Trial Outcomes & Findings for Treatment Seeking Participants With Opioid Use Disorders Assessing Tolerability of Depot Injections of Buprenorphine (NCT NCT02357901)

Last Updated: 2018-02-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

665 participants

Primary outcome timeframe

Weekly from Weeks 5-24

Results posted on

2018-02-20

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Run-In Period 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.	RBP-6000 300mg/100mg 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.	RBP-6000 300mg/300mg 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.	Combined Placebo 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.
Run-In Period (Days -14 to Day -1) STARTED	665	0	0	0
Run-In Period (Days -14 to Day -1) COMPLETED	504	0	0	0
Run-In Period (Days -14 to Day -1) NOT COMPLETED	161	0	0	0
Treatment Period (Day 1 to Week 24) STARTED	0	203	201	100
Treatment Period (Day 1 to Week 24) Safety Analysis Set	0	203	201	100
Treatment Period (Day 1 to Week 24) Full Analysis Set	0	194	196	99
Treatment Period (Day 1 to Week 24) COMPLETED	0	125	129	34
Treatment Period (Day 1 to Week 24) NOT COMPLETED	0	78	72	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Run-In Period 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.	RBP-6000 300mg/100mg 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.	RBP-6000 300mg/300mg 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.	Combined Placebo 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.
Run-In Period (Days -14 to Day -1) Run-In failures	161	0	0	0
Treatment Period (Day 1 to Week 24) Lost to Follow-up	0	26	23	12
Treatment Period (Day 1 to Week 24) Withdrawal by Subject	0	20	21	18
Treatment Period (Day 1 to Week 24) Lack of Efficacy	0	3	5	18
Treatment Period (Day 1 to Week 24) Adverse Event	0	6	10	2
Treatment Period (Day 1 to Week 24) Protocol Violation	0	2	5	0
Treatment Period (Day 1 to Week 24) Withdrawal symptoms	0	1	1	3
Treatment Period (Day 1 to Week 24) Non-compliance with study drug	0	2	0	2
Treatment Period (Day 1 to Week 24) Subject withdrawn by investigator	0	1	0	3
Treatment Period (Day 1 to Week 24) Physician Decision	0	0	1	1
Treatment Period (Day 1 to Week 24) site closed by sponsor, incarceration...	0	17	6	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RBP-6000 300mg/100mg n=203 Participants 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.	RBP-6000 300mg/300mg n=201 Participants 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.	Combined Placebo n=100 Participants 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 n=504 Participants Total of all reporting groups
Age, Customized >=18 to <30 years	44 Participants n=5 Participants	45 Participants n=7 Participants	23 Participants n=5 Participants	112 Participants n=4 Participants
Age, Customized >=30 to <45 years	88 Participants n=5 Participants	95 Participants n=7 Participants	45 Participants n=5 Participants	228 Participants n=4 Participants
Age, Customized >=45 to <60 years	64 Participants n=5 Participants	53 Participants n=7 Participants	30 Participants n=5 Participants	147 Participants n=4 Participants
Age, Customized >= 60 years	7 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Female	67 Participants n=5 Participants	66 Participants n=7 Participants	35 Participants n=5 Participants	168 Participants n=4 Participants
Sex: Female, Male Male	136 Participants n=5 Participants	135 Participants n=7 Participants	65 Participants n=5 Participants	336 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	18 Participants n=7 Participants	10 Participants n=5 Participants	41 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	190 Participants n=5 Participants	183 Participants n=7 Participants	90 Participants n=5 Participants	463 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	57 Participants n=5 Participants	55 Participants n=7 Participants	20 Participants n=5 Participants	132 Participants n=4 Participants
Race (NIH/OMB) White	140 Participants n=5 Participants	144 Participants n=7 Participants	78 Participants n=5 Participants	362 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Tobacco use Yes	187 Participants n=5 Participants	186 Participants n=7 Participants	93 Participants n=5 Participants	466 Participants n=4 Participants
Tobacco use No	16 Participants n=5 Participants	15 Participants n=7 Participants	7 Participants n=5 Participants	38 Participants n=4 Participants
Caffeine use Yes	187 Participants n=5 Participants	185 Participants n=7 Participants	95 Participants n=5 Participants	467 Participants n=4 Participants
Caffeine use No	16 Participants n=5 Participants	16 Participants n=7 Participants	5 Participants n=5 Participants	37 Participants n=4 Participants
Alcohol use Yes	160 Participants n=5 Participants	160 Participants n=7 Participants	81 Participants n=5 Participants	401 Participants n=4 Participants
Alcohol use No	43 Participants n=5 Participants	41 Participants n=7 Participants	19 Participants n=5 Participants	103 Participants n=4 Participants
Drug use history Opioids	203 Participants n=5 Participants	201 Participants n=7 Participants	100 Participants n=5 Participants	504 Participants n=4 Participants
Drug use history Cocaine	94 Participants n=5 Participants	80 Participants n=7 Participants	42 Participants n=5 Participants	216 Participants n=4 Participants
Drug use history Amphetamines/ Methamphetamine	53 Participants n=5 Participants	29 Participants n=7 Participants	19 Participants n=5 Participants	101 Participants n=4 Participants
Drug use history Methadone	25 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	44 Participants n=4 Participants
Drug use history Cannabinoids	113 Participants n=5 Participants	95 Participants n=7 Participants	53 Participants n=5 Participants	261 Participants n=4 Participants
Drug use history Barbiturates	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Drug use history Buprenorphine	20 Participants n=5 Participants	16 Participants n=7 Participants	6 Participants n=5 Participants	42 Participants n=4 Participants
Drug use history Benzodiazepines	25 Participants n=5 Participants	20 Participants n=7 Participants	13 Participants n=5 Participants	58 Participants n=4 Participants
Drug use history Phencyclidine	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Drug use history Other	2 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Weekly from Weeks 5-24

