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

Opioid Dependence Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Assess the Efficacy, Safety, and Tolerability of Multiple Subcutaneous Injections of Depot Buprenorphine (RBP-6000 [100 mg and 300 mg]) Over 24 Weeks in Treatment-Seeking Subjects With Opioid Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02357901
• Other study ID #: RB-US-13-0001
• Status: Completed
• Phase: Phase 3
• First received: February 3, 2015
• Last updated: February 16, 2018
• Start date: January 28, 2015
• Est. completion date: April 29, 2016

Study information

• Verified date: February 2018
• Source: Indivior Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 665
• Est. completion date: April 29, 2016
• Est. primary completion date: April 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder

• By medical history has met DSM-5 criteria for moderate or severe opioid use disorder for the 3 months immediately prior to signing the informed consent form

• Is seeking medication-assisted treatment for opioid use disorder

• Is an appropriate candidate for opioid partial-agonist medication-assisted treatment in the opinion of the investigator or medically responsible physician

• Body mass index (BMI) of = 18.0 to = 35.0 kg/m^2

Exclusion Criteria:

• Current diagnosis other than opioid use disorder requiring chronic opioid treatment

• Current substance use disorder as defined by DSM-5 criteria with regard to any substances other than opioids, cocaine, cannabis, tobacco, or alcohol.

• Positive urine drug screen (UDS) result at screening for cocaine or cannabis AND meets DSM-5 criteria for either moderate or severe cocaine or cannabis use disorder, respectively

• Meets DSM-5 criteria for moderate or severe alcohol use disorder

• Received medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine) in the 90 days prior to providing written informed consent

Related Conditions & MeSH terms

• Disease
• Opioid Dependence
• Opioid Related Disorders
• Opioid-Related Disorders

Intervention

Drug:
• SUBOXONE
SUBOXONE (buprenorphine sublingual film) is used for induction therapy. Participants take sublingual film for 3 days according to the sublingual film prescribing information; they then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to randomization. Following randomization, SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.
• RBP-6000
Six injections administered subcutaneously every 28 days on alternate sides of participant's abdomen at either 300 mg or 100 mg dose.
• Placebo
Six injections of placebo administered subcutaneously every 28 days on alternate sides of participant's abdomen at volumes matching the experimental drug.

Locations

Country	Name	City	State
United States	Tipton Medical and Diagnostic Center aka Clinical Research Associates of Central PA	Altoona	Pennsylvania
United States	Comprehensive Clinical Research	Berlin	New Jersey
United States	Neuro-behavioral Clinical Research	Canton	Ohio
United States	Carolina Clinical Trials	Charleston	South Carolina
United States	Pillar Clinical Research	Dallas	Texas
United States	Midwest Clinical Research Center	Dayton	Ohio
United States	InSite Clinical Research	DeSoto	Texas
United States	Stanley Street Treatment and Resources	Fall River	Massachusetts
United States	Precise Research Centers, Inc.	Flowood	Mississippi
United States	Collaborative Neuroscience Network	Garden Grove	California
United States	Charak Clinical Research Center	Garfield Heights	Ohio
United States	Behavioral Research Specialists	Glendale	California
United States	Haleyville Clinical Research	Haleyville	Alabama
United States	Boyett Health Services	Hamilton	Alabama
United States	Amit Vijapura	Jacksonville	Florida
United States	Meridien Research	Lakeland	Florida
United States	Altea Research	Las Vegas	Nevada
United States	Innovative Clinical Research	Lauderhill	Florida
United States	Woodland International Research Group	Little Rock	Arkansas
United States	Florida Clinical Research Center	Maitland	Florida
United States	Try Research	Maitland	Florida
United States	Synergy Clinical Research Center	National City	California
United States	Louisiana Research Associates	New Orleans	Louisiana
United States	Scientific Clinical Research	North Miami	Florida
United States	Research Centers of America	Oakland Park	Florida
United States	North County Clinical Research	Oceanside	California
United States	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma
United States	Pahl Pharmaceutical Professionals	Oklahoma City	Oklahoma
United States	UPenn Treatment Research Center	Philadelphia	Pennsylvania
United States	CODA	Portland	Oregon
United States	Phoenix Medical Research	Prairie Village	Kansas
United States	St Louis Clinical Trials	Saint Louis	Missouri
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Care Practice	San Francisco	California
United States	Behavioral Health Care Associates	Schaumburg	Illinois
United States	Louisiana Clinical Research	Shreveport	Louisiana
United States	Southern California Research	Thousand Oaks	California
United States	Adams Clinical Trials	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Indivior Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Weekly from Weeks 5-24
Secondary	Percentage of Participants Considered A Treatment Success	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.	Weeks 5-24
Secondary	Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24	Data represent the count of participants at various percentage levels in which urine samples tested negative for opioids. All missing reports for urine samples were considered non-negative.	Weekly from Weeks 5-24
Secondary	Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24	Data represent the count of participants at various percentage levels in which self-reports were negative for illicit use of opioids. Self-reports were obtained from Timeline Followback (TLFB) interviews. All missing self-reports were considered non-negative.	Weekly from Weeks 5-24
Secondary	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	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.	Baseline: Day 1 (prior to dosing), Weeks 5-24
Secondary	Participants Who Complete the Week 24 Visit ("Completers")	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.	Week 24
Secondary	Participants Who Are Abstinent at Week 24	Participants with both a negative urine sample and negative self-report for illicit opioid use at Week 24.	Week 24
Secondary	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	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.	Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169
Secondary	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	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.	Baseline: Day 1 (prior to dosing), Days 29, 57, 85, 113, 141, 169
Secondary	Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures	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.	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
Secondary	Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) Through Week 24 Analyzed by Mixed Model for Repeated Measures	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.	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
Secondary	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	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.	Weeks 5 through 24
Secondary	Participants With Adverse Events During the Treatment Period	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.	Day 1 through Week 24
Secondary	Worst Injection Site Pain From Injections 1-6 as Measured by Participant-Reported Visual Analog Scale (VAS)	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.	Days 1, 29, 57, 85, 113, 141
Secondary	Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Week 2 - 24	The C-SSRS asks questions of study participants regarding whether they had suicidal ideation and/or suicidal behavior since the last visit using the electronic version of the scale. The C-SSRS was completed each week; measurements were taken prior to dosing on weeks 5, 9, 13, 17 and 21.	Weekly - Week 2 through Week 24