Trial Outcomes & Findings for Safety and Tolerability Study of Depot Buprenorphine in Treatment Seeking Subjects With Opioid Use Disorder (NCT NCT02510014)

Last Updated: 2018-03-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

775 participants

Primary outcome timeframe

Day 1 to Week 49 (De novo arm); Day 1 to Week 25 (Roll-over arm)

Results posted on

2018-03-29

Participant Flow

A total of 994 subjects were screened by 39 sites, and of those, 775 subjects entered the run-in period receiving at least 1 dose of SUBOXONE (508 de novo subjects and 267 roll-over subjects).

Participant milestones

Participant milestones
Measure	De Novo Subjects Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Run-In Period (Days -14 to Day -1) STARTED	508	267
Run-In Period (Days -14 to Day -1) COMPLETED	412	257
Run-In Period (Days -14 to Day -1) NOT COMPLETED	96	10
Treatment Period STARTED	412	257
Treatment Period COMPLETED	206	200
Treatment Period NOT COMPLETED	206	57

Reasons for withdrawal

Reasons for withdrawal
Measure	De Novo Subjects Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Run-In Period (Days -14 to Day -1) Adverse Event	1	1
Run-In Period (Days -14 to Day -1) Withdrawal symptoms	1	0
Run-In Period (Days -14 to Day -1) Lost to Follow-up	44	3
Run-In Period (Days -14 to Day -1) Physician Decision	0	1
Run-In Period (Days -14 to Day -1) Withdrawal by Subject	22	3
Run-In Period (Days -14 to Day -1) Withdrawn by the investigator	7	1
Run-In Period (Days -14 to Day -1) Protocol Violation	2	0
Run-In Period (Days -14 to Day -1) Other	19	1
Treatment Period Adverse Event	11	4
Treatment Period Withdrawal symptoms	3	0
Treatment Period Lost to Follow-up	80	19
Treatment Period Physician Decision	5	0
Treatment Period Withdrawal by Subject	67	24
Treatment Period Withdrawn by the investigator	7	1
Treatment Period Protocol Violation	4	4
Treatment Period Incarceration, pregnancy, misc	29	5

Baseline Characteristics

Records for one participant were missing baseline waist-to-hip ratio.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.	Total n=669 Participants Total of all reporting groups
Age, Continuous	38.4 years STANDARD_DEVIATION 12.10 • n=412 Participants	41.6 years STANDARD_DEVIATION 11.07 • n=257 Participants	39.6 years STANDARD_DEVIATION 11.81 • n=669 Participants
Age, Customized >=18 to <30 years	122 Participants n=412 Participants	40 Participants n=257 Participants	162 Participants n=669 Participants
Age, Customized >=30 to <45 years	157 Participants n=412 Participants	114 Participants n=257 Participants	271 Participants n=669 Participants
Age, Customized >=45 to <60 years	107 Participants n=412 Participants	89 Participants n=257 Participants	196 Participants n=669 Participants
Age, Customized >= 60 to < 65 years	25 Participants n=412 Participants	14 Participants n=257 Participants	39 Participants n=669 Participants
Age, Customized >=65 years	1 Participants n=412 Participants	0 Participants n=257 Participants	1 Participants n=669 Participants
Sex: Female, Male Female	149 Participants n=412 Participants	88 Participants n=257 Participants	237 Participants n=669 Participants
Sex: Female, Male Male	263 Participants n=412 Participants	169 Participants n=257 Participants	432 Participants n=669 Participants
Race/Ethnicity, Customized Hispanic or Latino	43 Participants n=412 Participants	16 Participants n=257 Participants	59 Participants n=669 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	369 Participants n=412 Participants	241 Participants n=257 Participants	610 Participants n=669 Participants
Race White	295 Participants n=412 Participants	167 Participants n=257 Participants	462 Participants n=669 Participants
Race Black or African American	107 Participants n=412 Participants	85 Participants n=257 Participants	192 Participants n=669 Participants
Race Native Hawaiian or Other Pacific Islander	0 Participants n=412 Participants	1 Participants n=257 Participants	1 Participants n=669 Participants
Race American Indian or Alaska Native	2 Participants n=412 Participants	2 Participants n=257 Participants	4 Participants n=669 Participants
Race Asian	2 Participants n=412 Participants	0 Participants n=257 Participants	2 Participants n=669 Participants
Race Multiple	2 Participants n=412 Participants	2 Participants n=257 Participants	4 Participants n=669 Participants
Race Other	4 Participants n=412 Participants	0 Participants n=257 Participants	4 Participants n=669 Participants
Weight	75.49 kg STANDARD_DEVIATION 14.658 • n=412 Participants	78.43 kg STANDARD_DEVIATION 18.097 • n=257 Participants	76.62 kg STANDARD_DEVIATION 16.117 • n=669 Participants
Waist-to-Hip Ratio	0.91 ratio STANDARD_DEVIATION 0.086 • n=411 Participants • Records for one participant were missing baseline waist-to-hip ratio.	0.90 ratio STANDARD_DEVIATION 0.083 • n=257 Participants • Records for one participant were missing baseline waist-to-hip ratio.	0.90 ratio STANDARD_DEVIATION 0.085 • n=668 Participants • Records for one participant were missing baseline waist-to-hip ratio.
Body Mass Index	25.38 kg/m^2 STANDARD_DEVIATION 4.286 • n=412 Participants	26.14 kg/m^2 STANDARD_DEVIATION 5.067 • n=257 Participants	25.67 kg/m^2 STANDARD_DEVIATION 4.613 • n=669 Participants
Tobacco use Never	40 Participants n=412 Participants	23 Participants n=257 Participants	63 Participants n=669 Participants
Tobacco use Former	18 Participants n=412 Participants	12 Participants n=257 Participants	30 Participants n=669 Participants
Tobacco use Current	354 Participants n=412 Participants	222 Participants n=257 Participants	576 Participants n=669 Participants
Caffeine use Never	33 Participants n=412 Participants	21 Participants n=257 Participants	54 Participants n=669 Participants
Caffeine use Former	13 Participants n=412 Participants	7 Participants n=257 Participants	20 Participants n=669 Participants
Caffeine use Current	365 Participants n=412 Participants	229 Participants n=257 Participants	594 Participants n=669 Participants
Caffeine use Missing data	1 Participants n=412 Participants	0 Participants n=257 Participants	1 Participants n=669 Participants
Alcohol use Never	122 Participants n=412 Participants	48 Participants n=257 Participants	170 Participants n=669 Participants
Alcohol use Former	97 Participants n=412 Participants	65 Participants n=257 Participants	162 Participants n=669 Participants
Alcohol use Current	193 Participants n=412 Participants	144 Participants n=257 Participants	337 Participants n=669 Participants

PRIMARY outcome

Timeframe: Day 1 to Week 49 (De novo arm); Day 1 to Week 25 (Roll-over arm)

Population: Safety analysis set

Outcome measures

Outcome measures
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period >=1 TEAE	302 Participants	145 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period >=1 TEAE related to study drug	172 Participants	61 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period >=1 serious TEAE	16 Participants	9 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period >=1 serious study treatment-related TEAE	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period Death	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period >=1 severe TEAE	36 Participants	7 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period TEAE leading to study treatment discontinuation	13 Participants	4 Participants
Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period TEAE leading to dose reduction	29 Participants	17 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 predose) End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Population: Safety analysis set of participants with both a baseline and end of study reading

Vital signs include * systolic blood pressure (mmHg) * diastolic blood pressure (mmHg) * respiratory rate (breaths/minute) * weight (kg) * body mass index (kg/m\^2) * waist-to-hip ratio Baseline is defined as the last non-missing value prior to subcutaneous injection of RBP-6000 on Day 1.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=206 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=198 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs Systolic blood pressure	0.2 percentage change from baseline Standard Deviation 11.69	1.3 percentage change from baseline Standard Deviation 11.25
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs Waist-to-hip ratio	1.828 percentage change from baseline Standard Deviation 11.1698	1.015 percentage change from baseline Standard Deviation 8.1150
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs Diastolic blood pressure	0.1 percentage change from baseline Standard Deviation 13.97	1.6 percentage change from baseline Standard Deviation 12.49
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs Respiratory rate	-1.2 percentage change from baseline Standard Deviation 11.11	1.0 percentage change from baseline Standard Deviation 11.02
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs Body weight	1.52 percentage change from baseline Standard Deviation 10.651	-0.94 percentage change from baseline Standard Deviation 6.497
Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs Body mass index	1.53 percentage change from baseline Standard Deviation 10.657	-0.93 percentage change from baseline Standard Deviation 6.507

PRIMARY outcome

Timeframe: Baseline (Screening visit, days -21 to -15), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Population: Safety population. Four de novo subjects and one roll-over subject are not reported because they used the C-SSRS baseline version throughout the study.

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. Only the most severe assessment is reported in this summary. Participants who experienced suicidal ideation and suicidal behavior are only summarized in the suicidal behavior since behavior is more severe than ideation. C-SSRS baseline version was completed during the screening visit. C-SSRS 'since-last-visit' version was completed weekly for the first month and at least every month until the end of the study. Shift table category titles are structured as: baseline category/treatment category. The category 'No Suicidal Ideation or Behaviour' has been abbreviated as 'No Suicidal I or B'.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=408 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=256 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period No Suicidal I or B / No Suicidal I or B	307 Participants	252 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period No Suicidal I or B / Suicidal Ideation	10 Participants	1 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period Suicidal Ideation / No Suicidal I or B	46 Participants	1 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period Suicidal Ideation / Suicidal Behaviour	3 Participants	0 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period Suicidal Behaviour / Suicidal Ideation	2 Participants	0 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period Suicidal Behaviour / Suicidal Behaviour	2 Participants	0 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period No Suicidal I or B / Suicidal Behaviour	3 Participants	1 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period Suicidal Ideation / Suicidal Ideation	7 Participants	1 Participants
Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment During the Treatment Period Suicidal Behaviour / No Suicidal I or B	28 Participants	0 Participants

PRIMARY outcome

Timeframe: De Novo Subjects: Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309 Roll-over Subjects: Days 1, 29, 57, 85, 113, 141

Population: Safety analysis set

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' at 0 mm and 'strongest pain ever' at 100 mm (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 and 60 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 injections and all VAS records. The mean value is presented. De Novo subjects were given injections on Days 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281 and 309. Roll-over subjects were given injections on Days 1, 29, 57, 85, 113, 141.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 1	44.0 units on a scale Standard Deviation 29.86	33.5 units on a scale Standard Deviation 31.50
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 3	38.9 units on a scale Standard Deviation 32.14	30.2 units on a scale Standard Deviation 32.09
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 4	33.6 units on a scale Standard Deviation 32.86	31.3 units on a scale Standard Deviation 31.72
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 5	30.6 units on a scale Standard Deviation 30.96	32.2 units on a scale Standard Deviation 31.25
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 6	30.5 units on a scale Standard Deviation 31.89	30.5 units on a scale Standard Deviation 30.88
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 7	28.9 units on a scale Standard Deviation 32.13	—
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 8	28.6 units on a scale Standard Deviation 30.21	—
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 9	30.2 units on a scale Standard Deviation 33.96	—
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 10	31.8 units on a scale Standard Deviation 33.16	—
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 11	25.8 units on a scale Standard Deviation 30.71	—
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 12	24.7 units on a scale Standard Deviation 28.22	—
Worst Local Injection Site Pain From Injections as Measured by Participant-Reported Visual Analog Scale (VAS) Injection 2	39.8 units on a scale Standard Deviation 31.98	32.7 units on a scale Standard Deviation 31.59

SECONDARY outcome

Timeframe: Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Population: Safety analysis set

COWS is an 11-item instrument used to assess signs and symptoms of opioid withdrawal. 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. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) Change from baseline: Week 49	-1.0 units on a scale Standard Deviation 2.41	—
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) Baseline (actual value)	2.1 units on a scale Standard Deviation 2.43	1.5 units on a scale Standard Deviation 1.98
Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49) Change from baseline: Week 25	-1.0 units on a scale Standard Deviation 2.61	-0.3 units on a scale Standard Deviation 2.37

SECONDARY outcome

Timeframe: Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Population: Safety analysis set

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. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) Baseline (actual value)	3.8 units on a scale Standard Deviation 5.27	2.8 units on a scale Standard Deviation 5.44
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) Change from baseline: Week 25	-1.1 units on a scale Standard Deviation 6.63	1.1 units on a scale Standard Deviation 7.17
Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49) Change from baseline: Week 49	-1.6 units on a scale Standard Deviation 5.05	—

SECONDARY outcome

Timeframe: Baseline (Day 1 predose), End of Study: Week 49 (De novo arm); Week 25 (Roll-over arm)

Population: Safety analysis set

The opioid craving scale was a 100 mm scale with 'no craving' indicated by 0 mm and 'strongest craving ever' indicated by 100 mm. Participants marked where along the scale reflected their craving for opioids. Baseline was defined as the last non-missing value prior to subcutaneous injection on Day 1. Baseline value is reported as an observed actual value. Weeks 25 and 49 represent change from baseline values.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) Baseline (actual value)	5.9 units on a scale Standard Deviation 10.59	4.4 units on a scale Standard Deviation 9.62
Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) Change from baseline: Week 25	-0.2 units on a scale Standard Deviation 16.19	4.2 units on a scale Standard Deviation 16.77
Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49) Change from baseline: Week 49	-2.0 units on a scale Standard Deviation 10.83	—

SECONDARY outcome

Timeframe: Weekly during Month 1, Every other week from Month 2-6, Monthly from Month 7-12. De novo arm stopped at Week 49. Roll-over arm stopped at Week 25

Population: Safety analysis set

Participants' self-reported illicit opioid drug use from the timeline followback (TLFB) interview and results from the urine drug screens (UDS) for opioids were combined into a single endpoint. Opioids assessed included codeine, hydrocodone, hydromorphone, methadone, morphine, opiates, oxycodone, and oxymorphone (by UDS) and amphetamine/methadone, buprenorphine, methadone, and opioids in the TLFB. 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 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. All missing reports for opioids were considered nonnegative.

Outcome measures

Outcome measures
Measure	De Novo Subjects n=412 Participants Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 Participants Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=10%	315 Participants	206 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=20%	278 Participants	200 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=70%	132 Participants	110 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=0%	412 Participants	257 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=30%	239 Participants	189 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=40%	217 Participants	159 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=50%	187 Participants	150 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=60%	166 Participants	137 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=80%	98 Participants	96 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) >=90%	62 Participants	74 Participants
Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49) =100%	32 Participants	47 Participants

Adverse Events

De Novo Subjects

Serious events: 16 serious events

Other events: 146 other events

Deaths: 0 deaths

Roll-over Subjects

Serious events: 9 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	De Novo Subjects n=412 participants at risk Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 participants at risk Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Gastrointestinal disorders Constipation	11.4% 47/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	3.5% 9/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Gastrointestinal disorders Nausea	9.0% 37/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	3.9% 10/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
General disorders Injection site pain	9.5% 39/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	2.7% 7/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Psychiatric disorders Insomnia	6.6% 27/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	3.9% 10/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Nervous system disorders Headache	7.5% 31/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	1.9% 5/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Nasopharyngitis	5.8% 24/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	2.3% 6/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
General disorders Injection site erythema	5.3% 22/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	1.9% 5/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm

Additional Information

Global Director, Clinical Development

Indivior, Inc.

Phone: 804-379-1090

Email: [email protected]

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

Measure	De Novo Subjects n=412 participants at risk Subjects who did not participate in RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 12 months in the Treatment period.	Roll-over Subjects n=257 participants at risk Subjects who completed RB-US-13-0001 received SUBOXONE sublingual film during the Run-In period, followed by an initial open-label injection of 300 mg RBP-6000. Participants continued with monthly injections of either 300 mg or 100 mg (based on judgement of the Investigator) for a total of 6 months in the Treatment period.
Infections and infestations Cellulitis	0.49% 2/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Abscess limb	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Appendicitis	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Escherichia pyelonephritis	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Localised infection	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Pneumonia viral	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Prostatic abscess	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Staphylococcal bacteraemia	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Infections and infestations Urinary tract infection	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Injury, poisoning and procedural complications Accidental overdose	0.49% 2/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Injury, poisoning and procedural complications Arthropod bite	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Injury, poisoning and procedural complications Laceration	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Injury, poisoning and procedural complications Multiple fractures	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Injury, poisoning and procedural complications Road traffic accident	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Injury, poisoning and procedural complications Thermal burn	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Psychiatric disorders Adjustment disorder with mixed anxiety and depressed mood	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Psychiatric disorders Major depression	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Psychiatric disorders Mania	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Respiratory, thoracic and mediastinal disorders Asthma	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Nervous system disorders Dizziness	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Cardiac disorders Myocardial infarction	0.00% 0/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.39% 1/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Gastrointestinal disorders Abdominal pain	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Hepatobiliary disorders Gallbladder perforation	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Metabolism and nutrition disorders Hypokalaemia	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm
Vascular disorders Thrombophlebitis superficial	0.24% 1/412 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm	0.00% 0/257 • Day 1 to Week 49 for De Novo arm Day 1 to Week 25 for the Roll-over arm