Population: Full analysis set

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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.
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 >=0%	194 Participants	196 Participants	99 Participants
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 >=10%	139 Participants	126 Participants	11 Participants
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 >=20%	115 Participants	111 Participants	7 Participants
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 >=30%	101 Participants	101 Participants	6 Participants
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 >=40%	90 Participants	90 Participants	6 Participants
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 >=50%	86 Participants	82 Participants	4 Participants
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 >=60%	78 Participants	70 Participants	4 Participants
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 >=70%	66 Participants	67 Participants	2 Participants
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 >=80%	55 Participants	57 Participants	2 Participants
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 >=90%	41 Participants	48 Participants	2 Participants

SECONDARY outcome

Timeframe: Weeks 5-24

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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.
Percentage of Participants Considered A Treatment Success	28.4 percentage of participants	29.1 percentage of participants	2.0 percentage of participants

SECONDARY outcome

Timeframe: Weekly from Weeks 5-24

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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.
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=0%	194 Participants	196 Participants	99 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=10%	140 Participants	129 Participants	17 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=20%	120 Participants	114 Participants	9 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=30%	106 Participants	109 Participants	8 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=40%	97 Participants	98 Participants	7 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=50%	91 Participants	88 Participants	6 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=60%	82 Participants	74 Participants	5 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=70%	73 Participants	69 Participants	4 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=80%	64 Participants	61 Participants	4 Participants
Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24 >=90%	47 Participants	51 Participants	2 Participants

SECONDARY outcome

Timeframe: Weekly from Weeks 5-24

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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.
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=0%	194 Participants	196 Participants	99 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=10%	163 Participants	162 Participants	37 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=20%	155 Participants	152 Participants	29 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=30%	139 Participants	139 Participants	24 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=40%	132 Participants	132 Participants	20 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=50%	125 Participants	125 Participants	18 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=60%	120 Participants	117 Participants	17 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=70%	108 Participants	112 Participants	14 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=80%	102 Participants	101 Participants	9 Participants
Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24 >=90%	92 Participants	91 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline: Day 1 (prior to dosing), Weeks 5-24

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

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=192 Participants 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.	RBP-6000 300mg/300mg n=193 Participants 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.	Combined Placebo n=96 Participants 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.
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	2.1 units on a scale Standard Error 1.63	-0.9 units on a scale Standard Error 1.63	11.5 units on a scale Standard Error 2.48

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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.
Participants Who Complete the Week 24 Visit ("Completers")	119 Participants	126 Participants	33 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set

Participants with both a negative urine sample and negative self-report for illicit opioid use at Week 24.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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.
Participants Who Are Abstinent at Week 24	71 Participants	87 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169

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

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=169 Participants 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.	RBP-6000 300mg/300mg n=173 Participants 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.	Combined Placebo n=60 Participants 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.
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	1.6 units on a scale Standard Error 0.11	1.5 units on a scale Standard Error 0.11	2.4 units on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169

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

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=166 Participants 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.	RBP-6000 300mg/300mg n=170 Participants 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.	Combined Placebo n=59 Participants 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.
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	-0.7 units on a scale Standard Error 0.13	-0.7 units on a scale Standard Error 0.13	-0.0 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=191 Participants 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.	RBP-6000 300mg/300mg n=192 Participants 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.	Combined Placebo n=96 Participants 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.
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures	-0.5 units on a scale Standard Error 0.22	-1.1 units on a scale Standard Error 0.21	-0.1 units on a scale Standard Error 0.35

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=192 Participants 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.	RBP-6000 300mg/300mg n=193 Participants 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.	Combined Placebo n=96 Participants 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.
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures	-0.9 units on a scale Standard Error 0.51	-2.0 units on a scale Standard Error 0.51	0.7 units on a scale Standard Error 0.80

SECONDARY outcome

Timeframe: Weeks 5 through 24

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=194 Participants 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.	RBP-6000 300mg/300mg n=196 Participants 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.	Combined Placebo n=99 Participants 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 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	8.5 weeks Standard Error 0.68	8.5 weeks Standard Error 0.68	1.0 weeks Standard Error 0.84

SECONDARY outcome

Timeframe: Day 1 through Week 24

Population: Safety analysis set

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=203 Participants 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.	RBP-6000 300mg/300mg n=201 Participants 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.	Combined Placebo n=100 Participants 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.
Participants With Adverse Events During the Treatment Period >=1 TEAE	155 Participants	134 Participants	56 Participants
Participants With Adverse Events During the Treatment Period >=1 TEAE related to study drug	67 Participants	70 Participants	23 Participants
Participants With Adverse Events During the Treatment Period >=1 serious TEAE	4 Participants	7 Participants	5 Participants
Participants With Adverse Events During the Treatment Period >=1 serious study treatment-related TEAE	0 Participants	0 Participants	0 Participants
Participants With Adverse Events During the Treatment Period Death	0 Participants	1 Participants	0 Participants
Participants With Adverse Events During the Treatment Period >=1 severe TEAE	15 Participants	13 Participants	4 Participants
Participants With Adverse Events During the Treatment Period TEAE leading to study treatment discontinuation	7 Participants	10 Participants	2 Participants

SECONDARY outcome

Timeframe: Days 1, 29, 57, 85, 113, 141

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=202 Participants 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.	RBP-6000 300mg/300mg n=201 Participants 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.	Combined Placebo n=100 Participants 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.
Worst Injection Site Pain From Injections 1-6 as Measured by Participant-Reported Visual Analog Scale (VAS)	55.8 units on a scale Standard Deviation 27.07	63.3 units on a scale Standard Deviation 29.33	61.0 units on a scale Standard Deviation 28.79

SECONDARY outcome

Timeframe: Weekly - Week 2 through Week 24

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

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.

Outcome measures

Outcome measures
Measure	RBP-6000 300mg/100mg n=202 Participants 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.	RBP-6000 300mg/300mg n=200 Participants 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.	Combined Placebo n=98 Participants 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.
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 Aborted attempt	1 Participants	1 Participants	1 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 Suicidal Ideation: Wish to be dead	15 Participants	11 Participants	9 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 Non-specific active suicidal thoughts	6 Participants	1 Participants	2 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 (subset of above) No plan nor intent to act	2 Participants	0 Participants	1 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 (subset of above) Non-specific plan, some intent	3 Participants	0 Participants	1 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 (subset of above) Specific plan and intent	0 Participants	0 Participants	0 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 Suicidal Behaviour: Preparatory acts or behaviour	0 Participants	0 Participants	0 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 Interrupted attempt	1 Participants	1 Participants	1 Participants
Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24 Actual attempt	0 Participants	0 Participants	0 Participants

Adverse Events

RBP-6000 300mg/100mg

Serious events: 4 serious events

Other events: 97 other events

Deaths: 0 deaths

RBP-6000 300mg/300mg

Serious events: 7 serious events

Other events: 84 other events

Deaths: 1 deaths

Combined Placebo

Serious events: 5 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RBP-6000 300mg/100mg n=203 participants at risk 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.	RBP-6000 300mg/300mg n=201 participants at risk 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.	Combined Placebo n=100 participants at risk 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.
Injury, poisoning and procedural complications Gun shot wound	0.00% 0/203 • Day 1 to Week 24	1.00% 2/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Asthma	0.49% 1/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.49% 1/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
General disorders Drug withdrawal syndrome	0.00% 0/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
General disorders Hernia	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Infections and infestations Abscess limb	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Infections and infestations Extradural abscess	0.00% 0/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
Cardiac disorders Acute myocardial infarction	0.49% 1/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Gastrointestinal disorders Food poisoning	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Hepatobiliary disorders Cholelithiasis	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.49% 1/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Nervous system disorders Myelomalacia	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Psychiatric disorders Suicidal ideation	0.00% 0/203 • Day 1 to Week 24	0.00% 0/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
Renal and urinary disorders Renal impairment	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Vascular disorders Hypotension	0.00% 0/203 • Day 1 to Week 24	0.50% 1/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24

Other adverse events

Other adverse events
Measure	RBP-6000 300mg/100mg n=203 participants at risk 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.	RBP-6000 300mg/300mg n=201 participants at risk 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.	Combined Placebo n=100 participants at risk 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.
Nervous system disorders Headache	9.4% 19/203 • Day 1 to Week 24	8.5% 17/201 • Day 1 to Week 24	6.0% 6/100 • Day 1 to Week 24
Gastrointestinal disorders Constipation	9.4% 19/203 • Day 1 to Week 24	8.0% 16/201 • Day 1 to Week 24	0.00% 0/100 • Day 1 to Week 24
Gastrointestinal disorders Nausea	8.9% 18/203 • Day 1 to Week 24	8.0% 16/201 • Day 1 to Week 24	5.0% 5/100 • Day 1 to Week 24
General disorders Injection site pruritus	6.4% 13/203 • Day 1 to Week 24	9.5% 19/201 • Day 1 to Week 24	4.0% 4/100 • Day 1 to Week 24
Gastrointestinal disorders Vomiting	9.4% 19/203 • Day 1 to Week 24	5.5% 11/201 • Day 1 to Week 24	4.0% 4/100 • Day 1 to Week 24
Psychiatric disorders Insomnia	6.4% 13/203 • Day 1 to Week 24	8.5% 17/201 • Day 1 to Week 24	11.0% 11/100 • Day 1 to Week 24
Infections and infestations Upper respiratory tract infection	7.4% 15/203 • Day 1 to Week 24	6.0% 12/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
General disorders Injection site pain	4.9% 10/203 • Day 1 to Week 24	6.0% 12/201 • Day 1 to Week 24	3.0% 3/100 • Day 1 to Week 24
Infections and infestations Nasopharyngitis	5.4% 11/203 • Day 1 to Week 24	5.0% 10/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24
General disorders Fatigue	3.9% 8/203 • Day 1 to Week 24	6.0% 12/201 • Day 1 to Week 24	3.0% 3/100 • Day 1 to Week 24
Investigations Blood creatine phosphokinase increased	5.4% 11/203 • Day 1 to Week 24	2.5% 5/201 • Day 1 to Week 24	1.0% 1/100 • Day 1 to Week 24

Additional Information

Global Director, Clinical Development

Indivior, Inc.

Phone: 804-379-1090

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER