An Open-Label, Depot Buprenorphine (RBP-6000) Treatment Extension Study in Subjects With Opioid Use Disorder
Phase: PHASE3
Conditions: Opioid Use Disorder, Opioid-related Disorders
Sponsor: Indivior Inc.

NCT02896296 
 
Study Number:  INDV-6000-301 
 
Title:  An Open-Label, Depot Buprenorphine (RBP-6000) Treatment Extension 
Study in Subjects With Opioid Use Disorder 
 
Protocol Date:  30 September 2016 

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Clinical Study Protocol: INDV-6000-301
Study Title:
An Open-Label, Depot Buprenorphine (RBP-6000) Treatment 
Extension Study in Subjects with Opioid Use Disorder
Study Number:
INDV-6000-301
Study Phase:
3
Product Name:
RBP-6000
IND Number:
107,607
Indication:
Treatment of Opioid Use Disorder
Investigators:
Multicenter
Sponsor:
Indivior Inc.
10710 Midlothian Turnpike, Suite 430
Richmond, VA 23235
Sponsor Contact:
Head Late Stage Development, Global Clinical Development
Medical Monitor:
Scientific Research Fellow, Global Clinical Development
Date
Original Protocol:
24 June 2016
Amendment 1
30 September 2016
Confidentiality Statement
The information contained in this document is privileged and confidential. Do not copy, 
circulate, or otherwise distribute without written authorization from 
Indivior Inc.

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Clinical Study Protocol: INDV-6000-301
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SYNOPSIS
Sponsor: 
Indivior Inc.
Name of Finished Product:
RBP-6000, 18% buprenorphine sterile solution for subcutaneous (SC) injection
Name of Active Ingredient:
Buprenorphine
Name of Inactive Ingredient: 
ATRIGEL® Delivery System
Study Title:
An Open-Label, Depot Buprenorphine (RBP-6000) Treatment Extension Study in Subjects with 
Opioid Use Disorder
Study Number:
INDV-6000-301
Study Phase: Phase 3
Study Objective:
To provide ongoing treatment with RBP-6000 and safety monitoring for subjects who complete 
the RB-US-13-0003 study and for whom a new treatment venue has not been identified or 
arranged.
Study Design:
This is a multicenter, open-label, RBP-6000 treatment extension study in which approximately 
300 subjects diagnosed with Opioid Use Disorder (OUD) will be enrolled. Enrollment is defined 
as the first dose of RBP-6000 administered for this study. Only subjects who have completed the 
End of Study (EOS) procedures for Study RB-US-13-0003, have signed the INDV-6000-301 
informed consent form (ICF), and meet all the enrollment criteria may be considered for 
inclusion in this study.
The institutional review board (IRB) approved ICF may be shared with the potential subject up 
to 2 months before EOS Visit for Study RB-US-13-0003 in order to discuss this study as a 
possible treatment option. However, the ICF for Study INDV-6000-301 must not be signed until 
all assessments for the RB-US-13-0003 EOS Visit are complete.
The RB-US-13-0003 EOS assessments completed at the EOS Visit will serve as part of the 
screening assessments for this study. In addition, medical history will be collected, height 
measured, and subjects will be requested to complete a Columbia Suicide Severity Rating Scale 
(C-SSRS) baseline survey. The same-day Study RB-US-13-0003 EOS Visit / INDV-6000-301 
Screening Visit will also be considered Day 1 of this study.
On Day 1, eligible subjects will receive a subcutaneous (SC) injection of RBP-6000. For each 
injection, subjects may receive either a dose of 100 mg RBP-6000 or 300 mg RBP-6000, based 
on the medical judgment of the Investigator. Following RBP-6000 injection, vital signs and the 
injection site will be assessed. The injection site will be assessed by the site for pain, tenderness, 
warmth, itching, erythema, inflammation or swelling, and bruising using a 5-point severity scale 

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(the Injection Site Grading Scale). In addition, the subject will assess their own injection site 
pain using a visual analog scale (VAS) (referred to as the Injection Site Pain VAS).  Before 
departing the site, the subject will also be assessed for adverse events (AEs) and use of 
concomitant medications. 
Subjects will not be permitted to receive supplemental buprenorphine during the RBP-6000 
treatment period (Day 1 to EOS/ET Visit).  Subjects who require supplemental buprenorphine 
pharmacotherapy during the RBP-6000 treatment period will be withdrawn from the study and 
referred for appropriate treatment.
Subjects will return to the site for monthly injection visits every 28 days (-2 / +7 days) for a total 
of up to 6 injections. Subjects are not required to complete all 6 injections and may choose to 
“early terminate” (ET) the study at any time.
At each subsequent visit (Injection Visits 2 through 6) the following procedures and assessments 
will be performed:   urine pregnancy test for all female subjects who are of childbearing potential 
before each injection; evaluation of previous injection site for potential reaction and evidence of 
attempts to remove the depot; collection of vital signs pre- and post-injection; RBP-6000 
injection, urine drug screen (UDS); C-SSRS since last visit, counseling (manual-guided 
behavioral therapy); local injection site grading; subject self-assessment of injection site pain 
(Injection Site Pain VAS); use of concomitant medications; and assessment for AEs. Laboratory 
tests (hematology, chemistry and urinalysis) may be requested by the Investigator on an ad-hoc 
basis as necessary to further examine any AEs. 
Alternative treatment options should be assessed at least two months before EOS at each visit, 
however it is recommended where possible to assess at every visit. 
At the EOS/ET Visit, the following procedures and assessments will be performed: urine 
pregnancy test for all female subjects who are of childbearing potential; evaluation of previous 
injection site for potential reaction and evidence of attempts to remove the depot; vital sign 
measurements; UDS; C-SSRS since last visit, counseling (manual-guided behavioral therapy); 
use of concomitant medications; assessment for AEs; brief physical exam; height and body 
weight measurement (to determine a subject’s body mass index [BMI]); hip and waist 
circumference measurement (to determine a subject’s hip-to-waist ratio); and laboratory tests 
(hematology, chemistry, urinalysis). 
Approximately 4 weeks after EOS/ET Visit, all subjects should be contacted by telephone for a 
safety follow-up assessment of AEs and use of any concomitant medications. 
Study Population:
All subjects who completed the RB-US-13-0003 study may be eligible to enroll into this study. 
Approximately 300 subjects will be enrolled. 
Test Product, Dose, and Mode of Administration:
300 mg buprenorphine in RBP-6000, subcutaneous injection
100 mg buprenorphine in RBP-6000, subcutaneous injection
Duration of Study Treatment:
This will be a multiple-dose study, with the first investigational product administration 
(RBP-6000) occurring on Study Day 1. The expected duration of participation for each subject is 
up to approximately 29 weeks, consisting of a 25-week, open-label treatment period and a safety 

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follow-up phone call at 4 weeks after the EOS/ET Visit.
Safety Assessments:
Safety will be assessed throughout the entire study on the basis of the following: AEs, serious 
adverse events (SAE)s, discontinuations from study due to AEs; local injection site tolerability 
(based on injection site grading); injection site pain using a subject-reported VAS; suicidality 
using the C-SSRS, use of concomitant medications; clinically significant changes in clinical 
laboratory results; vital sign measurements; physical examination findings; and measurements of 
body weight, height, waist and hip circumference (for calculation of BMI and abdominal fat 
measurement [waist-to-hip ratio]).
Statistical Methods:
A Statistical Analysis Plan (SAP) will be finalized before database lock occurs.  The SAP will 
provide further details regarding the definition of analysis endpoints, data handling rules, and the 
statistical methodology to be used to address all study objectives.  The SAP will also include 
formats for the summary and analysis tables, listings, and graphical displays.
Determination of Sample Size:
Approximately 300 subjects who completed Study RB-US-13-0003 will be enrolled into this 
study.
Safety Analyses:
Safety variables will include AEs, local injection site tolerability (e.g., injection site grading); 
injection site pain using a subject-reported VAS; suicidality using the C-SSRS, concomitant 
medications; changes in clinical laboratory results (hematology, chemistry and urinalysis); vital 
sign measurements; physical examination results; body weight, height, BMI, and abdominal fat 
measurement (waist-to-hip ratio). Safety variables will be described using descriptive statistics 
for continuous endpoints (e.g., mean, median, standard deviation (SD), minimum and maximum) 
and frequency counts with percentages for discrete endpoints.
Baseline is defined as the value collected at Screening.  No imputation of missing values will be 
performed.
Date of Original Protocol: 24 June 2016
Date of Protocol Amendment 1:  30 September 2016

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TABLE OF CONTENTS
SYNOPSIS.................................................................................................................................2
LIST OF IN-TEXT TABLES ....................................................................................................8
LIST OF IN-TEXT FIGURES...................................................................................................8
LIST OF APPENDICES............................................................................................................8
LIST OF ABBREVIATIONS....................................................................................................9
1
INTRODUCTION ...........................................................................................................11
1.1
Background Information........................................................................................11
1.2
Rationale for Dose Selection .................................................................................14
1.3
Known and Potential Risks and Benefits...............................................................14
1.4
Good Clinical Practice...........................................................................................14
2
STUDY OBJECTIVE......................................................................................................16
3
INVESTIGATIONAL PLAN..........................................................................................17
3.1
Overall Study Design and Plan..............................................................................17
3.2
Rationale for Study Design....................................................................................20
3.3
Study Duration and Dates......................................................................................20
4
STUDY POPULATION SELECTION ...........................................................................21
4.1
Study Population....................................................................................................21
4.2
Inclusion Criteria ...................................................................................................21
4.3
Exclusion Criteria ..................................................................................................21
5
STUDY TREATMENTS.................................................................................................23
5.1
Description of Treatment.......................................................................................23
5.2
Treatments Administered.......................................................................................23
5.3
Selection and Timing of Dose for Each Subject....................................................23
5.4
Method of Assigning Subjects to Treatment Groups.............................................23
5.5
Blinding..................................................................................................................24
5.6
Restrictions ............................................................................................................24
5.7
Dosing Compliance................................................................................................24
5.8
Packaging and Labeling.........................................................................................24
5.9
Product Quality Complaints...................................................................................24
5.10
Storage and Accountability....................................................................................24
5.11
IMP Retention at Study Site ..................................................................................25
6
STUDY PROCEDURES .................................................................................................26
6.1
Medical History .....................................................................................................26
6.2
Physical Examination.............................................................................................26
6.3
Body Mass Index and Hip-to-Waist Ratio.............................................................26
6.4
Vital Signs..............................................................................................................27

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6.5
Clinical Laboratory Tests.......................................................................................27
6.5.1
Laboratory Parameters.................................................................................27
6.5.2
Sample Collection, Storage, and Shipping ..................................................28
6.5.3
Reference Ranges.........................................................................................29
6.5.4
Laboratory Results Review..........................................................................29
6.6
Suicidality Assessments.........................................................................................29
6.7
Local Injection Site Tolerability............................................................................29
6.7.1
Injection Site Evaluation..............................................................................29
6.7.2
Injection Site Grading..................................................................................30
6.7.3
Injection Site Pain Visual Analog Scale (VAS) ..........................................30
6.8
Pharmacokinetic Assessments ...............................................................................30
6.9
Adverse Events Assessments.................................................................................30
6.9.1
Adverse Event Definition ............................................................................30
6.9.2
Treatment-Emergent Adverse Event Definition ..........................................31
6.9.3
Performing Adverse Events Assessments....................................................31
6.9.4
Timing..........................................................................................................31
6.9.5
Severity ........................................................................................................32
6.9.6
Relationship .................................................................................................32
6.9.7
Expectedness................................................................................................32
6.9.8
Clinical Significance....................................................................................33
6.9.9
Clinical Laboratory Adverse Events............................................................33
6.9.10
Serious Adverse Events ...............................................................................33
6.9.11
Serious Adverse Event Definition ...............................................................33
6.9.11.1
Suspected Unexpected Serious Adverse Event Definition................33
6.9.11.2
Reporting Serious Adverse Events ....................................................34
6.9.12
Pregnancy.....................................................................................................34
6.10
Concomitant Medication Assessments ..................................................................35
6.10.1
Prohibited Concomitant Medications ..........................................................35
6.11
Counseling/Behavioral Therapy ............................................................................36
6.12
Removal of Subjects from the Study .....................................................................36
6.12.1
Early Removal of RBP-6000 .......................................................................36
6.12.2
Stopping Rules.............................................................................................37
6.12.3
Lost to Follow-up.........................................................................................37
6.12.4
Screen Failures.............................................................................................37
6.13
Other Study Procedures .........................................................................................37
6.13.1
Unscheduled Visits ......................................................................................37
6.14
Appropriateness of Measurements.........................................................................38
7
STUDY ACTIVITIES .....................................................................................................39
8
QUALITY CONTROL AND ASSURANCE .................................................................40

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8.1
Quality Control ......................................................................................................40
8.2
Quality Assurance..................................................................................................40
9
PLANNED STATISTICAL METHODS ........................................................................41
9.1
General Considerations..........................................................................................41
9.2
Determination of Sample Size ...............................................................................41
9.3
Analysis Populations..............................................................................................41
9.4
Demographics and Baseline Characteristics..........................................................41
9.5
Primary Analysis....................................................................................................41
9.5.1.1
Adverse Events ..................................................................................42
9.5.1.2
Laboratory Data .................................................................................42
9.5.1.3
Vital Signs..........................................................................................42
9.5.1.4
Other Variables Related to Safety......................................................42
9.6
Handling of Missing Data......................................................................................43
9.7
Subjects Who Withdraw from the Study ...............................................................43
9.8
Interim Analyses ....................................................................................................43
10
ADMINISTRATIVE CONSIDERATIONS....................................................................44
10.1
Investigators and Study Administrative Structure.................................................44
10.1.1
Sponsor ........................................................................................................44
10.1.2
Investigational Site(s) ..................................................................................44
10.1.3
Laboratories .................................................................................................44
10.2
Institutional Review Board Approval....................................................................44
10.3
Ethical Conduct of the Study.................................................................................44
10.4
Subject Informed Consent......................................................................................45
10.5
Subject Confidentiality ..........................................................................................45
10.6
Study Monitoring...................................................................................................45
10.6.1
Study and Site Closure.................................................................................46
10.7
Case Report Forms and Study Records .................................................................46
10.8
Data Monitoring Committee..................................................................................47
10.9
Protocol Deviations................................................................................................47
10.10 Access to Source Documentation ..........................................................................47
10.11 Data Generation and Analysis ...............................................................................48
10.11.1
Data Collection and Data Management.......................................................48
10.11.2
Database Quality Assurance ........................................................................48
10.12 Retention of Data...................................................................................................48
10.13 Financial Disclosure...............................................................................................48
10.14 Publication and Disclosure Policy .........................................................................49
11
REFERENCE LIST .........................................................................................................50

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LIST OF IN-TEXT TABLES
Table 1
Summary of Completed RBP-6000 Clinical Studies...................................12
Table 2
List of Laboratory Tests...............................................................................28
LIST OF IN-TEXT FIGURES
Figure 1
Study Overview ...........................................................................................19
Figure 2
Injection Locations.......................................................................................54
LIST OF APPENDICES
Appendix 1
Schedule of Events.............................................................................51
Appendix 2
IMP Preparation, Administration, and Depot Removal Instructions.53
Appendix 3
Prohibited Cytochrome P450 Inhibitors and Inducers.......................56
Appendix 4
Columbia Suicide Severity Rating Scale (C-SSRS) --
Baseline/Screening Version.........................................................................................58
Appendix 5
Columbia Suicide Severity Rating Scale (C-SSRS) --  Since Last 
Visit Version
60
Appendix 6
Injection Site Grading Scale ..............................................................62
Appendix 7
Injection Site Pain Visual Analog Scale............................................63
Appendix 8
Elevated Liver Function Tests ...........................................................64
Appendix 9
Sponsor Signatures.............................................................................66
Appendix 10
Investigator’s Signature .....................................................................67

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LIST OF ABBREVIATIONS
AE
Adverse event
ALP
Alkaline phosphatase 
ALT
Alanine aminotransferase
AST
Aspartate transaminase
BMI
Body mass index
BUN
Blood urea nitrogen
CRA
Clinical Research Associate
C-SSRS
Columbia Suicide Severity Rating Scale
DSM-5
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition
eCRF
Electronic case report form
ECG
Electrocardiogram
EOS
End of study
ET
Early termination
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HDL
High-density lipoprotein
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation 
IM
Intramuscular
IMP
Investigational medicinal product
IRB
Institutional review board
IV
Intravenous
IWRS
Interactive web response system
LDL
Low-density lipoprotein 
NMP
N-methyl-2-pyrrolidone
OTC
Over-the-counter
OUD
Opioid Use Disorder

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PK
Pharmacokinetic
PLGH
Poly (DL-lactide-co-glycolide) 
QA
Quality Assurance
SAE
Serious adverse event
SAP
Statistical analysis plan
SC
Subcutaneous
SD
Standard deviation
SL 
Sublingual
SOE
Schedule of events
SOP
Standard operating procedure
SUSAR
Suspected Unexpected Serious Adverse Reaction
TEAE
Treatment-emergent adverse event
UDS
Urine Drug Screen
US/USA
United States/United States of America
VAS
Visual analog scale
WHO
World Health Organization 

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1
INTRODUCTION
Opioid use disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders, 
Fifth Edition (DSM-5; American Psychiatric Association 2013), is a neurobehavioral syndrome 
characterized by the repeated, compulsive seeking or use of an opioid despite adverse social, 
psychological, and/or physical consequences.  Opioid use disorder (OUD) is a medical illness 
with high costs to individuals, families, and society.  Direct and indirect costs attributable to 
illicit drug use are estimated in 3 principal areas: crime, productivity, and health (US Department 
of Justice, Economic Impact of Illicit Drug Use on American Society, 2011). These high costs 
have prompted researchers to seek new medications and treatment strategies for opioid 
dependence aiming to reduce the use of prescription or illicit opioids.  
Buprenorphine, a mu-opioid receptor partial agonist and kappa-opioid receptor antagonist, is one 
such medication that has had a significant role in expanding access to effective opioid 
dependence treatment. Buprenorphine has been approved for use in the treatment of opioid 
dependence in a number of countries worldwide. Buprenorphine has been reported to have a 
lower physical dependence liability than pure agonist analgesics such as morphine, and at a 
sufficient dose, it can suppress opioid withdrawal signs and symptoms for at least 24 hours.  
Limited euphoric and respiratory depressant effects have led to its therapeutic use as a 
pharmacotherapy for opioid use disorder.
The sponsor is currently developing a buprenorphine depot (RBP-6000), which is a 
subcutaneously injected for the treatment of OUD.  It contains buprenorphine in the ATRIGEL 
Delivery System and provides sustained plasma levels of buprenorphine over a minimum of 28 
days (RBP-6000 IB).  
The ATRIGEL Delivery System is a sterile, polymeric solution of a biodegradable 
poly DL-lactide-co-glycolide (PLGH) copolymer, dissolved in the water-miscible, biocompatible 
solvent N-methyl-2-pyrrolidone (NMP).  The ATRIGEL Delivery System is well characterized.  
It is currently used in 7 approved products worldwide, including 4 ELIGARD® products 
(subcutaneous [SC] depot formulations of leuprolide acetate), ATRIDOX® (doxycycline hyclate 
applied to the periodontal pocket), the ATRISORB® Bioabsorbable Guided Tissue Regeneration 
Barrier for periodontal application, and the ATRISORB-D Barrier (ATRISORB with 
doxycycline) for periodontal guided tissue regeneration.
1.1
Background Information
To date, there have been 4 clinical studies completed using RBP-6000 (Table 1).

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Table 1
Summary of Completed RBP-6000 Clinical Studies
Study
Study Title
IMP
(Dose)
Most Common
AE(s) Possibly Related to 
Study Drug
Other Safety
RB-US-10-0011
A Single-Dose, Open-Label Study 
of Depot Buprenorphine (RBP-
6000) in Opioid Dependent 
Individuals
RBP-6000
(20 mg)
Drug withdrawal syndrome
Injection site pain
Rebound hypertension
Constipation
Headache
Injection site warmth
Respiratory rate increased
No clinically significant trends in vital signs, 
ECGs, clinical laboratory tests, or physical 
examinations.
No deaths or SAEs related to treatment and 
no subjects discontinued due to an AE.
RB-US-11-0020
A Multicenter, Open-Label, Single 
Ascending-Dose Study to 
Evaluate the Safety, Tolerability, 
and Pharmacokinetics of Depot 
Buprenorphine (RBP-6000) in 
Opioid-Dependent Subjects
RBP-6000
(50 mg, 
100 mg, and 
200 mg)
Drug withdrawal syndrome
Constipation
Diarrhea
Nausea
Injection site pain
No clinically significant trends in vital signs, 
ECGs, clinical laboratory tests, or physical 
examinations.
No deaths or SAEs related to treatment and 
no subjects discontinued due to an AE.
RB-US-12-0005
An Open-Label, Multicenter, 
Multiple Dose Study of the Safety, 
Tolerability, Pharmacokinetics, 
Efficacy Markers, and Opioid 
Receptor Availability of 
Subcutaneous Injections of Depot 
Buprenorphine (RBP-6000) in 
Treatment Seeking Opioid 
Dependent Subjects
RBP-6000
(50 mg, 
100 mg, 
200 mg, and 
300 mg)
Drug withdrawal syndrome
Vomiting
Constipation
Musculoskeletal pain
Anxiety
Upper Respiratory Tract
Infection
Liver function test abnormal
No clinically significant trends in 
hematology, serum chemistry, urinalysis, 
vital signs, or ECGs.
There were 9 SAEs during the study; 3 
subjects withdrawn due to SAEs; 8 subjects 
withdrawn from the study due to a TEAE. 
None of the above events were considered 
related to study medication.
RB-US-13-0002
A Multiple-Dose Study of 
Blockade of Subjective Opioid 
Effects, Pharmacokinetics, and 
Safety of Subcutaneous Injections 
of Depot Buprenorphine (RBP-
6000) in Subjects with Opioid Use 
Disorder
RBP-6000
(300 mg)
Drug withdrawal syndrome
Headache
Anxiety
Constipation
Liver function test abnormal
Injection site reaction
No clinically significant trends in 
hematology, serum chemistry, urinalysis, 
vital signs, and ECGs.
No deaths, no SAEs, and no withdrawals 
from the study due to a TEAE.
AE = Adverse Event; ECG = Electrocardiogram; IMP = Investigational medicinal product; SAE = Serious adverse event; TEAE = Treatment-emergent 
adverse event.

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In summary, doses of 50, 100, 200 and 300 mg RBP-6000 have been administered to male and 
female subjects and have been safe and well tolerated.  (RBP-6000 IB).  
A population pharmacokinetic (PK) model was developed to characterize the disposition of 
buprenorphine and norbuprenorphine following SC injection of RBP-6000 (Nasser 2014).  The 
population PK model accurately predicted the PK data after repeated doses of RBP-6000 in the 
multiple ascending dose study (RB-US-12-0005) and in the opioid blockade study (RB-US-13-
0002). Another population PK/PD model was developed to characterize the link between 
buprenorphine plasma concentration and mu opioid receptor occupancy (Nasser 2014).  The 
model simulations indicated that the desired 70% mu opioid receptor occupancy may be 
achieved after multiple doses of 200 mg of RBP-6000.  The 300 mg dose was considered to be a 
full opioid blockade dose.
There are currently 2 studies in the process of being completed and 1 study is ongoing:

RB-US-13-0006 – A Single-Center, Randomized, Open-Label, Single-Dose Study to 
Evaluate the Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine (RBP-
6000) Using Poly (DL-lactide-co-glycolide) Polymer of Two Different Molecular 
Weights (Low and High Molecular Weights as Test Treatments) in Comparison to 
Intermediate Molecular Weight (Reference Treatment) in Treatment-Seeking Subjects 
with Opioid Use Disorder.  [Study Status: Study has concluded/analysis in progress]
o
An investigational Phase I PK study evaluating the PK, safety, and tolerability of 
300 mg RBP-6000 using different molecular weights of the PLGH within the 
ATRIGEL delivery system, in Treatment-Seeking Subjects with OUD. 

RB-US-13-0001 - A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study 
To Assess the Efficacy, Safety, and Tolerability of Multiple Subcutaneous Injections of 
Depot Buprenorphine (RBP-6000 [100 mg and 300 mg]) Over 24 Weeks in Treatment-
Seeking Subjects with Opioid Use Disorder.  [Study Status: Study has concluded/analysis 
in progress]
o
A Phase III double-blind, placebo controlled efficacy study. The study is 
assessing the Efficacy, Safety, and Tolerability of 6 Subcutaneous Injections of 
RBP-6000 [100 mg and 300 mg] (or placebo) in approximately 500 treatment-
seeking subjects with OUD. Subjects who successfully completed this study were 
permitted to enroll in study RB-US-13-0003, if eligible. 

RB-US-13-0003 - An Open-Label, Long-Term Safety and Tolerability Study of Depot 
Buprenorphine (RBP-6000) in Treatment-Seeking Subjects With Opioid Use Disorder. 
[Study Status: Ongoing/analysis is pending]
o
A Phase III, open-label, long-term safety and tolerability Study of RBP-6000 in 
approximately 600 treatment-seeking subjects with OUD.  Subjects in this study 
will be dosed with a maximum of 12 injections of RBP-6000 (if enrolled directly 

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onto this study), and a maximum of 6 injections if enrolled from study RB-US-13-
0001. 
1.2
Rationale for Dose Selection
The doses proposed in this study are 100 mg RBP-6000 and 300 mg RBP-6000, which are the 
doses subjects are currently receiving in the RB-US-13-0003 study. These doses were chosen in 
the RB-US-13-0001 and RB-US-13-0003 studies as modeling and simulation (Nasser 2014) 
demonstrated that the 300 mg SC dose is an appropriate dose to assess for efficacy. The 100 mg 
RBP-6000 dose is provided because it is recognized that some individuals may need or desire 
lower dosages. 
Doses of RBP-6000 may be adjusted up or down (to either 100 mg or 300 mg) throughout the 
course of the study based on the medical judgment of the Investigator. 
1.3
Known and Potential Risks and Benefits
The AE profile of buprenorphine is well-characterized; commonly reported effects include 
constipation, nausea, vomiting, and headache.  Buprenorphine is approved for use by various 
routes of administration (e.g., sublingual [SL], intramuscular [IM], intravenous [IV], 
transdermal, and rectal).
Studies of buprenorphine receptor binding in human subjects have consistently and reproducibly 
established that buprenorphine is a highly lipophilic, mu-opioid receptor partial agonist with 
slow receptor association and dissociation kinetics.  Buprenorphine has an improved safety 
profile relative to mu-opioid receptor full agonists due to its partial agonist properties.  These 
attributes of buprenorphine allow it to perform well as substitution therapy for opioid-dependent 
individuals over short-term and long-term durations.  The experiments used to establish the 
binding profile of buprenorphine were consistent across differing parenteral routes of 
administration (IV, IM, and SL); therefore, RBP-6000 is expected to perform similarly when 
administered as a SC depot in the ATRIGEL Delivery System.
The purpose of this study (INDV-6000-301) is to continue to provide up to an additional 6 
injections of RBP-6000 for those subjects who have completed study RB-US-13-0003 and 
where a new treatment venue has not yet been identified, or arranged while ensuring their use of 
the product is monitored for safety. 
A sustained-release formulation of buprenorphine using the ATRIGEL Delivery System offers a 
number of potential benefits relative to shorter-acting formulations, including improved subject 
compliance, reduced diversion and misuse, as well as a reduced risk to subjects, their families, 
and the community.
1.4
Good Clinical Practice 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and documentation 
of this study, are designed to ensure that the Sponsor, designees and Investigator abide by Good 
Clinical Practice (GCP) as described in 21CFR parts 50, 54, 56, and 312 as well as in the 

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International Council for Harmonisation (ICH) Guidelines Topic E6 (R1): Guideline for Good 
Clinical Practice”. The study will also be carried out in accordance with local legal and 
regulatory requirements.

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2
STUDY OBJECTIVE
To provide ongoing treatment with RBP-6000 and safety monitoring for subjects who complete 
the RB-US-13-0003 study and for whom a new treatment venue has not been identified or 
arranged.

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3
INVESTIGATIONAL PLAN
3.1
Overall Study Design and Plan
This is a multicenter, open-label, RBP-6000 treatment extension study in which approximately 
300 subjects diagnosed with Opioid Use Disorder (OUD) will be enrolled. Enrollment is defined 
as the first dose of RBP-6000 administered for this study. Only subjects who have completed the 
End of Study (EOS) procedures for Study RB-US-13-0003, have signed the INDV-6000-301 
informed consent form (ICF), and meet all the enrollment criteria may be considered for 
inclusion in this study.  
The IRB approved ICF may be shared with the potential subject up to 2 months before EOS Visit 
for Study RB-US-13-0003 in order to discuss this study as a possible treatment option. However, 
the ICF for Study INDV-6000-301 must not be signed until all assessments for the RB-US-13-
0003 EOS Visit are complete.
The RB-US-13-0003 EOS assessments completed at the EOS Visit will serve as part of the 
screening assessments for this study. In addition, medical history will be collected, height 
measured, and the subjects will be requested to complete a Columbia Suicide Severity Rating 
Scale (C-SSRS) baseline/screening survey. The same-day Study RB-US-13-0003 EOS Visit / 
INDV-6000-301 Screening Visit will also be considered Day 1 of this study.
On Day 1, eligible subjects will receive a subcutaneous (SC) injection of RBP-6000. For each 
injection, subjects may receive either a dose of 100 mg RBP-6000 or 300 mg RBP-6000, based 
on the medical judgment of the Investigator. Following RBP-6000 injection, vital signs and the 
injection site will be assessed. The injection site will be assessed for pain, tenderness, warmth, 
itching, erythema, inflammation or swelling, and bruising using a 5-point severity scale 
(Injection Site Grading Scale). In addition, the subject will assess their own injection site pain 
using a visual analog scale (VAS) (referred to as the Injection Site Pain VAS). Before departing 
the site, the subject will also be assessed for adverse events (AEs) and use of concomitant 
medications.
Subjects will not be permitted to receive supplemental buprenorphine during the RBP-6000 
treatment period (Day 1 to EOS/ET Visit).  Subjects who require supplemental buprenorphine 
pharmacotherapy during the RBP-6000 treatment period will be withdrawn from the study and 
referred for appropriate treatment.  [Note: If subjects complete their EOS/ET Visit and a new 
treatment venue for them has not been identified, the Investigator may provide the subject further 
buprenorphine treatment or another appropriate treatment according to their own medical 
judgement.]
Subjects will return to the site for monthly injection visits every 28 days (-2 / +7 days) for a total 
of up to 6 injections. Subjects are not required to complete all 6 injections and may choose to 
“early terminate” (ET) the study at any time.
At each subsequent visit (Injection Visits 2 through 6) the following procedures and assessments 
will be performed:   urine pregnancy test for all female subjects who are of childbearing potential 
before each injection; evaluation of previous injection site for potential reaction and evidence of 
attempts to remove the depot; collection of vital signs pre- and post-injection; RBP-6000 
injection; urine drug screen (UDS); C-SSRS since last visit assessment, counseling (manual-

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guided behavioral therapy); local injection site grading; subject self-assessment of injection site 
pain (Injection site Pain VAS); use of concomitant medications; and assessment for AEs. 
Laboratory tests (hematology, chemistry and urinalysis) may be requested by the Investigator on 
an ad-hoc basis as necessary to further examine any AEs. 
Alternative treatment options should be assessed at least two months before EOS at each visit, 
however it is recommended where possible to assess at every visit.
At the EOS/ET Visit, the following procedures and assessments will be performed: urine 
pregnancy test for all female subjects who are of childbearing potential; evaluation of previous 
injection site for potential reaction and evidence of attempts to remove the depot; vital sign 
measurements; UDS; C-SSRS “since last visit” assessment, counseling (manual-guided 
behavioral therapy); use of concomitant medications; assessment for AEs; brief physical exam; 
height and body weight measurement (to determine a subject’s BMI); hip and waist 
circumference (to determine a subject’s hip-to-waist ratio); and laboratory tests (hematology, 
chemistry, urinalysis). 
Approximately 4 weeks after EOS/ET Visit, all subjects should be contacted by telephone for a 
safety follow-up assessment of AEs and use of any concomitant medications.
A schematic depicting the study design is presented in Figure 1.  A complete list of procedures 
and assessments for subjects is in the Schedule of Events (SOE) in Appendix 1.

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Figure 1
Study Overview
Note: RB-US-13-0003 EOS / Screening and RBP-6000 Injection 1 / Week 1 occurs on the same 
day (Day 1).

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3.2
Rationale for Study Design
The purpose of this study is to provide up to an additional 6 injections of RBP-6000 for those 
subjects who have completed the RB-US-13-0003 study and for whom a new treatment venue 
has not yet been identified or arranged while ensuring their use of the product is monitored for 
safety. The study design includes only monthly visits with additional safety assessments while 
the long term safety and tolerability of RBP-6000 are being studied. 
3.3
Study Duration and Dates
This will be a multiple-dose study, with the first IMP administration (RBP-6000) on Day 1. The 
expected maximum duration of participation for subjects is up to approximately 29 weeks 
consisting of a maximum 25-week open-label treatment period, and a safety follow-up phone call 
at 4 weeks after the EOS/ET Visit.
Subjects who receive at least 1 dose of RBP-6000 and discontinue the trial for any reason will be 
required to complete the EOS/ET Visit and the safety follow-up telephone call.

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4
STUDY POPULATION SELECTION
4.1
Study Population
Approximately 300 subjects will be enrolled into this study. The study population will consist of 
individuals diagnosed with OUD who are seeking treatment for opioid use disorder, and who 
have completed the EOS for RB-US-13-0003 study. 
4.2
Inclusion Criteria
Subjects who have successfully completed Study RB-US-13-0003 EOS assessments, which will 
serve as screening for this study. In addition, only the following criteria must be met to be 
enrolled in this study:
1. Provide written consent to participate in this study.
2. Completed the End of Study Visit for the RB-US-13-0003 study. 
3. Be considered eligible in the medical judgment of the Investigator.
4. Females: Women of childbearing potential (defined as all women who are not surgically 
sterile or postmenopausal for at least 1 year prior to ICF) must have a negative pregnancy 
test prior to enrollment and must agree to use a medically acceptable means of 
contraception from screening through at least 6 months after the last dose of 
investigational medicinal product (IMP).
Males: Subjects with female partners of child-bearing potential must agree to use
medically acceptable contraception after signing the ICF through at least 6 months after 
the last dose of IMP. Male subjects must also agree not to donate sperm during the study 
and for 6 months after receiving the last dose of IMP. 
The following methods of contraception are considered to be medically acceptable:  
established use (for a period of at least 1 month) of oral, injected or implanted hormonal 
contraception; placement of an intrauterine device or intrauterine system; use of a double-
barrier method of contraception (condom or occlusive cap with use of a spermicide) or 
male sterilization.  
5. Subjects must agree not to take any buprenorphine products other than those administered 
during the current study throughout participation in the study.
6. Subjects must be willing to adhere to study procedures.
4.3
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from the study:
1. Subject compliance issues during participation in the RB-US-13-0003 study which, in the 
opinion of the Investigator, could potentially compromise subject safety.
2. Women of childbearing potential who have a positive pregnancy test at the RB-US-13-
0003 EOS Visit, who are pregnant or breastfeeding, seeking pregnancy, or failing to use 
adequate contraceptive methods during the study.
3. History of suicidal ideation within 28 days prior to signing the ICF as evidenced by 
answering “yes’ to questions 4 or 5 on the suicidal ideation portion of the C-SSRS “since 

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last visit” assessment (completed in the EOS Visit for Study RB-US-13-0003); or history 
of a suicide attempt (per the C-SSRS “screening/baseline” assessment for the current 
study) in the 6 months prior to signing the ICF. 
4. Taking any cytochrome P450 3A4 and 2C8 inducers and inhibitors; self-reported 
additional buprenorphine (in addition to amount administered per protocol as part of 
subject’s participation in Study RB-US-13-0003); or OTC and/or herbal supplements 
with the potential to prolong QTc as per Section 6.10.1 within 28 days of Day 1; unless 
prior written approval is obtained from the Medical Monitor. 

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5
STUDY TREATMENTS
5.1
Description of Treatment
RBP-6000 contains buprenorphine in the ATRIGEL delivery system.  RBP-6000 is 
manufactured according to Good Manufacturing Practice standards.  RBP-6000 will be supplied 
as a single-syringe system, which is prefilled with RBP-6000.  The entire contents of the 
prefilled syringe will be administered.  (See Appendix 2: IMP Preparation and Dispensing 
Procedures for detailed dosage instructions).  
5.2
Treatments Administered
A single SC dose will be injected by an individual who is medically qualified to perform the 
procedure and delegated by the Principal Investigator to perform the task.  Injections of 
RBP-6000 will be administered in the abdominal area below the waist but above the hip bone; 
more specifically, injection should occur in the region where the body curves at the side to about 
2 inches from the middle of the abdomen with adequate amounts of subcutaneous tissue that 
does not have excessive pigment, nodules, lesions, or hair.  RBP-6000 will form a solid polymer 
depot that contains the buprenorphine.  As the depot degrades, buprenorphine will be released 
into the systemic circulation at a consistent rate over an approximately 28-day period.  For 
detailed instructions on use, see Appendix 2.
5.3
Selection and Timing of Dose for Each Subject
The study schedule is designed so that each of the injections will be separated by a minimum of 
26 days and a maximum of 35 days (28 days -2/+7 days) and will be given on alternate sides of 
the subject’s abdomen (see Appendix 2 and the Pharmacy Manual for detailed information on 
administration).  
If at an Injection Visit there is a safety concern with administration of RBP-6000, dosing can be 
delayed within the specified window. No injections are permitted outside of this window without 
prior consent from the Medical Monitor. 
Time of dose is defined as the time the RBP-6000 SC injection is complete.
5.4
Method of Assigning Subjects to Treatment Groups
There are no distinct treatment groups in this study. Doses of either 100 mg or 300 mg 
RBP-6000 may be administered to the subject, based on the medical judgment of the 
Investigator. The reason for dose change should be captured in the electronic case report form 
(eCRF)
Subjects will retain the subject number assigned to them in the RB-US-13-0003 study. The 
subject number will be recorded in the source document and eCRF.

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5.5
Blinding
Not applicable; this is an open-label study 
5.6
Restrictions
Subjects should be advised to avoid strenuous exercise. 
See section 6.10.1 for prohibited concomitant medications. 
5.7
Dosing Compliance
IMP will be administered by a designated and qualified licensed healthcare provider, unless a 
designated person is pre-approved by the Sponsor.  The time of dose and any dosing 
observations will be recorded in source documentation; in addition, time of dose will be recorded 
in the eCRF. Time of dose is defined as the time the RBP-6000 SC injection is complete.  The 
Investigator or designated individual will maintain a log of all IMPs dispensed and returned (if 
applicable).  The Investigator agrees not to supply RBP-6000 to any person except study 
personnel for SC injection of subjects in this study.  
5.8
Packaging and Labeling
RBP-6000 will be identified as an investigational compound and will be packaged and labeled in 
a manner consistent with the study design and applicable regulations.
5.9
Product Quality Complaints
Any issues noted (something out of the ordinary) with the packaging, labeling or RBP-6000 
product should be immediately reported.  Please refer to the Pharmacy Manual for detailed 
instructions.
5.10
Storage and Accountability
RBP-6000 should be stored under refrigerated conditions at 2ºC to 8ºC (36°F to 46°F).  
Temperature excursions in the range of 8°C to 25°C (46°F to 77°F) are permitted for a maximum 
duration of 48 hours; temperature excursions in the range of -20°C to 2°C (-4°F to 36°F) are 
permitted for a maximum duration of 7 days. Temperature excursions outside of this range 
should be reported to the Sponsor immediately and approval should be obtained before use, 
please refer to the pharmacy manual for details.
The Investigator or designee is responsible for ensuring that all IMP received at the site is 
inventoried and accounted for throughout the study. IMP must be handled strictly in accordance 
with the protocol, handling guidelines and the label, and must be stored in a locked, limited 
access area under appropriate environmental conditions. The Investigator must ensure that proper 
conditions exist for storage of study treatments. The dispensing of IMP to the subject must be 
documented.  Re-supply of RBP-6000 will be managed by IWRS and automatic shipments will 

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be processed based upon enrollment status and current available stock at the site (see Pharmacy 
Manual for further information on re-supply shipments).
Unused IMP must be available for verification by the site’s CRA during on-site monitoring 
visits. All used syringes components will be disposed of in accordance with the site’s standard 
operating procedure (SOP) or pharmacy destruction policy, which will be reviewed by the CRA 
before use. All used IMP packaging components should be retained for the verification by the 
CRA before disposal is permitted.
5.11
IMP Retention at Study Site
All unused RBP-6000 must be returned to the warehouse before the end of the study. The 
warehouse will arrange for the appropriate and timely destruction of all returned, unused 
RBP-6000. 

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6
STUDY PROCEDURES
The SOE for this study is provided in Appendix 1.
6.1
Medical History
A detailed medical history will be re-collected for this study up until signing the ICF. This will 
include information regarding the subject’s full history of medical and psychiatric conditions; 
diagnoses; procedures; concomitant medications; demographic information; use of tobacco, 
drugs of abuse, alcohol, and caffeine; and any other noteworthy medical information, including 
suicidality measured using the C-SSRS, hospitalizations and the reason for admission 
(medical/surgical/psychiatric/other). Any pre-planned surgeries or procedures outside of the 
scope of this study should also be considered as part of medical history. The medical history also 
should include medical events that occurred during a subject’s participation in Study RB-US-13-
0001 and/or RB-US-13-0003, and are deemed relevant in the opinion of the Principal 
Investigator. Any relevant updates to medical history information that the Investigator or 
medically-qualified designee becomes aware of during the course of the study should also be 
recorded.
Surgical procedures, planned before enrollment of the subject in the study, are not considered 
AEs if the condition was known before study inclusion.  In this case the medical condition 
should be reported in the subject’s medical history.
6.2
Physical Examination
A physical examination will be performed by the Investigator or medically qualified designee at 
the EOS Visit for study RB-US-13-0003. Assessments for general appearance, chest/lungs, heart, 
abdomen and the brief neurological assessment will serve as the screening values for the present 
study. If any clinically significant abnormal findings were observed before the INDV-6000-301 
ICF was signed (including those noted during the RB-US-13-0003 EOS), these findings should 
be recorded on the Medical History case report form (eCRF). 
A brief physical exam will be repeated at EOS for INDV-6000-301. The physical examination 
will consist of an examination of the following:  general appearance, chest/lungs, heart, abdomen 
and a brief neurological assessment.  The examination will not include a pelvic, breast, or rectal 
examination.  If any clinically significant change from screening is noted, it will be reported as 
an AE and followed up to resolution or until reaching a stable end point.
6.3
Body Mass Index and Hip-to-Waist Ratio
A subject’s weight (kg) (in ordinary indoor clothing with shoes off) will be measured at the EOS 
Visit for Study RB-US-13-0003. A subject’s height (cm) will be re-measured at the INDV-6000-
301 Screening Visit.  These measurements (weight and height) will be inputted into the eCRF in 
order to calculate a BMI (i.e., BMI calculation will be done automatically in the electronic data 
capture system).  BMI is defined as the subject’s weight in kg divided by the square of the 
subject’s height in meters (kg/m2).  (Note: Calculation of BMI in the EOS Visit for Study RB-

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US-13-0003 will use the height measurement originally taken at screening for the prior study.)  
A subject’s amount of abdominal fat (waist-to-hip ratio) will be determined using measurement 
of both waist and hip circumference (cm) at the EOS Visit for Study RB-US-13-0003; this 
previously calculated waist-to-hip ratio will be recorded in the eCRF.  These values will serve as 
the screening values for this study. The above assessments will be repeated at the EOS/ET Visit 
for INDV-6000-301, as detailed in the SOE (Appendix 1).
6.4
Vital Signs
Evaluation of vital signs will be performed after the subject has been supine for ≥ 3 minutes and 
will include a measurement of systolic and diastolic blood pressure, pulse rate, pulse oximetry, 
respiratory rate, and oral temperature.  
If clinically significant findings, as determined by the Investigator or medically qualified Sub-
investigator, occur in any vital sign measurement, that measurement will be captured as an AE 
and repeated at medically appropriate intervals until the value returns to an acceptable range, a 
specific diagnosis is established, or the condition is otherwise explained.
Assessments will be recorded in the source documents and eCRF and will be performed at the 
time points detailed in the SOE (Appendix 1).
6.5
Clinical Laboratory Tests
6.5.1
Laboratory Parameters
All clinical laboratory assessments will be performed by a clinical laboratory accredited by the 
College of American Pathologists or with a Certificate of Compliance or Accreditation (or 
Certificate of Waiver for CLIA-waived tests) issued by the Center for Medicare & Medicaid 
Services. The laboratory assessments will include routine and screening laboratory tests. 
See the SOE in Appendix 1 for the timing of the specific required laboratory tests which are 
listed in Table 2. 
Any abnormal hematology, chemistry, or urinalysis test result deemed clinically significant by 
the Investigator will be repeated.  For any test abnormality deemed clinically significant, an AE 
will be recorded (unless the result was considered erroneous) and repeat analysis will be 
performed until resolution or until the Investigator determines that resolution of the laboratory 
abnormality is not expected.  
Subjects will be in a seated or supine position during blood collection.  Clinical laboratory panels 
are listed in Table 2.

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Table 2
List of Laboratory Tests
Hematology:
Hematocrit
Hemoglobin 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Mean corpuscular volume 
Platelet count
Red blood cell count
White blood cell count with differential
Urinalysis:
Appearance
Bilirubin
Color
Glucose
Ketones
Leucocyte esterase
Microscopic examination of sedimenta
Nitrite
Occult blood
pH
Protein
Specific gravity
Urobilinogen
Pregnancy:
Urine Pregnancy (only for females not postmenopausal or 
surgically sterile for at least 1 year)
Urine Drug Screen:
Opioidsb
Cocaine
Amphetamines
Methadone
Cannabinoids
Barbiturates
Benzodiazepines
Methamphetamine
Phencyclidine
Serum Chemistry:
Albumin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Amylase
Aspartate aminotransferase (AST)
Blood urea nitrogen
Calcium
Calculated creatinine clearancec
Carbon dioxide
Chloride
Creatinine
Creatine kinase and subtypes
Gamma-glutamyl transferase
Globulin
Glucose (non-fasting)
High-density lipoprotein (HDL)
Lactate dehydrogenase
Lipase
Low-density lipoprotein (LDL)
Magnesium
Phosphorus
Potassium
Sodium
Total bilirubin
Direct bilirubin
Total cholesterol
Total protein
Triglycerides
Uric acid
a
Microscopic examination of sediment will be performed only if the results of the urinalysis evaluation are 
positive (microscopic examination may include but is not limited to WBC count, RBC count, casts, and crystals).
b
Oxycodone may not show up in all opiate assays and should be assessed separately.
c
Creatinine clearance will be calculated according to the Cockcroft-Gault equation.
6.5.2
Sample Collection, Storage, and Shipping
All blood sampling will be by individual venipuncture or with the use of a saline lock.  Blood 
and urine sample collection and processing procedures will be outlined in a separate reference 
manual to be provided to the site.

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6.5.3
Reference Ranges
Up-to-date reference ranges for the above investigations must be obtained from the laboratory 
performing analyses prior to the start of the study and be updated as appropriate during the 
course of the study.
6.5.4
Laboratory Results Review
The Investigator will review the results and comment on the laboratory results sheet for all 
abnormal values, identifying those that are abnormal but not clinically significant as well as 
those that are significantly abnormal.  The Investigator will sign and date the laboratory results 
sheet to indicate that the review has taken place.
Clinical Laboratory Changes:  It is the Investigator’s responsibility to review the results of all 
laboratory tests as they become available.  This review will be documented by the Investigator 
on the laboratory report.  For each abnormal laboratory test result, the Investigator needs to 
ascertain if this is a clinically significant abnormal change from baseline for that individual 
subject. 
Any liver abnormality > 3 x ULN should be carefully assessed by the Investigator to determine 
whether it should be considered an AE. Guidance for the procedures to follow for elevated liver 
function tests are provided in Appendix 8.
6.6
Suicidality Assessments  
The C-SSRS is a questionnaire designed for assessment of suicidal ideation and behavior in 
adolescents and adults (Posner 2011).  Suicidality assessment will be conducted according to the 
SOE table in Appendix 1, using two versions of the C-SSRS (“baseline/screening” and “since 
last visit”). The C-SSRS “baseline/screening” assessment will include both a lifetime and past 6-
month time interval.  The two C-SSRS versions are presented in Appendix 4 and Appendix 5. 
If a subject becomes suicidal during the study, the Investigator should provide appropriate 
treatment to the subject.  If the suicidality is deemed to be related to IMP and it is within 14 days 
of an injection, the depot may be removed (Section 6.12.1).
If there is a positive (“yes”) response on the C-SSRS (“since last visit”) assessment after 
screening, the subject will be evaluated by the Investigator for continuation in the study.  If 
needed, the Investigator can consult with the Medical Monitor.
6.7
Local Injection Site Tolerability
6.7.1
Injection Site Evaluation
At Injection Visits 2 through the EOS/ET Visit, the local injection site will be evaluated for 
potential reaction and evidence of any attempts to remove the depot medication following a 
previous injection of RBP-6000.  This evaluation should be performed by the Investigator or a 
trained and qualified licensed healthcare professional.  Any detected removal attempts should be 

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discussed with the Medical Monitor to determine whether the subject should be terminated from 
the study.  In addition, detection of any depot removal attempt at the EOS Visit for the prior 
study (Study RB-US-13-0003) should be discussed with the Medical Monitor to determine 
whether a subject should be enrolled into the current study.  
Depot removal attempts are to be captured in the e-CRF (using “Yes” or “No” answers). 
6.7.2
Injection Site Grading
Local injection site grading will be performed by the Investigator or a trained and qualified 
licensed healthcare professional, unless a designated person is pre-approved by the Sponsor, 
according to the SOE in Appendix 1.  Grading should be performed 1 hour (+ 30 minutes) post-
completion of injection.  Injection sites will be assessed for pain, tenderness, erythema/redness, 
induration, or swelling.  Local injection site tolerability will be assigned a severity grade, 
including none (grade 0), mild (grade 1), moderate (grade 2), severe (grade 3), or potentially life 
threatening (grade 4) utilizing the 5-point Injection Site Grading Scale in Appendix 6.
6.7.3
Injection Site Pain Visual Analog Scale (VAS) 
Injection site pain will be assessed by the subject at each Injection Visit with a 100 mm VAS 
scale ranging from 0 to 100, where 0 represents “no pain” and 100 represents “maximum pain”
(Appendix 7). The injection site pain VAS scores will be obtained approximately 1 hour after 
each injection. The timing of the injection site pain VAS assessment should be measured starting 
from the end of the injection. In addition to self-rating pain level by marking on the line the point 
they feel best represents their perception of their current state, the subject will also answer the 
following question with either a “Yes” or “No”: Are you currently experiencing any burning or 
stinging at the injection site?
Copies of any pre-printed VAS paper forms to be used by subjects for self-assessment of their 
injection site pain must be checked to confirm that the VAS rating scale measures exactly 100 
mm (3.94 in) in length.
6.8
Pharmacokinetic Assessments
Not Applicable
6.9
Adverse Events Assessments
6.9.1
Adverse Event Definition
In accordance with ICH and United States Food and Drug Administration (FDA) guidance, any 
untoward medical occurrence incurred by a subject that occurs after the first study-related 
procedure to the completion of the Safety Follow-Up Visit and is associated with the use of the 
drug, regardless of the presence of causal relationship, is a reportable AE.  AEs that are ongoing 
at the time of the RB-US-13-0003 EOS visit will be recorded in the eCRF for this study. 

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All subjects participating in the study that have a EOS/ET Visit will be contacted by telephone 
for a safety follow-up assessment of AEs (new or ongoing) and use of any concomitant 
medications. 
Abnormal results of diagnostic procedures, including laboratory test abnormalities, are 
considered AEs if they:

Result in discontinuation from the study,

Require treatment or any other therapeutic intervention,

Require further diagnostic evaluation (excluding a repetition of the same procedure to 
confirm the abnormality), or

Are associated with clinical signs or symptoms that would have a significant clinical 
impact, as determined by the Investigator.
6.9.2
Treatment-Emergent Adverse Event Definition
A TEAE is an AE that either commenced following initiation of IMP or was present prior to the 
initiation of IMP, but increased in frequency or severity following initiation of treatment, 
regardless of causality.
6.9.3
Performing Adverse Events Assessments
The Investigator is ultimately responsible for assessing and reporting all AEs as outlined in the 
protocol.  The assessment of AEs may be delegated to a medically qualified Sub-investigator, 
trained on this study protocol, who is listed on the FDA Form 1572 or equivalent document, and 
on the delegation of authority form.
AEs should be volunteered by the subject or solicited from the subject using a standard 
statement, obtained from examination of the subject at a site visit, or from observations of 
clinically significant laboratory values or special examination abnormal values.  If an event 
assessed by one of the study scales requires intervention, or if in the opinion of the Investigator, 
it is clinically significant, then it will be reported as an AE. Any ongoing AEs reported in the 
RB-US-13-0003 study will be recorded in the eCRF for this study. 
All AEs are to be assessed and recorded in a timely manner and followed to resolution or until 
the Investigator determines that there is not an anticipated resolution.  Each AE is to be 
documented with reference to severity, date of occurrence, duration, treatment, and outcome.  
Furthermore, each AE is to be classified as being serious or non-serious.  In addition, the 
Investigator must assess whether the AE is drug-related or not.
6.9.4
Timing
AEs will be captured from the time the subject gives informed consent until the subject 
completes the Safety Follow-Up Visit.   

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Surgical procedures, planned before enrollment of the subject in the study, are not considered 
AEs if the condition was known before study inclusion.  In this case the medical condition 
should be reported in the subject’s medical history (see Section 6.1).  
6.9.5
Severity
Adverse events with changes in severity should be documented as separate events.
Intensity
Definition
Mild
Causes transient or mild discomfort; no limitation of usual activities; no 
medical intervention required
Moderate
Causes mild to moderate limitation in activity; some limitation of usual 
activities: no or minimal medical intervention or therapy is required.
Severe
Causes marked limitation in activity; some assistance is usually required; 
medical intervention or therapy is required; hospitalization is probable.  
The term “severe” is used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe); the event itself, however, may be of relatively minor medical significance 
(such as a severe headache). This is not the same as “serious,” which is based on subject/event 
outcome or action criteria usually associated with events that pose a threat to a subject’s life or 
functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting 
obligations.
6.9.6
Relationship
The Investigator or a medically qualified Sub-investigator, trained on this study protocol, listed 
on the 1572 form or equivalent document and on the delegation of authority form is responsible 
for determining the AE relationship to the IMP.
The following categories will be used to define the relationship of an AE to the administration of 
the IMP:
Not Related:
Data are available to identify a clear alternative cause for the AE other than 
the IMP.
Related:
The cause of the AE is related to the investigational product and cannot be 
reasonably explained by other factors (e.g., the subject’s clinical state, 
concomitant therapy, and/or other interventions).
6.9.7
Expectedness
An unexpected AE is any AE, the nature and severity of which is not consistent with the IB for 
the IMP.

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6.9.8
Clinical Significance
The Investigator or medically qualified Sub-investigator, trained on this study protocol, listed on 
the 1572 form and on the delegation of authority form is responsible for determining clinical 
significance of abnormal assessment results (e.g., laboratory results) for the subject.
6.9.9
Clinical Laboratory Adverse Events
Changes in laboratory values or vital signs, or other safety parameters (e.g., neurological and 
clinical symptom assessments) as noted in the protocol are a subset of AEs and are reportable 
only if considered to be clinically significant by the Investigator or medically qualified Sub-
investigator except that:
•
Baseline assessments are differentiated from AE/symptoms that are incurred post 
informed consent.  These baseline lab assessments, if determined to be clinically 
significant abnormal values, reflect the status of the subject prior to study participation.  
These clinically significant pre-dose abnormal assessments without clinical symptoms 
will not be reported as AEs. 
It is noted that any liver abnormality > 3 x ULN should be carefully assessed by the Investigator 
to determine whether it should be considered an AE. Guidance for the procedures to follow for 
elevated liver function tests are provided in Appendix 8.
6.9.10
Serious Adverse Events
6.9.11
Serious Adverse Event Definition
A SAE is defined as any AE occurring at any dose that results in any of the following outcomes: 

death, 

life-threatening AE,

hospitalization or prolongation of existing hospitalization, 

a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or

a congenital anomaly or birth defect.
“Important medical events may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.” 
6.9.11.1
Suspected Unexpected Serious Adverse Event Definition
A suspected unexpected serious adverse reaction (SUSAR) is any SAE that, in its nature or 
severity, is inconsistent with available medication information (e.g., IB or Package Insert). 
Indivior Pharmacovigilance will determine if an SAE is a SUSAR.

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6.9.11.2
Reporting Serious Adverse Events
All SAEs will be reported to the Sponsor by the Investigator or designee by email or fax within 
24 hours of discovery, using the form provided by the Sponsor.  The SAE report should also be 
emailed to the Medical Monitor.
In the event of an SAE, the Investigator or designee will notify Indivior Pharmacovigilance:
Email: PatientSafetyNA@indivior.com
Fax: (804) 423-8951
Indivior Inc.
10710 Midlothian Turnpike, Suite 430
Richmond, VA 23235
In the event that medical discussion is required for an SAE, the Medical Monitor should be 
contacted:
24-hour number: 
Email: 
In the event of an emergency, a back-up has also been identified: 
 
Email: 
The Investigator or designee must inform the institutional review board (IRB) immediately 
regarding any AE (does not have to be causally related) that is both serious and unexpected 
(SUSAR); or that represents a series of AEs that on analysis is unanticipated, or occurs at an 
unanticipated frequency, or otherwise represents an unanticipated safety risk to the study subject. 
The IRB may subsequently choose to modify the informed consent or request changes to the 
protocol or IB.  
Subjects with ongoing SAEs at the Safety Follow-Up Visit that in the opinion of the Investigator 
or medically qualified Sub-investigator are associated with the study, will be followed and 
reported as described in Section 6.9.11.2.
6.9.12
Pregnancy
If a pregnancy is confirmed at any time during the study through a urine pregnancy test
performed by the study laboratory, the subject will be discontinued from the study and will 
undergo all final study visit procedures (with the exception of a urine pregnancy test). If the 
partner of a study subject becomes pregnant, the pregnancy will be reported to the clinical unit 
within 48 hours of the subject’s knowledge of the pregnancy. The Investigator will attempt to 
collect pregnancy information on any female partner of a male study subject who becomes 
pregnant while participating in this study. After obtaining the necessary signed informed consent 

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from the female partner directly, the Investigator will record pregnancy information on the 
appropriate form and submit it to Indivior or designated representative within 24 hours of 
learning of the partner’s pregnancy. 
All confirmed pregnancies that occur within this study will be followed until resolution (i.e., 
termination [voluntary or spontaneous] or birth).  
Pregnancy ([study subject or the partner of a study subject] [without associated unexpected or 
adverse sequelae]) is not a reportable AE but must be reported to the Sponsor within 24 hours of 
the Investigator or study staff first being aware of the subject’s condition. 
6.10
Concomitant Medication Assessments
The Investigator or designee will record any concomitant therapies given during the course of the 
study on the concomitant medication page of the subject’s source documentation and eCRF. Any 
changes in concomitant therapy during the study will also be documented, including cessation of 
therapy, initiation of therapy, and dose changes.
Concomitant therapies are defined as prescribed medications and over the counter (OTC) 
preparations, including herbal preparations and vitamins, other than study medication and 
supplementary medication that the subject receives within 28 days of screening and for the 
during the course of the study.  Any medication taken by the subject is to be reported by the 
subject and noted on the subject’s source document and concomitant medication page.  Any 
changes in concomitant therapy during the study will be documented, including cessation of 
therapy, initiation of therapy, and dose changes.
Subjects who are medically prescribed benzodiazepines will be evaluated on a case-by-case basis 
for inclusion in the INDV-6000-301 study.  The Investigator will discuss these subjects with the 
Medical Monitor before enrolling into the INDV-6000-301 study.
The Investigator or designee will also record any medications given for the treatment of AEs on 
the concomitant medication page.  
6.10.1
Prohibited Concomitant Medications
The sponsor must approve any prohibited concomitant medications before administration except 
in cases of immediate medical need. In cases of immediate medical need, consult the Medical 
Monitor as soon as possible following administration of a prohibited medication for any further 
questions and to ensure appropriate documentation. All concomitant medications should be 
recorded in the eCRF. 
The following medications are prohibited: 

All cytochrome P450 3A4 and 2C8 inducers and inhibitors inclusive of, but not limited to 
those in Appendix 3

Buprenorphine (in addition to RBP-6000 treatment)

OTC and/or herbal supplements with the potential to prolong QTc. (For example: 
famotidine (e.g., Pepcid brand), ephedrine, and some Chinese herbal supplements.)

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The use of all opioids should be avoided in this study.

If the subject self-medicates with these medications, document reason for use 
appropriately.

Any prescribed opioids for other uses (such as pain) should be discussed with the 
Medical Monitor.
The use of the following medications requires careful consideration, and should be discussed 
with the Medical Monitor. If treatment is necessary, careful monitoring is required for: 

prescription medications known to prolong the QTc interval

general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, and 
sedative/hypnotics.
6.11
Counseling/Behavioral Therapy
After enrollment, subjects will receive manual-guided, individual behavioral therapy according 
to the SOE indicated in Appendix 1 . Behavioral therapy can be conducted by any appropriately 
trained staff member at the site. A reference manual will be provided to each site by the Sponsor.
6.12
Removal of Subjects from the Study
Subjects will be free to withdraw at any time for any reason, or they may be withdrawn if 
necessary, to protect their health and safety or the integrity of the study data.  
The Investigator or medically qualified Sub-investigator may choose to withdraw a subject from 
the study at any time.  Reasons for removing a subject from the study may include, but are not 
limited to the following:
•
Protocol deviation that comprises or may compromise data integrity, protocol compliance, or 
subject safety;
•
AE that compromises or may compromise subject safety;

Sponsor or Investigator terminates the study;

Subject requests to be discontinued from the study (i.e., subject declines further study 
participation); or

Subject becomes pregnant.
If a subject withdraws prematurely from the study after receiving IMP, the primary reason for 
withdrawal will be documented as 1 of the above, lost to follow-up, or other in the source 
documentation. 
6.12.1
Early Removal of RBP-6000
In the event of an emergency, toxicity is suspected, or if a subject withdraws or is withdrawn 
within the first 14 days of receiving an injection of RBP-6000, subjects may have the option to 
have the depot surgically removed by a physician delegated to perform surgery. The medically 
responsible physician should carefully discuss this option with subjects and the feasibility of 

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extracting the depot. The surgical procedure requires a small incision in the abdomen where the 
depot was placed, removal of the depot with forceps, and suturing to close the incision. The 
subject should have the ET assessments performed at the time of early removal of RBP-6000 and 
a safety follow up call 28 days later, as per the SOE (Appendix 1). 
The extracted RBP-6000 depot will be disposed as per the SOPs at the clinical site.  
Detailed RBP-6000 depot removal instructions are in Appendix 2.
6.12.2
Stopping Rules
The Investigator must contact the Sponsor immediately to discuss whether to suspend dosing if 
an AE or laboratory abnormalities indicates that continued dosing of subsequent subjects would 
not be tolerated or would jeopardize the subjects’ safety.  The Sponsor alone may suspend dosing 
at any time for any reason.
Factors that must be considered for suspension of dosing include the frequency, severity, clinical 
significance, possible causality, and anticipated reversibility of all observed AEs or laboratory 
abnormalities for each specific SC injection group.  If dosing is suspended, the IRB will be 
notified in accordance with IRB requirements.
Guidance for the procedures to follow for elevated liver function tests are provided in Appendix 
8.
6.12.3
Lost to Follow-up
A subject is considered as lost to follow-up if the site has made reasonable attempts to contact 
the subject and received no response. This may be due to the subject not returning to the site, or 
not answering the safety follow-up telephone call. A minimum of 2 documented telephone calls 
followed by a certified mailed letter is considered reasonable. At that point, the subject may be 
considered lost to follow-up and any open AEs may be closed. 
6.12.4
Screen Failures
A screen failure subject is a subject that signed the ICF but did not receive IMP.
6.13
Other Study Procedures
6.13.1
Unscheduled Visits
If unscheduled visits occur, the Investigator must record the following in the subject’s source 
documentation:

Any AEs

Reason for unscheduled visit

Recording of any changes or additions to concomitant medications dose or regimen

Any clinical assessments deemed appropriate for the clinical care of the subject

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Unscheduled visits should not alter the timing of the routine study schedule.
6.14
Appropriateness of Measurements
All measurements to be obtained in this study are standard and widely used.

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7
STUDY ACTIVITIES
This study will be conducted as a fully non-residential (outpatient) study.  An overview of the 
study is shown in Figure 1.  Details on procedures/activities for this study are provided in 
Section 6 and SOE is provided in Appendix 1.

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8
QUALITY CONTROL AND ASSURANCE
8.1
Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study centers, review of protocol procedures with the Investigators 
and associated personnel before the study, periodic monitoring visits by the Sponsor, and direct 
transmission of clinical laboratory data from a central laboratory into the Sponsor’s (or 
designee’s) database.  Written instructions will be provided for IMP preparation and dosing, 
collection, preparation, and shipment of blood, plasma, and urine samples.  Guidelines for eCRF 
completion will be provided and reviewed with study personnel before the start of the study.  
The Sponsor (or designee) will review eCRFs for accuracy and completeness during on-site 
monitoring visits and after transmission to the Sponsor (or designee).  Any discrepancies will be 
resolved with the Investigator or suitably qualified designee, as appropriate.
8.2
Quality Assurance
This study will be organized, performed, and reported in compliance with the protocol, SOPs, 
working practice documents, and applicable regulations and guidelines.  
In accordance with the standards defined in Sponsor SOPs and applicable regulatory 
requirements, clinical studies sponsored by Sponsor are subject to Sponsor Quality Audits at the 
study sites that will be conducted by personnel from an appropriate unit. Site audits may be 
performed by the Sponsor’s (or contractor’s) qualified Quality Assurance (QA) team, which is an 
independent function from the study conduct team. QA audits may include review of, but are not 
limited to, drug supply, presence of required documents, the informed consent process, and 
comparison of eCRFs with source documents. The Investigator agrees to participate with QA 
audits conducted at a reasonable time in a reasonable manner. Full consultation with the 
Investigator will be made prior to and during such a QA audit, which will be conducted 
according to the Sponsor's (or contractor's) QA SOPs. In addition, this study may be subject to 
inspections by regulatory authorities. If such a regulatory inspection occurs, the Investigator 
agrees to allow the regulatory inspector direct access to all relevant study documents. The 
Investigator must contact the Sponsor immediately if this occurs and must fully cooperate with 
the inspection conducted at a reasonable time in a reasonable manner.

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9
PLANNED STATISTICAL METHODS
9.1
General Considerations
A Statistical Analysis Plan (SAP) will be prepared after the protocol is approved and before 
database lock occurs.  The SAP will provide further details regarding the definition of analysis 
endpoints, data handling rules, and the statistical methodology to be used to address all study 
objectives.  The SAP will also include formats for the summary and analysis tables, listings, and 
graphical displays.
This section describes the method for the analysis population and planned analyses.  Additional 
unplanned analyses may be required after all planned analyses have been completed.  Any 
unplanned analyses will be clearly identified in the clinical study report.  Any deviations from 
the analyses described below will be included in the SAP, which will form Appendix 16.1.9 of 
the clinical study report.
Continuous variables will be summarized using descriptive statistics such as means, standard 
deviations (SD), medians, minimums, and maximums.  Categorical variables will be reported as 
frequency counts (including number missing) and the percentage of subjects in corresponding 
categories.  Individual subject data will be presented by subject in data listings.  Data listings will 
include all data collected from the initial screening visit to the end of study for all subjects 
enrolled.  
9.2
Determination of Sample Size
All subjects who completed the RB-US-13-0003 study may be eligible to enroll into this study. 
This will be approximately 300 subjects.
9.3
Analysis Populations
The population used for all safety analyses will be comprised of all subjects who received at least 
1 dose of RBP-6000 in this study.
A completer is defined as a subject who completes the EOS visit (WK 25, Day 169). 
9.4
Demographics and Baseline Characteristics
Demographic and baseline characteristics (gender, race, age, weight, height) will be summarized 
using descriptive statistics. Qualitative variables (gender, race) will be summarized using 
frequencies while quantitative variables (age, weight, height) will be summarized using mean, 
SD, median, minimum, and maximum.
9.5
Primary Analysis
Safety variables will include AEs, local injection site tolerability (e.g., injection site grading); 
injection site pain using a subject-reported VAS; suicidality using the C-SSRS, concomitant 
medications; clinical laboratory results (hematology, chemistry and urinalysis); vital sign 

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measurements; physical examination results; body weight, height, BMI, and abdominal fat 
measurement (waist-to-hip ratio). Safety variables will be assessed with regards to the safety 
population. 
Baseline is defined as the value collected at Screening.  No imputation of missing values will be 
performed.
9.5.1.1
Adverse Events
All AEs will be coded using the most up-to-date version of the Medical Dictionary for 
Regulatory Activities (MedDRA) and reported to the FDA. AEs that began after the EOS visit 
will not be included in the safety analysis. Only TEAEs occurring post administration of 
RBP-6000 will be included in the safety analysis (See Section 6.9.2).
The incidence of AEs (number and percent of subjects reporting the AE at least once during the 
study) will be summarized for all AEs, by the relationship to IMP and by severity.
9.5.1.2
Laboratory Data
Clinical laboratory assessments are conducted at screening and at the EOS visit, summary 
statistics for the absolute laboratory value and the change from baseline will be presented.  
9.5.1.3
Vital Signs
Vital signs measurements will be assessed for clinical relevance.  
9.5.1.4
Other Variables Related to Safety
Medical history will be coded using MedDRA and summarized by treatment group as described 
for AEs (Section 9.5.1.1).  Body weight, height, BMI, and abdominal fat measurement (waist-to-
hip ratio) will be summarized using descriptive statistics (mean, median, SD, minimum, 
maximum), including change from baseline.
Total C-SSRS scores will be summarized using descriptive statistics (mean, median, SD, 
minimum, maximum), including change from baseline.  
Prior and concomitant medications will be coded using the most recent version of the World 
Health Organization (WHO) Drug dictionary.  Incidence (number and percent of subjects 
reporting the medication at least once during the study) will be summarized for all concomitant 
medications.
Local injection site tolerability as assessed by the Injection Site Grading scale will be 
summarized by category and severity using frequency counts and percentages similar to 
summaries for AEs (Section 9.5.1.1).  Injection Site Pain VAS scores will be summarized by 
dose and injection.  The burning/stinging categorical variable (Yes/No) will be summarized by 
percent of responses for each dose.

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9.6
Handling of Missing Data
Missing data will not be imputed.  
9.7
Subjects Who Withdraw from the Study
Subjects who withdraw after receiving RBP-6000 will not be replaced.
9.8
Interim Analyses
If an interim analysis were to be performed for this study the details will be outlined in the 
statistical analysis plan. 

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10 ADMINISTRATIVE CONSIDERATIONS
10.1
Investigators and Study Administrative Structure
10.1.1
Sponsor
Indivior Inc.
10710 Midlothian Turnpike, Suite 430
Richmond, VA 23235
10.1.2
Investigational Site(s)
This study will be conducted at up to 31 sites in the US.
10.1.3
Laboratories
Laboratories used for the safety laboratory tests (serum chemistry, hematology, serology, and 
urinalysis), will be conducted at a central laboratory that is certified and accredited to perform 
the assigned assessments.
10.2
Institutional Review Board Approval
The protocol will be reviewed by an independent, appropriately constituted, centralized IRB. 
Study enrolment and protocol related procedures, which do not form part of the subject’s normal 
clinical treatment, will not be performed until the IRB of record has provided written approval of 
the protocol or a modification thereof.  The IRB must be constituted and operate in accordance 
with the principles and requirements of ICH GCP.
IMP can only be supplied to the Investigator after documentation on all ethical and legal 
requirements for starting the study has been received by the Sponsor.  This documentation must 
also include an IRB membership list that contains member’s occupations.  If the IRB will not 
disclose the names of the committee members, the IRB Number may be accepted as a substitute 
for this list.  Formal approval by the IRB should mention the study title, study code, study site 
(or region or area of jurisdiction, as applicable), and any other documents reviewed.  It must 
mention the date on which the decision was made and must be officially signed by a committee 
member.
10.3
Ethical Conduct of the Study
The Investigator is responsible for ensuring that the clinical study is performed in accordance 
with the protocol, current ICH GCP guidelines, and applicable regulatory and country-specific 
requirements.  GCP is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects.  
Compliance with this standard provides the public assurance that the rights, safety, and 
well-being of study subjects are protected and that the clinical study data are credible.

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10.4
Subject Informed Consent
Prior to entering the study, the Investigator or designated individual must explain to each subject 
the nature of the study, its purpose, procedures, expected duration, alternative therapies 
available, and the benefits and risks involved in study participation. Subjects must be given the 
IRB-approved ICF to review and the opportunity to ask questions. In the case of a non-medically 
qualified person conducting the consent process, he/she must have ready access to an 
investigator to whom any questions from the study subject may be referred. Subjects must be 
informed of their right to withdraw from the study at any time without prejudice. The potential 
subjects should be able to answer simple questions about the study after the ICF has been 
reviewed and explained. After this explanation and before any study-specific procedures have 
been performed, the subject must voluntarily sign and date the ICF to indicate the desire to 
participate in the study. The Investigator or the individual designated to conduct the consent 
discussion for the Investigator must also sign and date the ICF and the time (hour and minute) 
the consent is signed must be recorded. Verbal informed consent followed by a signed consent 
short form is not acceptable to Sponsor. Prior to participation in the study, the subject must 
receive a copy of the signed and dated ICF along with an emergency card with contact 
information for the Investigator and site staff in the event of a medical emergency during the 
study.
10.5
Subject Confidentiality
All subject-identifying documentation generated in this study must be considered confidential 
and must not be disclosed to any persons not directly concerned with the study without written 
permission from the subject.  However, authorized regulatory officials and Sponsor personnel (or 
their representatives) will be allowed full access to inspect and copy the records.  All subject 
bodily fluids, and/or other materials collected shall be used solely in accordance with this 
protocol and the ICF signed by the subject, unless otherwise agreed to in writing by the Sponsor.
Each subject will be identified by initials and an assigned subject number when reporting study 
information to any entity outside of the study center. Data containing subject identification must 
not be removed from the site without subject identifiers having been redacted.
10.6
Study Monitoring
In accordance with applicable regulations, GCP, and Sponsor procedures, the CRA will 
periodically contact the site, including conducting on-site visits at intervals agreed by the 
Investigator and documented in the Clinical Monitoring Plan and the Site Initiation Visit Report.  
The CRA will contact the site prior to the start of the study to discuss the protocol and data 
collection procedures with site personnel. In accordance with applicable regulations and GCP 
guidelines, the Investigator must make available for direct access all study-related records upon 
request of the Sponsor, the Sponsor’s agents, CRA, auditors, and/or IRB. The Sponsor’s CRAs 
will visit the site during the study in addition to maintaining frequent telephone and written 
communication. The extent, nature, and frequency of on-site visits will be based on such 

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considerations as the study objectives and/or endpoints, the purpose of the study, study design 
complexity, and enrolment rate. 
The Investigator must allow the clinical monitor(s) direct access to all relevant documents and to 
allocate his/her time and the time of his/her staff to the clinical monitor(s) to discuss findings and 
any relevant issues.
10.6.1
Study and Site Closure
Upon completion of the study, study closeout activities must be conducted by the Sponsor or its 
designee in conjunction with the Investigator, as appropriate.
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 
the Investigator (including the reason[s] for taking such action) at that time.  The Sponsor will 
also 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 must inform the 
IRB promptly and provide the reason(s) for the suspension or termination.  If the study is 
prematurely discontinued, all study data and IMP remaining on site must be returned to the 
Sponsor or its designee.
10.7
Case Report Forms and Study Records
The Investigator is responsible for the quality of the data recorded in the eCRFs.  The data 
recorded should be a complete and accurate account of the subject’s record collected during the 
study.  Study data are not to be gathered directly onto the eCRF but must be gathered onto 
primary source documents at the clinical site. Completion of source documents will precede the 
completion of the eCRF.  Source documents may be electronic, hard copy, or a combination of 
both.  Source documents are defined as the results of original observations and activities of a 
clinical investigation. Source documents will include, but are not limited to, progress notes, 
electronic data, screening logs, and recorded data from automated instruments. All source 
documents pertaining to this study will be maintained by the investigators and made available for 
direct inspection by the authorized study personnel outlined in the ICF. Site staff will receive 
training on the eCRF completion guidelines and requirements for source documentation which 
will provided by Sponsor or its designee.  
Completed eCRFs will be reviewed by the CRA in line with eCRF completion guidelines for the 
study to ensure completeness and consistency.  The clinical monitoring plan for this study will 
define the level of source data verification required.  Any discrepancies found during the eCRF 
review will be clarified by the Investigator or designated individual.  This includes eCRF 
reviews at the site by Sponsor or its designee, or during quality assurance review of the data.  
An explanation must be documented for any missing data.  Any changes to information in the 
study progress notes and other source documents will be initialed and dated on the day the 
change is made by a site staff member authorized to make the change.  Changes will be made by 
striking a single line through erroneous data (so as not to obliterate the original data), and clearly 
entering the correct data (e.g., wrong data right data).  If the reason for the change is not 

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apparent, a brief explanation for the change will be written in the source documentation by the 
site.
The Investigator must sign and date a declaration attesting to his/her responsibility for the quality 
of all data recorded, and that the data represents a complete and accurate record of each subject’s 
participation in the study.  
All eCRF entries, corrections, and alterations must be made by the Investigator or designated 
individual.  The Investigator or designated individual must adjust the eCRF (if applicable) and 
complete the query.
10.8
Data Monitoring Committee
Not applicable; there will be no data monitoring committee for this study.
10.9
Protocol Deviations
This study is intended to be conducted as described in this protocol. At the outset of the study, a 
process for defining and handling protocol deviations will be established. This will include 
determining which deviations will be designated “important” and require immediate notification 
to the Sponsor. In the event of a deviation from the protocol due to an emergency, accident, or 
mistake, the Investigator or designated individual must contact the Sponsor at the earliest 
possible time by telephone. This will allow an early joint decision regarding the subject’s 
continuation in the study. This decision will be documented by the Investigator and the Sponsor, 
and reviewed by the CRA. All deviations from the protocol must be documented. The 
Investigator or designated individual will be responsible for identifying and reporting all 
deviations, which are defined as isolated occurrences involving a procedure that did not follow 
the study protocol or study-specific procedure. Deviations will be reported as required to the IRB 
and in the final study report.
10.10 Access to Source Documentation
The Investigator must agree to complete a subject identification and enrolment log to permit easy 
identification of each subject during and after the study.  This document will be reviewed by the 
CRA for completeness.  The subject identification and enrollment log will be treated as 
confidential and will be filed by the Investigator in the study center file.  To ensure subject 
confidentiality, no copy will be made.  All reports and communications relating to the study will 
identify subjects by initials and assigned number only.  The Investigator must also complete a 
subject-screening log, which reports on all subjects who were seen to determine eligibility for 
inclusion in the study.
At a minimum, source documentation must be available for the following to confirm data 
collected in the eCRF: subject identification, eligibility, and study identification; study 
discussion and date of informed consent; dates of visits; results of safety and efficacy parameters 
as required by the protocol; record of all AEs; concomitant medications; IMP administered; date 
of study completion or early discontinuation, and reason for early discontinuation if applicable.

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10.11 Data Generation and Analysis
10.11.1 Data Collection and Data Management
Study specific data that has been outlined in the protocol will be entered into the clinical 
database by individual(s) designated by the Investigator in accordance with the eCRF 
Completion Guidelines.  Data is verified electronically using a series of on-line programmed edit 
checks that have been created by the Clinical Data Manager and programmed by the Clinical 
Data Programmer or Designee.  Data discrepancies will be brought to the attention of the clinical 
team and investigated by the CRA and Site Study Coordinator.  CRAs will review and verify all 
data collected in the eCRF against source documentation as defined in the clinical monitoring 
plan.  The CRA will work closely with the Site Study Coordinator to address any discrepancies 
which have been found so that proper resolutions can be made and documented into the clinical 
database.  An audit trail within the system will track all changes made to the data.
10.11.2 Database Quality Assurance 
The clinical database will be reviewed and checked for omissions, apparent errors, and values 
requiring further clarification using computerized and manual procedures.  Data queries 
requiring clarification will be generated and addressed by the investigational site.  Only 
authorized personnel will make corrections to the clinical database, and all corrections will be 
documented in an audit trail.  
10.12 Retention of Data
All documents pertaining to the study, including all versions of the approved study protocol, 
copy of the ICF document and Health Insurance Portability and Accountability Act documents, 
completed eCRFs, source documents (subject records, subject diaries, hospital records, 
laboratory records, drug accountability records, etc.), and other study-related documents will be 
retained in the permanent archives of the study site.
The Investigator must therefore notify and obtain approval in writing from the Sponsor prior to 
destruction of any study records or provide an opportunity for the Sponsor to collect such 
records.  If the investigator withdraws from the study (e.g., relocation, retirement) all study-
related records should be transferred, in a written agreement with the Sponsor, to a mutually 
agreed upon designee within a Sponsor-specified timeframe.
10.13 Financial Disclosure
The Sponsor requires, for each study, the disclosure of any financial interests from each 
investigator or sub-investigator, including financial interests of the spouse and each dependent 
child of the investigator who is directly involved in the treatment or evaluation of research 
subjects that could affect the reliability of data submitted to regulatory authorities. The collection 
of this financial interest information at the start of the study, as well as any updates should this 
information change, is required by the FDA when submitting a marketing application and is in 
line with the GCP requirement to consider any potential conflicts of interest.

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10.14 Publication and Disclosure Policy
A clinical study report will be prepared following completion of the study.  The report will be a 
record of the total study conduct and will be subject to Sponsor approval and restrictions on 
distribution/disclosure.
The study data will be owned by the Sponsor.  Publication of any and all data will be at the 
discretion of the Sponsor.  The Investigator will not disseminate, present, or publish any of the 
study data without the prior written approval of the Sponsor to do so.

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11 REFERENCE LIST
American Psychiatric Association (2013).  Diagnostic and Statistical Manual of Mental 
Disorders (5th edition).
Department of Justice, Economic Impact of Illicit Drug Use in American Society, 2011.
Drug Interaction Information: http://medicine.iupui.edu/clinpharm/ddis/clinical-table/. Accessed 
30 September 2016.
Indivior RBP-6000 Investigator's Brochure, Edition 5. 18 May 2016.
Nasser AF, Heidbreder C, Gomeni R, et al (2014).  A population pharmacokinetic and 
pharmacodynamic modelling approach to support the clinical development of RBP-6000, a new, 
subcutaneously injectable, long-acting, sustained-release formulation of buprenorphine, for the 
treatment of opioid dependence. Clin Pharmacokinet. DOI 10.1007/s40262-014-0155-0
Posner K, Brown GK, Stanley B, et al (2011).  The Columbia-suicide severity rating scale: initial 
validity and internal consistency findings from three multisite studies with adolescents and 
adults. Am J Psychiatry. 168 (12): 1266-77.
RB-US-10-0011, Reckitt Benckiser Pharmaceuticals Internal report (2011). A Single-Dose, 
Open-Label Study of Depot Buprenorphine (RBP-6000) in Opioid-Dependent Individuals.
RB-US-11-0020, Reckitt Benckiser Pharmaceuticals Internal report (2013). A Multicenter, 
Open-Label, Single Ascending-Dose Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of Depot Buprenorphine (RBP-6000) in Opioid-Dependent Subjects.
RB-US-12-0005, Reckitt Benckiser Pharmaceuticals Internal report (2015), An Open-Label, 
Multicenter, Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, Efficacy 
Markers, and Opioid Receptor Availability of Subcutaneous Injections of Depot Buprenorphine 
(RBP-6000) in Treatment Seeking Opioid-Dependent Subjects 
RB-US-13-0002, Reckitt Benckiser Pharmaceuticals Internal report (2015), A Multiple-Dose 
Study of Blockade of Subjective Opioid Effects, Pharmacokinetics, and Safety of Subcutaneous 
Injections of Depot Buprenorphine (RBP-6000) in Subjects with Opioid Use Disorder
U.S. Department of Health and Human Services, Food and Drug Administration, Center for 
Biologics Evaluation and Research, September 2007.  Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials. [pdf] Available at: 
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInform
ation/Guidances/Vaccines/ucm091977.pdf.  Accessed 30 September 2016. 

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Appendix 1 
Schedule of Events  
Procedure/Evaluation 
Screening1 
Inj 1 
Inj 2 
Inj 3 
Inj 4 
Inj 5 
Inj 6 
EOS/ 
ET 
Safety 
Follow-Up15 
EOS Visit 
RB-US-13-0003 
Screening Visit 
INDV-6000-301 
Day 1 
Week 1 
Day 29 
Week 5 
Day 57 
Week 9 
Day 85 
Week 13 
Day 113 
Week 17 
Day 141 
Week 21 
Day 169 
Week 25 
Day 197 
Week 29 
Window (Days) 
- - - - - - - - - Same Day Events3 - - - - - - - - - 
-2 / +7 
-2 / +7 
-2 / +7 
-2 / +7 
-2 / +7 
-2 / +7 
-2 / +7 
Informed Consent 2 
 
X 
 
 
 
 
 
 
 
 
IWRS 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
Medical History 
 
X 
 
 
 
 
 
 
 
 
Inclusion / Exclusion Criteria 
 
X 
 
 
 
 
 
 
 
 
Vital Signs 4 
X 
 
X 5 
X 
X 
X 
X 
X 
X 
 
Urine Pregnancy Test 6 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Urine Drug Screen 7 
X 
 
 
X 
X 
X 
X 
X 
X 
 
AE Assessment  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
C-SSRS 8 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Injection Site Evaluation 9 
X 
 
 
X 
X 
X 
X 
X 
X 
 
RBP-6000 Injection 
 
 
X 
X 
X 
X 
X 
X 
 
 
Injection Site Grading Scale 10 
 
 
X 
X 
X 
X 
X 
X 
 
 
Injection Site Pain VAS 10 
 
 
X 
X 
X 
X 
X 
X 
 
 
Counseling / Behavioral Therapy 
X 
 
 
X 
X 
X 
X 
X 
X 
 
Review of Treatment Options12 
 
 
 
 
 
 
X 
X 
X 
 
Physical Examination13 
X 
 
 
 
 
 
 
 
X 
 
Body Weight 
X 
 
 
 
 
 
 
 
X 
 
Height 
 
X 
 
 
 
 
 
 
 
 
BMI (calculated in CRF) 
 
X 
 
 
 
 
 
 
X 
 
Hip and Waist Circumference 
X 
 
 
 
 
 
 
 
X 
 
Hip-to-Waist Ratio (calculated in CRF) 
 
X 
 
 
 
 
 
 
X 
 

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Procedure/Evaluation
Screening1
Inj 1
Inj 2
Inj 3
Inj 4
Inj 5
Inj 6
EOS/
ET
Safety
Follow-Up15
EOS Visit
RB-US-13-0003
Screening Visit
INDV-6000-301
Day 1
Week 1
Day 29
Week 5
Day 57
Week 9
Day 85
Week 13
Day 113
Week 17
Day 141
Week 21
Day 169
Week 25
Day 197
Week 29
Window (Days)
- - - - - - - - - Same Day Events3 - - - - - - - - -
-2 / +7
-2 / +7
-2 / +7
-2 / +7
-2 / +7
-2 / +7
-2 / +7
Hematology / Serum Chemistry 14
X
X
Urinalysis 14
X
X
AE = adverse event; BMI = body mass index; C-SSRS = Columbia Suicide Severity Rating Scale; EOS = End of Study; ET = Early Termination; Inj. = injection; 
IWRS=Interactive voice/web response system; NA = Not Applicable; VAS = Visual Analog Scale.
1.
All indicated screening assessments conducted during the RB-US-13-0003 EOS Visit will be used as part of the overall screening process for the present 
study.  However, required assessments indicated under “Screening Visit INDV-6000-301” must only be performed after the ICF is signed.
2.
The ICF may be shared with the subject up to 2 months before the EOS Visit for RB-US-13-0003 study in order to discuss this new study as a possible 
treatment option. However, the ICF for this study must not be signed until all assessments for the RB-US-13-0003 EOS Visit are complete.
3.
The Screening Visit assessments and Day 1 injection must occur on the same day as the RB-US-13-0003 EOS Visit. 
4.
Includes blood pressure, pulse oximetry, pulse rate, respiratory rate, and oral temperature which must be taken after subject is supine ≥ 3 minutes. With 
the exception of Day 1, vital signs will be taken ≤ 60 minutes prior to injection, and 1 hour (± 30 minutes) post-completion of injection. 
5.
On Day 1, vital signs are only required to be collected 1 hour (± 30 minutes) post-completion of injection; the screening value will serve as the pre-
injection value.
6.
Only for female subjects who are of childbearing potential (not postmenopausal or surgically sterile for at least 1 year).
7.
Oxycodone may not show up in all opiate assays and should be assessed separately.
8.
At the EOS Visit for Study RB-US-13-0003, the C-SSRS “since last visit” (e-PRO) version will be used for confirming exclusion 3 only.  In addition, as 
part of the Screening Visit for INDV-6000-301, the C-SSRS “baseline/screening” (paper) version will be required to be completed; on all other visits, 
the “since last visit” (paper) version should be used.  The C-SSRS “baseline/screening” assessment will include both a lifetime and past 6-month time 
interval.  
9.
Injection site will be evaluated for potential reaction and evidence of attempted removal before the next injection of RBP-6000 is administered.  
10. Local injection site grading will be performed 1 hour (± 30 minutes) post-completion of injection.
11. Injection Site Pain VAS will be completed by the subject 1 hour (± 30 minutes) post-completion of injection.
12. Subject’s alternative treatment options should be assessed at least two months before EOS, however it is recommended to review at each visit.
13. Brief physical examination including general appearance, chest/lungs, heart, abdomen and a brief neurological assessment.
14. Additional unscheduled labs may be added at the Investigator’s discretion in order to fully assess any AEs.
All subjects should receive a safety follow-up contact. Subjects should be contacted by telephone in order to inquire about any new AEs, or a stop date 
for any ongoing AEs or concomitant medications. They are not required to return to the site, unless the Investigator deems it medically necessary. In the 
event a subject cannot be contacted for the follow-up telephone contact, a minimum of 2 documented telephone calls followed by a certified mailed 
letter will be considered a reasonable effort for contacting the subject. If follow-up contact with a subject cannot be made, any open AEs will be 
designated as “ongoing.”

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Appendix 2
IMP Preparation, Administration, and Depot Removal 
Instructions
RBP-6000 PREPARATION AND DOSING PROCEDURE

100 MG BUPRENORPHINE

300 MG BUPRENORPHINE
IMPORTANT:  Only qualified study personnel can prepare the IMP. Protective gloves (latex 
or nitrile) should be worn when preparing and dosing RBP-6000.  Remove the product from the 
refrigerator at least 15 minutes before use to allow the product to reach room temperature before 
dosing.  Product may be left at room temperature up to 8 hours prior to use.  If product is not 
used that day, it should be marked appropriately.  
  
FOLLOW THE INSTRUCTIONS AS DIRECTED TO ENSURE PROPER DOSING
Preparation of the Product Prior to Administration: 
The following components will be used in the preparation of RBP-6000:
•
One sealed foil pouch containing a syringe pre-filled with RBP-6000 and an oxygen 
absorber pack. 
•
One sterile 19-gauge, 1- or 5/8-inch hypodermic safety needle
1. On a clean field, open the foil pouch and remove the contents. Discard the oxygen absorber 
pack. The pouch must be retained for accountability.
2. Un-cap the pre-filled RBP-6000 syringe and attach the safety needle cartridge by pushing in 
and turning the needle until it is finger tight. Do not strip the threaded fitting by over-
tightening the needle. Position the sheath at 90 degrees to the needle.  Pull off the needle 
cartridge cover.   More complete documentation on the usage of the SurGuard2 safety needle 
can be found in the included instruction sheet. 
3. While holding the syringe vertically with the tip upwards, expel air bubbles by stroking the 
plunger up and down.
4. The product is now ready for administration.  Carefully recap the needle.
Administration Procedure:
IMPORTANT: Once prepared (removed from foil pouch), the product must be 
administered within a maximum of 30 minutes.
Choose an injection site below the waist but above the hip bone; from where the body curves at 
the side to about 2 inches from the middle of the abdomen with adequate amounts of 
subcutaneous tissue that does not have excessive pigment, nodules, lesions, or hair.  Since you 
can vary the injection site with a subcutaneous injection, choose an area that has not recently 
been used.  

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Possible injection site locations and an injection rotation pattern are shown in Figure 2.  
Injections should be started based on where the last injection in RB-US-13-0003 was given.
Figure 2
Injection Locations
1. Cleanse the injection-site area with an alcohol swab.  
2. Using the thumb and forefinger of your non-dominant hand, grab and bunch the area of skin 
around the injection site.
3. Using your dominant hand, insert the needle quickly. If a 1-inch needle is used, enter half the 
length, if a 5/8-inch needle is used the needle may be inserted fully. The approximate angle 
you use will depend on the amount and fullness of the subcutaneous tissue and the length of 
the needle.
4. After the needle is inserted, release the skin with your non-dominant hand.
5. Pull back on the plunger to check for blood.  If blood is present in the syringe, do not inject.  
Withdraw the needle and dispose of syringe and needle in an appropriate waste container.  
Repeat the “Preparation of the Product Prior to Administration” procedures and the 
“Administration Procedure” using a different abdominal injection site with another syringe 
of RBP-6000 and associated components.
6. Inject the product using a slow, steady push. Press down on the plunger until the syringe is 
empty.
7. Withdraw the needle at the same angle used for insertion. Do not rub the injection area.  If 
there is bleeding, apply minimal pressure with a gauze pad or bandage.  Engage the safety 
sheath on the needle as per the SurGuard2 needle instructions.  
8. Dispose of used and unused syringe and needle in an appropriate waste container. 
Hipbones
Waist
1 / 5
2 / 6
3
4

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PROCEDURE FOR REMOVAL OF THE RBP-6000 DEPOT
In the event of an emergency or if a subject withdraws or is withdrawn within the first 14 days of 
receiving an injection of RBP-6000, subjects may have the option to have the depot surgically 
removed by a physician delegated to perform surgery. The medically responsible physician 
should carefully discuss this option with subjects given the use of ATRIGEL Delivery System 
and the feasibility of extracting the depot.
The following surgical procedure should be followed:
1.
Palpate the depot and surrounding area to confirm its exact location.
2.
Cleanse the area with an antiseptic solution (e.g., Betadine).  
3.
Infiltrate the area with a local anesthesia (e.g., Lidocaine 1% or a lidocaine/adrenaline 
[epinephrine] mixture) and wait for it to take effect.
4.
Cover the area with a sterile drape.
5.
Incise the skin up to the subcutaneous tissues using a scalpel. 
6.
Using blunt and sharp dissection, identify the plane between the depot and surrounding 
subcutaneous tissues.  Once the plane is identified, separate the superficial 25% of the 
circumference of the depot with blunt dissection. 
7.
Gently lift the incised ellipse of skin and depot with forceps.  
8.
Once the depot is removed, ensure hemostasis, and close the skin with non-absorbable 
sutures.  
9.
The extracted RBP-6000 depot will be disposed of into an appropriate, secure biohazard 
container per the SOP at the clinical site.

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Appendix 3
Prohibited Cytochrome P450 Inhibitors and Inducers
Cytochrome P450 3A4 Inhibitors
Name
Example Brand Name(s)
Name
Example Brand Name(s)
Amiodarone
Cordarone, Nexterone
Ketoconazole
Nizoral
Amprenavir
Agenerase, 
Metronidazole
Flagyl
Aprepitant
Emend
Mibefradil
Posicor
Chloramphenicol
Chloromycetin
Miconazole
Oravig
Cimetidine
Tagamet
Mifepristone
Mifeprex, Korlym
Ciprofloxacin
Ciloxan, Cipro
Nefazodone
Serzone
Clarithromycin
Biaxin
Nelfinavir
Viracept
Clotrimazole
Lotrimin
Nicardipine
Cardene
Cyclosporine
Neoral, Sandimmune
Norfloxacin
Noroxin
Delavirdine
Rescriptor
Norfluoxetine
Seproxetine (discontinued)
Diethyl-
dithiocarbamate
(zinc chelator used in cancer, 
no other name)
Propofol
Diprivan
Diltiazem
Cardizem, Dilacor 
Quinine
Qualaquin
Ethinyl estradiol
Apri, Aviane, Beyaz
Ritonavir
Norvir
Erythromycin
Erythrocin
Saquinavir
Invirase
Fluconazole
Diflucan
Sertraline
Zoloft
Fluoxetine
Prozac
Starfruit
Carambola, fruit of Averrhoa 
carambola
Fluvoxamine
Luvox
Telithromycin
Ketek
Gestodene
Progestogen hormonal 
contraceptive. 
Not available in the US. 
Troleandomycin
Not available in the US
Grapefruit juice
Grapefruit juice
Verapamil
Isoptin
Imatinib
Gleevec
Voriconazole
Vfend
Indinavir
Crixivan
Zafirlukast
Accolate
Itraconazole
Sporanox

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Cytochrome P450 3A4 Inducers
Name
Example Brand Name(s)
Name
Example Brand Name(s)
Barbiturates
   Nembutal, Luminal
Phenytoin
Dilantin, Phenytek
Carbamazepine
Carbatrol, TEGretol
Pioglitazone
Actos
Dexamethasone
Decadron
Primidone
Mysoline
Efavirenz
Sustiva, Atripla
Rifabutin
Mycobutin
Ethosuximide
Zarontin
Rifampin
Rifadin, Rimactane
Glucocorticoids
Prednisone, Medrol, 
Millipred
Hypericum 
perforatum
Medicinal herb 
Glutethimide
Doriden (Not available in 
US), Elrodorm, Noxyron.
Sulfadimidine
Not available in the US
Modafinil
Provigil
Sulfinpyrazone
Anturane
Nevirapine
Viramune
Troglitazone
Rezulin, Resulin 
Non available in US
Oxcarbazepine
Trileptal, Oxtellar XR 
Troleandomycin
Tao 
Not available in the US
Phenobarbital
Luminal 
Cytochrome P450 2C8 Inhibitors
Name
Example Brand Name(s)
Name
Example Brand Name(s)
Gemifibrozil
Lopid
Montelukast
Singulair
Trimethoprim
Primsol, Proloprim
Quercetin
Plant pigment (flavonoid)
Glitazones
Actos, Avandia
Cytochrome P450 2C8 Inducer
Name
Example Brand Name(s)
Name
Example Brand Name(s)
Rifampicin
Rifadin
Source:  http://medicine.iupui.edu/clinpharm/ddis/clinical-table/ Accessed 30 September 2016. 

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Appendix 4
Columbia Suicide Severity Rating Scale (C-SSRS) --
Baseline/Screening Version

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Note:  Screening assessment should include both a lifetime and “past 6-month” time interval.  

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Appendix 5
Columbia Suicide Severity Rating Scale (C-SSRS) --  
Since Last Visit Version

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Appendix 6
Injection Site Grading Scale
Injection site 
Reactions
None
(Grade 0)
Mild
(Grade 1)
Moderate
(Grade 2)
Severe
(Grade 3)
Potentially Life
Threatening
(Grade 4)
Pain
None
Does not 
interfere with 
activity
Repeated use of non-
narcotic pain reliever 
> 24 hours or 
interferes with activity 
Any use of narcotic 
pain reliever or 
prevents daily 
activity
Emergency room 
(ER) visit or 
hospitalization 
Tenderness
None
Mild discomfort 
to touch.
Discomfort with 
movement.
Significant 
discomfort at rest 
ER visit or 
hospitalization
Erythema/
Redness*
(quantitative)
None
2.5 – 5 cm
5.1 – 10 cm
> 10 cm
Necrosis or
exfoliative 
dermatitis
Induration **
None
2.5 – 5 cm and 
does not interfere 
with activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
Swelling **
(subjective)
None
2.5 – 5 cm and 
does not interfere 
with activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
* In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
Modified from:  
U.S. Department of Health and Human Services, Food and Drug Administration, Center for 
Biologics Evaluation and Research, September 2007.  Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials. [pdf] Available at: 
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInform
ation/Guidances/Vaccines/ucm091977.pdf.  Accessed 30 September 2016. 

RBP-6000
Indivior Inc.
Clinical Study Protocol: INDV-6000-301
Amendment 1:  30 September 2016
Page 63 of 67
Confidential
No Pain
Pain as bad 
as it could be
Appendix 7
Injection Site Pain Visual Analog Scale
How would you rate your injection site pain today?
             
Please answer the following question by checking the box with either a “Yes” or “No”:
Are you currently experiencing any burning or stinging at the injection site?
YES  
NO
Note:   Copies of any pre-printed VAS forms to be completed by a subject must be checked to 
confirm that the rating scale measures 100 mm (3.94 in) in length.

RBP-6000
Indivior Inc.
Clinical Study Protocol: INDV-6000-301
Amendment 1:  30 September 2016
Page 64 of 67
Confidential
Appendix 8
Elevated Liver Function Tests 
Elevated liver functions tests meeting one of the following criteria below must follow the 
outlined procedures. 
Criteria 1
ALT ≥3X ULN and <5X ULN 
+ Bilirubin <2X ULN
+ DO NOT exhibit hepatitis symptoms or rash

Contact the Indivior Medical Monitor within 24 hours of learning of the abnormality to 
discuss subject safety.

Subject may continue study treatment, if liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) can be monitored weekly for up to 4 weeks.

If the subject later meets criteria 2 or 3, immediately withdraw study treatment, perform 
additional testing and continue safety follow–up until liver chemistries resolve, stabilize 
or return to baseline values.

After 4 weeks of monitoring, if ALT <3XULN and bilirubin <2XULN, subject must be 
monitored twice monthly until liver chemistries normalize or return to within baseline 
values.
Criteria 2
ALT ≥5X ULN 
or 
ALT ≥3X ULN 
+ Hepatitis symptoms or rash 
+ cannot be monitoring for 4 weeks or have elevations that persist ≥4 weeks

Subject must not receive any further injections of RBP-6000. 

Contact the Indivior Medical Monitor within 24 hours of learning of the abnormality to 
discuss subject safety and any addition laboratory testing required. 

Make every reasonable attempt to have the subject return to the clinic within 24-72 hours 
for repeat liver chemistries and additional testing.

Monitor subject weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilize or return to within baseline values.

RBP-6000
Indivior Inc.
Clinical Study Protocol: INDV-6000-301
Amendment 1:  30 September 2016
Page 65 of 67
Confidential

Upon completion of the safety follow-up, the subject must be withdrawn from the study 
unless further follow–up is required.
Criteria 3
ALT ≥3X ULN + Bilirubin ≥2X ULN (>35% direct)
or
ALT ≥3X ULN + INR >1.5:
Note: INR testing is not required per protocol and the threshold value does not apply to 
subjects receiving anticoagulants.

Subject must not receive any further injections of RBP-6000. 

Contact the Indivior Medical Monitor within 24 hours of learning of the abnormality to 
discuss subject safety and any addition laboratory testing required. 

Make every reasonable attempt to have the subject return to the clinic within 24 hours for 
repeat liver chemistries, additional testing and close monitoring (with specialist or 
hepatology consultation recommended).

Monitor the subject twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilize or return to within baseline values.

Upon completion of the safety follow-up, the subject must be withdrawn from the study 
unless further follow–up is required.

RBP-6000
Indivior Inc.
Clinical Study Protocol: INDV-6000-301
Amendment 1:  30 September 2016
Page 67 of 67
Confidential
Appendix 10
Investigator’s Signature
Study Title:
An Open-Label, Depot Buprenorphine (RBP-6000) Treatment 
Extension Study in Subjects with Opioid Use Disorder
Study Number:
INDV-6000-301
Original Protocol: 
Amendment 1:
24 June 2016
30 September 2016
I have read the protocol described above. I agree to comply with all applicable regulations and to 
conduct the study as described in the protocol.  
Signed:
Date:
Printed Name and Credentials:
Title:
Site Name:
Address:
Telephone: