.2 
Patients Meeting Exclusion Criteria 
LISTING 16.2.2	  
Protocol Deviations 


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LISTING 16.2.3	  
Patient Disposition 
LISTING 16.2.4.1	  
Demographics 
LISTING 16.2.4.2	  
Psychosocial History  
LISTING 16.2.4.3	  
Medical History 
LISTING 16.2.4.4 
Substance Abuse History and Treatment 
LISTING 16.2.5.1	  
CAM2038 Injection 
LISTING 16.2.5.2	  
Injection Site Examination/ Treatment Compliance 
LISTING 16.2.6.1 
COWS, SOWS 
LISTING 16.2.6.2 
Need to Use and Desire to Use VAS  
LISTING 16.2.6.3 
Urine Toxicology Results for Illicit Opioids 
LISTING 16.2.6.4 
Self-Reported Illicit Opioid Use 
LISTING 16.2.6.5 
Urine Toxicology Results for Other Drugs of Abuse 
LISTING 16.2.6.6 
Work Productivity and Activity Impairment Questionnaire General Health 
(WPAI-GH) 
LISTING 16.2.6.7 
EQ-5D-5L Health Questionnaire 
LISTING 16.2.6.8 
Patient Satisfaction Scale 
LISTING 16.2.6.9 
Psychosocial Counseling 
LISTING 16.2.7.1 
Adverse Events 
LISTING 16.2.7.2 
Serious Adverse Events 
LISTING 16.2.7.3 
Adverse Events That Lead to Discontinuation from Treatment/Study  
LISTING 16.2.7.4 
Adverse Events That Have Death as the Outcome 
LISTING 16.2.7.5 
Death Reports 
LISTING 16.2.7.6 
Prior and Concomitant Medications/Procedures 
LISTING 16.2.8.1 
Lab Test Samples 
LISTING 16.2.8.2 
Clinical Hematology 
LISTING 16.2.8.3 
Clinical Chemistry 
LISTING 16.2.8.4 
Clinical Coagulation Profile 
LISTING 16.2.8.5 
Urinalysis 
LISTING 16.2.8.6 
Serology 
LISTING 16.2.8.7 
Pregnancy Test  
LISTING 16.2.8.8 
Pregnancies 
LISTING 16.2.9 
C-SSRS 
LISTING 16.2.10 
Physical Examination 
LISTING 16.2.11 
Vital Signs 
LISTING 16.2.12 
12-Lead ECG 
LISTING 16.2.13 
Patient Visits 
	  
List of Figures 
FIGURE 14.2.1 
Kaplan-Meier Plot of Time to Treatment Discontinuation (retention in treatment) 
(Efficacy Population) 
FIGURE 14.2.2 
Kaplan-Meier Plot of Time to Study Discontinuation (retention in study) 
(Efficacy Population) 
FIGURE 14.2.3 
Urine Toxicology Results for Illicit Opioid Use Supported by Self-Reported 
Illicit Opioid Use by Time (Efficacy Population) 
FIGURE 14.2.4 
Urine Toxicology Results for Illicit Opioid Use Without Self-Reported Illicit 
Opioid Use by Time (Efficacy Population) 


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15.2   APPENDIX	  B	  -­‐‑	  IMPUTATION	  ALGORITHM	  FOR	  PARTIAL	  AND	  MISSING	  
DATES	  	  
This section describes missing date imputation methods. 
 
For Adverse Events 
 
If onset date is completely missing, onset date is set to the date of first study dose date. 
If (year is present and month and day are missing) or (year and day are present and month is missing): 
•  
If year = year of first dosing, then set month and day to month and day of first dosing 
•  
If year < year of first dosing, then set month and day to December 31. 
•  
If year > year of first dosing, then set month and day to January 1. 
If month and year are present and day is missing: 
•  
If year=year of first dosing and   
•  
If month = month of first dosing then set day to day of first dose 
•  
If month < month of first dose then set day to last day of month 
•  
If month > month of first dose then set day to first day of month 
•  
If year < year of first dosing then set day to last day of month 
•  
If year > year of dosing then set day to first day of month 
 
For all other cases, set onset date to date of first dosing. 
 
For Concomitant Medications 
 
Start Date:  If start date is completely missing and end date is not prior to first dosing, then the medication 
will be classified as concomitant. If start date is completely missing and end date is prior to first dosing, 
then the medication will be classified as prior. 
 
If (year is present and month and day are missing) or (year and day are present and month is missing) then 
set month and day to January 1.  If year and month are present and day is missing then set day to first day 
of month. 
 
End Date:  If end date is completely missing then the medication will be classified as concomitant. 
If (year is present and month and day are missing) or (year and day are present and month is missing) then 
set month and day to December 31.  If year and month are present and day is missing then set day to last 
day of the month. 
 
Note: that if both start and end dates are missing then the medication will be classified as concomitant.