Treatment Seeking Participants With Opioid Use Disorders Assessing Tolerability of Depot Injections of Buprenorphine

Sponsor

Indivior Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02357901

Collaborator

(none)

665

Enrollment

Locations

Arms

Actual Duration (Months)

17.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo controlled, multicenter study in male and female participants who are seeking treatment for opioid use disorder.

Condition or Disease	Intervention/Treatment	Phase
Opioid Dependence Opioid Related Disorders	Drug: SUBOXONE Drug: RBP-6000 Drug: Placebo	Phase 3

Detailed Description

After completing an up to 2-week screening period, subjects entered an open-label run-in induction phase with SUBOXONE (buprenorphine/naloxone) sublingual film for 3 days followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information.

This is a 24-week non-residential study with participants being randomized after meeting randomization criteria. On Day 1 and Day 29 (± 2 days) participants will receive subcutaneous injections of 300 mg RBP-6000 or placebo. Thereafter, participants will receive 4 injections (once every 28 days ± 2 days) of either 300 mg or 100 mg RBP-6000 doses or placebo.

Study Design

Study Type:

Interventional

Actual Enrollment :

665 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 28, 2015

Actual Primary Completion Date :

Apr 29, 2016

Actual Study Completion Date :

Apr 29, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RBP-6000 300mg/100mg During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 are separated by 28 days (Day 57-Day 141) and contain RBP-6000 100 mg. In addition, participants received individual drug counseling (IDC) at least once a week.	Drug: SUBOXONE SUBOXONE (buprenorphine sublingual film) is used for induction therapy. Participants take sublingual film for 3 days according to the sublingual film prescribing information; they then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to randomization. Following randomization, SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Other Names: buprenorphine Sublingual Film Drug: RBP-6000 Six injections administered subcutaneously every 28 days on alternate sides of participant's abdomen at either 300 mg or 100 mg dose. Other Names: Buprenorphine
Experimental: RBP-6000 300mg/300mg During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. In addition, participants received individual drug counseling (IDC) at least once a week.	Drug: SUBOXONE SUBOXONE (buprenorphine sublingual film) is used for induction therapy. Participants take sublingual film for 3 days according to the sublingual film prescribing information; they then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to randomization. Following randomization, SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Other Names: buprenorphine Sublingual Film Drug: RBP-6000 Six injections administered subcutaneously every 28 days on alternate sides of participant's abdomen at either 300 mg or 100 mg dose. Other Names: Buprenorphine
Placebo Comparator: Placebo Matching 300 mg/100 mg RBP-6000 During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given placebo injections on Days 1 and 29 (matching the RBP-6000 300 mg dose volume). Injections 3-6 are separated by 28 days (Day 57-Day 141) and also contain placebo (matching the RBP-6000 100 mg volume). In addition, participants received individual drug counseling (IDC) at least once a week.	Drug: SUBOXONE SUBOXONE (buprenorphine sublingual film) is used for induction therapy. Participants take sublingual film for 3 days according to the sublingual film prescribing information; they then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to randomization. Following randomization, SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Other Names: buprenorphine Sublingual Film Drug: Placebo Six injections of placebo administered subcutaneously every 28 days on alternate sides of participant's abdomen at volumes matching the experimental drug. Other Names: Volume-matched placebo
Placebo Comparator: Placebo Matching 300 mg RBP-6000 During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given six placebo injections (volume-matched to RBP-6000 300 mg dose) on Days 1 to 141 with injections separated by 28 days. In addition, participants received individual drug counseling (IDC) at least once a week.	Drug: SUBOXONE SUBOXONE (buprenorphine sublingual film) is used for induction therapy. Participants take sublingual film for 3 days according to the sublingual film prescribing information; they then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to randomization. Following randomization, SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Other Names: buprenorphine Sublingual Film Drug: Placebo Six injections of placebo administered subcutaneously every 28 days on alternate sides of participant's abdomen at volumes matching the experimental drug. Other Names: Volume-matched placebo

Outcome Measures

Primary Outcome Measures

Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24 [Weekly from Weeks 5-24]
Data represent the count of participants at various percentage abstinence levels. Abstinence was defined as urine samples being negative for opioids AND negative self-reports (obtained from Timeline Followback (TLFB) interviews) for illicit opioid use. The primary endpoint was based on visits in which paired urine samples and self-reports were expected for each subject as specified in the schedule of events. Missing urine drug screen(s) (UDS) samples and/or self-reports were considered as non-negative.

Secondary Outcome Measures

Percentage of Participants Considered A Treatment Success [Weeks 5-24]
Treatment success is defined as a participant having ≥80% of urine samples negative for opioids combined with self-reports negative for illicit opioid use between weeks 5-24.
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 [Weekly from Weeks 5-24]
Data represent the count of participants at various percentage levels in which urine samples tested negative for opioids. All missing reports for urine samples were considered non-negative.
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 [Weekly from Weeks 5-24]
Data represent the count of participants at various percentage levels in which self-reports were negative for illicit use of opioids. Self-reports were obtained from Timeline Followback (TLFB) interviews. All missing self-reports were considered non-negative.
Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures [Baseline: Day 1 (prior to dosing), Weeks 5-24]
The opioid craving scale was a 100 mm scale with 0= 'no craving' on the left end and 100= 'strongest craving ever' on the right end of the scale. Participants marked where along the scale reflected their craving for opioids. The full range of the change from baseline scale was therefore 100 (no craving at baseline, strongest craving during study) to -100 (strongest craving at baseline, no craving during study). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The opioid craving VAS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Negative change from baseline values indicate a lessening of craving symptoms. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
Participants Who Complete the Week 24 Visit ("Completers") [Week 24]
A completer was defined as a participant who completed either the urine drug screen (UDS) or Timeline Followback (TLFB) assessment at the Week 24 visit.
Participants Who Are Abstinent at Week 24 [Week 24]
Participants with both a negative urine sample and negative self-report for illicit opioid use at Week 24.
Change From Baseline in the Clinical Global Impression - Improvement Scale (CGI-I) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures [Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169]
The CGI-I was used to rate the change in clinical status since the start of the treatment on an ordinal scale ranging from 1 (very much improved; nearly all better; good level of functioning; minimal symptoms; represents a very substantial change) to 7 (very much worse; severe exacerbation of symptoms and loss of functioning). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Measurements taken during the treatment period were taken at the end of each 28 day treatment and prior to dosing of the next treatment. Negative change from baseline values indicate an improved clinical global impression. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
Change From Baseline in the Clinical Global Impression - Severity Scale (CGI-S) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures [Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169]
The CGI-S was an assessment completed by the clinician to rate the severity of symptoms on an ordinal scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill subjects; pathology drastically interferes in many life functions). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Measurements taken during the treatment period were taken at the end of each 28 day treatment and prior to dosing of the next treatment. Negative change from baseline values indicate an improvement in the severity of symptoms. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures [Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169]
COWS is an 11-item instrument used to assess signs and symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderately severe withdrawal, and 37-48 severe withdrawal. Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The COWS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate.
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures [Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169]
The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The SOWS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate.
Total Number of Weeks of Abstinence as Assessed From Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24 [Weeks 5 through 24]
The total number of weeks of abstinence was assessed from urine samples negative for opioids combined with self-reports negative for illicit opioid use collected from week 5 through week 24. All missing reports for opioids were considered non-negative.
Participants With Adverse Events During the Treatment Period [Day 1 through Week 24]
Treatment-emergent adverse event (TEAE) = any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent one of the outcomes listed in this definition.
Worst Injection Site Pain From Injections 1-6 as Measured by Participant-Reported Visual Analog Scale (VAS) [Days 1, 29, 57, 85, 113, 141]
Injection site pain as measured by participant-reported VAS The participant-reported VAS for injection site pain was measured on a 100 mm scale with 'no pain' on the left end and 'strongest pain ever' on the right end of the scale (total scale of 0-100). Participants marked where along the scale reflected their localized injection pain. The injection site pain VAS scores were obtained (after the completion of the injection) within 1 minute and at 5, 10, 15, 30, 60 and 120 minutes (+- 5 minutes). The timing of the injection site pain VAS should have been measured from the end of the injection. Data represents the worst pain recorded for each participant across all 6 injections and all VAS records. The mean value is presented.
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 [Weekly - Week 2 through Week 24]
The C-SSRS asks questions of study participants regarding whether they had suicidal ideation and/or suicidal behavior since the last visit using the electronic version of the scale. The C-SSRS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder
By medical history has met DSM-5 criteria for moderate or severe opioid use disorder for the 3 months immediately prior to signing the informed consent form
Is seeking medication-assisted treatment for opioid use disorder
Is an appropriate candidate for opioid partial-agonist medication-assisted treatment in the opinion of the investigator or medically responsible physician
Body mass index (BMI) of ≥ 18.0 to ≤ 35.0 kg/m^2

Exclusion Criteria:

Current diagnosis other than opioid use disorder requiring chronic opioid treatment
Current substance use disorder as defined by DSM-5 criteria with regard to any substances other than opioids, cocaine, cannabis, tobacco, or alcohol.
Positive urine drug screen (UDS) result at screening for cocaine or cannabis AND meets DSM-5 criteria for either moderate or severe cocaine or cannabis use disorder, respectively
Meets DSM-5 criteria for moderate or severe alcohol use disorder
Received medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine) in the 90 days prior to providing written informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Haleyville Clinical Research	Haleyville	Alabama	United States	35565
2	Boyett Health Services	Hamilton	Alabama	United States	35570
3	Woodland International Research Group	Little Rock	Arkansas	United States	72211
4	Collaborative Neuroscience Network	Garden Grove	California	United States	92845
5	Behavioral Research Specialists	Glendale	California	United States	91206
6	Synergy Clinical Research Center	National City	California	United States	91950
7	North County Clinical Research	Oceanside	California	United States	92056
8	Artemis Institute for Clinical Research	San Diego	California	United States	92103
9	Care Practice	San Francisco	California	United States	94103
10	Southern California Research	Thousand Oaks	California	United States	91360
11	Amit Vijapura	Jacksonville	Florida	United States	32256
12	Meridien Research	Lakeland	Florida	United States	38805
13	Innovative Clinical Research	Lauderhill	Florida	United States	33319
14	Florida Clinical Research Center	Maitland	Florida	United States	32751
15	Try Research	Maitland	Florida	United States	32751
16	Scientific Clinical Research	North Miami	Florida	United States	33161
17	Research Centers of America	Oakland Park	Florida	United States	33334
18	Behavioral Health Care Associates	Schaumburg	Illinois	United States	60194
19	Phoenix Medical Research	Prairie Village	Kansas	United States	66206
20	Louisiana Research Associates	New Orleans	Louisiana	United States	70114
21	Louisiana Clinical Research	Shreveport	Louisiana	United States	71101
22	Stanley Street Treatment and Resources	Fall River	Massachusetts	United States	02720
23	Adams Clinical Trials	Watertown	Massachusetts	United States	02472
24	Precise Research Centers, Inc.	Flowood	Mississippi	United States	39232
25	St Louis Clinical Trials	Saint Louis	Missouri	United States	63141
26	Altea Research	Las Vegas	Nevada	United States	89102
27	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
28	Neuro-behavioral Clinical Research	Canton	Ohio	United States	44718
29	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
30	Charak Clinical Research Center	Garfield Heights	Ohio	United States	44125
31	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma	United States	73112
32	Pahl Pharmaceutical Professionals	Oklahoma City	Oklahoma	United States	73112
33	CODA	Portland	Oregon	United States	97214
34	Tipton Medical and Diagnostic Center aka Clinical Research Associates of Central PA	Altoona	Pennsylvania	United States	16602
35	UPenn Treatment Research Center	Philadelphia	Pennsylvania	United States	19104
36	Carolina Clinical Trials	Charleston	South Carolina	United States	29407
37	Pillar Clinical Research	Dallas	Texas	United States	75243
38	InSite Clinical Research	DeSoto	Texas	United States	75115

Sponsors and Collaborators

Indivior Inc.

Investigators

Study Director: Director Global Clinical Development, Indivior Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Indivior Inc.

ClinicalTrials.gov Identifier:

NCT02357901

Other Study ID Numbers:

RB-US-13-0001

First Posted:

Feb 6, 2015

Last Update Posted:

Feb 20, 2018

Last Verified:

Feb 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Opioid-Related Disorders

Buprenorphine

Buprenorphine, Naloxone Drug Combination

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	A total of 36 sites in the United States screened subjects in this study. Three sites did not randomize any subjects. Analyses of RB-US-13-0001 were planned, conducted, and reported with pooled placebo groups.

Arm/Group Title	Run-In Period	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	During the Run-In Period, participants were inducted onto SUBOXONE sublingual film followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information.	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Period Title: Run-In Period (Days -14 to Day -1)
STARTED	665	0	0	0
COMPLETED	504	0	0	0
NOT COMPLETED	161	0	0	0
Period Title: Run-In Period (Days -14 to Day -1)
STARTED	0	203	201	100
Safety Analysis Set	0	203	201	100
Full Analysis Set	0	194	196	99
COMPLETED	0	125	129	34
NOT COMPLETED	0	78	72	66

Baseline Characteristics

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo	Total
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Total of all reporting groups
Overall Participants	203	201	100	504
Age, Customized (Count of Participants)
>=18 to <30 years	44 21.7%	45 22.4%	23 23%	112 22.2%
>=30 to <45 years	88 43.3%	95 47.3%	45 45%	228 45.2%
>=45 to <60 years	64 31.5%	53 26.4%	30 30%	147 29.2%
>= 60 years	7 3.4%	8 4%	2 2%	17 3.4%
Sex: Female, Male (Count of Participants)
Female	67 33%	66 32.8%	35 35%	168 33.3%
Male	136 67%	135 67.2%	65 65%	336 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 6.4%	18 9%	10 10%	41 8.1%
Not Hispanic or Latino	190 93.6%	183 91%	90 90%	463 91.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 2%	1 0.5%	1 1%	6 1.2%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	57 28.1%	55 27.4%	20 20%	132 26.2%
White	140 69%	144 71.6%	78 78%	362 71.8%
More than one race	2 1%	1 0.5%	1 1%	4 0.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Tobacco use (Count of Participants)
Yes	187 92.1%	186 92.5%	93 93%	466 92.5%
No	16 7.9%	15 7.5%	7 7%	38 7.5%
Caffeine use (Count of Participants)
Yes	187 92.1%	185 92%	95 95%	467 92.7%
No	16 7.9%	16 8%	5 5%	37 7.3%
Alcohol use (Count of Participants)
Yes	160 78.8%	160 79.6%	81 81%	401 79.6%
No	43 21.2%	41 20.4%	19 19%	103 20.4%
Drug use history (Count of Participants)
Opioids	203 100%	201 100%	100 100%	504 100%
Cocaine	94 46.3%	80 39.8%	42 42%	216 42.9%
Amphetamines/ Methamphetamine	53 26.1%	29 14.4%	19 19%	101 20%
Methadone	25 12.3%	14 7%	5 5%	44 8.7%
Cannabinoids	113 55.7%	95 47.3%	53 53%	261 51.8%
Barbiturates	3 1.5%	1 0.5%	0 0%	4 0.8%
Buprenorphine	20 9.9%	16 8%	6 6%	42 8.3%
Benzodiazepines	25 12.3%	20 10%	13 13%	58 11.5%
Phencyclidine	0 0%	2 1%	1 1%	3 0.6%
Other	2 1%	6 3%	1 1%	9 1.8%

Outcome Measures

1. Primary Outcome

Title	Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24
Description	Data represent the count of participants at various percentage abstinence levels. Abstinence was defined as urine samples being negative for opioids AND negative self-reports (obtained from Timeline Followback (TLFB) interviews) for illicit opioid use. The primary endpoint was based on visits in which paired urine samples and self-reports were expected for each subject as specified in the schedule of events. Missing urine drug screen(s) (UDS) samples and/or self-reports were considered as non-negative.
Time Frame	Weekly from Weeks 5-24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
>=0%	194 95.6%	196 97.5%	99 99%
>=10%	139 68.5%	126 62.7%	11 11%
>=20%	115 56.7%	111 55.2%	7 7%
>=30%	101 49.8%	101 50.2%	6 6%
>=40%	90 44.3%	90 44.8%	6 6%
>=50%	86 42.4%	82 40.8%	4 4%
>=60%	78 38.4%	70 34.8%	4 4%
>=70%	66 32.5%	67 33.3%	2 2%
>=80%	55 27.1%	57 28.4%	2 2%
>=90%	41 20.2%	48 23.9%	2 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	significance at the 0.025 level
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	significance at the 0.025 level
	Method	Wilcoxon rank-sum test
	Comments

2. Secondary Outcome

Title	Percentage of Participants Considered A Treatment Success
Description	Treatment success is defined as a participant having ≥80% of urine samples negative for opioids combined with self-reports negative for illicit opioid use between weeks 5-24.
Time Frame	Weeks 5-24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
Number [percentage of participants]	28.4 14%	29.1 14.5%	2.0 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24
Description	Data represent the count of participants at various percentage levels in which urine samples tested negative for opioids. All missing reports for urine samples were considered non-negative.
Time Frame	Weekly from Weeks 5-24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
>=0%	194 95.6%	196 97.5%	99 99%
>=10%	140 69%	129 64.2%	17 17%
>=20%	120 59.1%	114 56.7%	9 9%
>=30%	106 52.2%	109 54.2%	8 8%
>=40%	97 47.8%	98 48.8%	7 7%
>=50%	91 44.8%	88 43.8%	6 6%
>=60%	82 40.4%	74 36.8%	5 5%
>=70%	73 36%	69 34.3%	4 4%
>=80%	64 31.5%	61 30.3%	4 4%
>=90%	47 23.2%	51 25.4%	2 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	Wilcoxon rank-sum test
	Comments

4. Secondary Outcome

Title	Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24
Description	Data represent the count of participants at various percentage levels in which self-reports were negative for illicit use of opioids. Self-reports were obtained from Timeline Followback (TLFB) interviews. All missing self-reports were considered non-negative.
Time Frame	Weekly from Weeks 5-24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
>=0%	194 95.6%	196 97.5%	99 99%
>=10%	163 80.3%	162 80.6%	37 37%
>=20%	155 76.4%	152 75.6%	29 29%
>=30%	139 68.5%	139 69.2%	24 24%
>=40%	132 65%	132 65.7%	20 20%
>=50%	125 61.6%	125 62.2%	18 18%
>=60%	120 59.1%	117 58.2%	17 17%
>=70%	108 53.2%	112 55.7%	14 14%
>=80%	102 50.2%	101 50.2%	9 9%
>=90%	92 45.3%	91 45.3%	7 7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	Wilcoxon rank-sum test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	Wilcoxon rank-sum test
	Comments

5. Secondary Outcome

Title	Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures
Description	The opioid craving scale was a 100 mm scale with 0= 'no craving' on the left end and 100= 'strongest craving ever' on the right end of the scale. Participants marked where along the scale reflected their craving for opioids. The full range of the change from baseline scale was therefore 100 (no craving at baseline, strongest craving during study) to -100 (strongest craving at baseline, no craving during study). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The opioid craving VAS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Negative change from baseline values indicate a lessening of craving symptoms. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
Time Frame	Baseline: Day 1 (prior to dosing), Weeks 5-24

Outcome Measure Data

Analysis Population Description
Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	192	193	96
Least Squares Mean (Standard Error) [units on a scale]	2.1 (1.63)	-0.9 (1.63)	11.5 (2.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-9.4
	Confidence Interval	(2-Sided) 95% -14.56 to -4.30
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.62
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-12.4
	Confidence Interval	(2-Sided) 95% -17.51 to -7.28
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.61
	Estimation Comments

6. Secondary Outcome

Title	Participants Who Complete the Week 24 Visit ("Completers")
Description	A completer was defined as a participant who completed either the urine drug screen (UDS) or Timeline Followback (TLFB) assessment at the Week 24 visit.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
Count of Participants [Participants]	119 58.6%	126 62.7%	33 33%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	stratified by site

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	stratified by site

7. Secondary Outcome

Title	Participants Who Are Abstinent at Week 24
Description	Participants with both a negative urine sample and negative self-report for illicit opioid use at Week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
Count of Participants [Participants]	71 35%	87 43.3%	2 2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	stratified by site

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	stratified by site

8. Secondary Outcome

Title	Change From Baseline in the Clinical Global Impression - Improvement Scale (CGI-I) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures
Description	The CGI-I was used to rate the change in clinical status since the start of the treatment on an ordinal scale ranging from 1 (very much improved; nearly all better; good level of functioning; minimal symptoms; represents a very substantial change) to 7 (very much worse; severe exacerbation of symptoms and loss of functioning). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Measurements taken during the treatment period were taken at the end of each 28 day treatment and prior to dosing of the next treatment. Negative change from baseline values indicate an improved clinical global impression. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
Time Frame	Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description
Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	169	173	60
Least Squares Mean (Standard Error) [units on a scale]	1.6 (0.11)	1.5 (0.11)	2.4 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95% -0.96 to -0.46
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95% -1.12 to -0.62
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.13
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in the Clinical Global Impression - Severity Scale (CGI-S) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures
Description	The CGI-S was an assessment completed by the clinician to rate the severity of symptoms on an ordinal scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill subjects; pathology drastically interferes in many life functions). Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Measurements taken during the treatment period were taken at the end of each 28 day treatment and prior to dosing of the next treatment. Negative change from baseline values indicate an improvement in the severity of symptoms. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
Time Frame	Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description
Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	166	170	59
Least Squares Mean (Standard Error) [units on a scale]	-0.7 (0.13)	-0.7 (0.13)	-0.0 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95% -0.89 to -0.33
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.14
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95% -0.97 to -0.41
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.14
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures
Description	COWS is an 11-item instrument used to assess signs and symptoms of opioid withdrawal (Wesson et al., 1999). The score is the sum of the responses for a total range of 0-48. The COWS is commonly used by clinicians treating patients with buprenorphine to monitor the severity of withdrawal. COWS scores below 5 are considered not indicative of withdrawal. Scores from 5 to 12 are considered mild withdrawal; from 13 to 24 moderate withdrawal; 25 to 36 moderately severe withdrawal, and 37-48 severe withdrawal. Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The COWS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate.
Time Frame	Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169

Outcome Measure Data

Analysis Population Description
Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	191	192	96
Least Squares Mean (Standard Error) [units on a scale]	-0.5 (0.22)	-1.1 (0.21)	-0.1 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3143
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95% -1.13 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.38
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0101
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95% -1.72 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.38
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures
Description	The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the participant rates on a scale of 0 (not at all) to 4 (extremely) for a full scale of 0 (no withdrawal symptoms) to 64 (extreme withdrawal symptoms). Negative change from baseline values indicate a lessening of withdrawal symptoms. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. The SOWS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21. Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate.
Time Frame	Baseline: Day 1 (prior to dosing), Baseline: Day 1 (prior to dosing), Days 2, 8, 5, 22, 29, 30, 36, 43, 50, 57, 58, 64, 71, 78, 85, 86, 92, 99, 106, 113, 114, 120, 127, 134, 141, 142, 148, 155, 162, 169

Outcome Measure Data

Analysis Population Description
Full analysis set of participants who had available data on baseline score and change from baseline in any visit through week 24.

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	192	193	96
Least Squares Mean (Standard Error) [units on a scale]	-0.9 (0.51)	-2.0 (0.51)	0.7 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0726
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95% -3.29 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.87
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments	Change from baseline was analyzed using a mixed model for repeated measures (MMRM) with terms for treatment, visit, and treatment-by-visit interaction as factors and baseline value as a covariate. Center was included in the model as a random effect.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0028
	Comments	Significance level of 0.05.
	Method	mixed model for repeated measures
	Comments

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95% -4.32 to -0.90
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.87
	Estimation Comments

12. Secondary Outcome

Title	Total Number of Weeks of Abstinence as Assessed From Urine Samples Negative for Opioids Combined With Self-Reports Negative for Illicit Opioid Use Collected From Week 5 Through Week 24
Description	The total number of weeks of abstinence was assessed from urine samples negative for opioids combined with self-reports negative for illicit opioid use collected from week 5 through week 24. All missing reports for opioids were considered non-negative.
Time Frame	Weeks 5 through 24

Outcome Measure Data

Analysis Population Description
Full analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	194	196	99
Least Squares Mean (Standard Error) [weeks]	8.5 (0.68)	8.5 (0.68)	1.0 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/100mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	ANOVA
	Comments	a random effects ANOVA model with treatment included as fixed effect and center as random effect.

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	7.5
	Confidence Interval	(2-Sided) 95% 5.81 to 9.20
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.86
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	RBP-6000 300mg/300mg, Combined Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significance level of 0.05.
	Method	ANOVA
	Comments	a random effects ANOVA model with treatment included as fixed effect and center as random effect.

Method of Estimation	Estimation Parameter	LSM difference
	Estimated Value	7.5
	Confidence Interval	(2-Sided) 95% 5.82 to 9.21
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.86
	Estimation Comments

13. Secondary Outcome

Title	Participants With Adverse Events During the Treatment Period
Description	Treatment-emergent adverse event (TEAE) = any untoward medical occurrence that develops or worsens in severity after dispensation of the study drug and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= a marked limitation in activity. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent one of the outcomes listed in this definition.
Time Frame	Day 1 through Week 24

Outcome Measure Data

Analysis Population Description
Safety analysis set

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	203	201	100
>=1 TEAE	155 76.4%	134 66.7%	56 56%
>=1 TEAE related to study drug	67 33%	70 34.8%	23 23%
>=1 serious TEAE	4 2%	7 3.5%	5 5%
>=1 serious study treatment-related TEAE	0 0%	0 0%	0 0%
Death	0 0%	1 0.5%	0 0%
>=1 severe TEAE	15 7.4%	13 6.5%	4 4%
TEAE leading to study treatment discontinuation	7 3.4%	10 5%	2 2%

14. Secondary Outcome

Title	Worst Injection Site Pain From Injections 1-6 as Measured by Participant-Reported Visual Analog Scale (VAS)
Description	Injection site pain as measured by participant-reported VAS The participant-reported VAS for injection site pain was measured on a 100 mm scale with 'no pain' on the left end and 'strongest pain ever' on the right end of the scale (total scale of 0-100). Participants marked where along the scale reflected their localized injection pain. The injection site pain VAS scores were obtained (after the completion of the injection) within 1 minute and at 5, 10, 15, 30, 60 and 120 minutes (+- 5 minutes). The timing of the injection site pain VAS should have been measured from the end of the injection. Data represents the worst pain recorded for each participant across all 6 injections and all VAS records. The mean value is presented.
Time Frame	Days 1, 29, 57, 85, 113, 141

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	202	201	100
Mean (Standard Deviation) [units on a scale]	55.8 (27.07)	63.3 (29.33)	61.0 (28.79)

15. Secondary Outcome

Title	Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24
Description	The C-SSRS asks questions of study participants regarding whether they had suicidal ideation and/or suicidal behavior since the last visit using the electronic version of the scale. The C-SSRS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21.
Time Frame	Weekly - Week 2 through Week 24

Outcome Measure Data

Analysis Population Description
Safety analysis set of participants who completed a C-SSRS during the treatment period.

Arm/Group Title	RBP-6000 300mg/100mg	RBP-6000 300mg/300mg	Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.	Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
Measure Participants	202	200	98
Suicidal Ideation: Wish to be dead	15 7.4%	11 5.5%	9 9%
Non-specific active suicidal thoughts	6 3%	1 0.5%	2 2%
(subset of above) No plan nor intent to act	2 1%	0 0%	1 1%
(subset of above) Non-specific plan, some intent	3 1.5%	0 0%	1 1%
(subset of above) Specific plan and intent	0 0%	0 0%	0 0%
Suicidal Behaviour: Preparatory acts or behaviour	0 0%	0 0%	0 0%
Aborted attempt	1 0.5%	1 0.5%	1 1%
Interrupted attempt	1 0.5%	1 0.5%	1 1%
Actual attempt	0 0%	0 0%	0 0%

Adverse Events

	RBP-6000 300mg/100mg		RBP-6000 300mg/300mg		Combined Placebo
Time Frame	Day 1 to Week 24
Adverse Event Reporting Description

Arm/Group Title	RBP-6000 300mg/100mg		RBP-6000 300mg/300mg		Combined Placebo
Arm/Group Description	Participants were given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 were separated by 28 days (Day 57-Day 141) and contained RBP-6000 100 mg. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.		Participants were given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.		Participants randomized to either of the two placebo treatment arms were combined into this one treatment arm for reporting purposes. Analyses of 13-0001 were planned, conducted, and reported with pooled placebo groups. These participants were given six volume-matched placebo injections on Days 1 to 141 with injections separated by 28 days. As of protocol Amendment 2 (21 August 2015) SUBOXONE sublingual film use was tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. In addition, participants received individual drug counseling (IDC) at least once a week.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Serious Adverse Events
	RBP-6000 300mg/100mg		RBP-6000 300mg/300mg		Combined Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/203 (2%)		7/201 (3.5%)		5/100 (5%)
Cardiac disorders
Acute myocardial infarction	1/203 (0.5%)		0/201 (0%)		0/100 (0%)
Gastrointestinal disorders
Food poisoning	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
General disorders
Drug withdrawal syndrome	0/203 (0%)		0/201 (0%)		1/100 (1%)
Hernia	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Hepatobiliary disorders
Cholelithiasis	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Infections and infestations
Abscess limb	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Extradural abscess	0/203 (0%)		0/201 (0%)		1/100 (1%)
Injury, poisoning and procedural complications
Gun shot wound	0/203 (0%)		2/201 (1%)		0/100 (0%)
Accidental overdose	0/203 (0%)		0/201 (0%)		1/100 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma	1/203 (0.5%)		0/201 (0%)		0/100 (0%)
Nervous system disorders
Myelomalacia	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Psychiatric disorders
Suicidal ideation	0/203 (0%)		0/201 (0%)		1/100 (1%)
Renal and urinary disorders
Renal impairment	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/203 (0.5%)		0/201 (0%)		1/100 (1%)
Pulmonary embolism	1/203 (0.5%)		0/201 (0%)		0/100 (0%)
Vascular disorders
Hypotension	0/203 (0%)		1/201 (0.5%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	RBP-6000 300mg/100mg		RBP-6000 300mg/300mg		Combined Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/203 (47.8%)		84/201 (41.8%)		27/100 (27%)
Gastrointestinal disorders
Constipation	19/203 (9.4%)		16/201 (8%)		0/100 (0%)
Nausea	18/203 (8.9%)		16/201 (8%)		5/100 (5%)
Vomiting	19/203 (9.4%)		11/201 (5.5%)		4/100 (4%)
General disorders
Injection site pruritus	13/203 (6.4%)		19/201 (9.5%)		4/100 (4%)
Injection site pain	10/203 (4.9%)		12/201 (6%)		3/100 (3%)
Fatigue	8/203 (3.9%)		12/201 (6%)		3/100 (3%)
Infections and infestations
Upper respiratory tract infection	15/203 (7.4%)		12/201 (6%)		1/100 (1%)
Nasopharyngitis	11/203 (5.4%)		10/201 (5%)		1/100 (1%)
Investigations
Blood creatine phosphokinase increased	11/203 (5.4%)		5/201 (2.5%)		1/100 (1%)
Nervous system disorders
Headache	19/203 (9.4%)		17/201 (8.5%)		6/100 (6%)
Psychiatric disorders
Insomnia	13/203 (6.4%)		17/201 (8.5%)		11/100 (11%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Proposed publications shall be submitted to Sponsor 30 days prior to submission for publication, and may be withheld for an additional period, up to 90 days, to allow Sponsor to file patent applications. If a multi-center publication isn't submitted for publication within 12 months of the conclusion of the Study at all sites, or is published in a shorter period, the results from the institution's site may be published individually.

Results Point of Contact

Name/Title	Global Director, Clinical Development
Organization	Indivior, Inc.
Phone	804-379-1090
Email

Responsible Party:

Indivior Inc.

ClinicalTrials.gov Identifier:

NCT02357901

Other Study ID Numbers:

RB-US-13-0001

First Posted:

Feb 6, 2015

Last Update Posted:

Feb 20, 2018

Last Verified:

Feb 1, 2018

Treatment Seeking Participants With Opioid Use Disorders Assessing Tolerability of Depot Injections of Buprenorphine

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact