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

NCT02357901 | Completed Phase 3 Results DMC

• 1 other identifier: RB-US-13-0001
• Study Type: interventional
• Target: 665
• Locations: 1 country
• Sites: 38

Brief Summary

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

Conditions

Opioid Dependence; Opioid Related Disorders

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Percentage of Participants Considered A Treatment Success

  Weeks 5-24

• Cumulative Distribution Function (CDF) of the Percentage of Urine Samples Negative for Opioids From Week 5 Through Week 24

  Weekly from Weeks 5-24

• Cumulative Distribution Function (CDF) of the Percentage of Self-Reports Negative for Illicit Opioid Use From Week 5 Through Week 24

  Weekly from Weeks 5-24

• Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) Prior to Injections From Week 5 Through Week 24 Analyzed by Mixed Model for Repeated Measures

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

• Participants Who Complete the Week 24 Visit ("Completers")

  Week 24

Study Arms (4)

RBP-6000 300mg/100mg

EXPERIMENTAL

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 are separated by 28 days (Day 57-Day 141) and contain RBP-6000 100 mg. In addition, participants received individual drug counseling (IDC) at least once a week.

Drug: SUBOXONE; Drug: RBP-6000

RBP-6000 300mg/300mg

EXPERIMENTAL

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days. In addition, participants received individual drug counseling (IDC) at least once a week.

Drug: SUBOXONE; Drug: RBP-6000

Placebo Matching 300 mg/100 mg RBP-6000

PLACEBO COMPARATOR

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given placebo injections on Days 1 and 29 (matching the RBP-6000 300 mg dose volume). Injections 3-6 are separated by 28 days (Day 57-Day 141) and also contain placebo (matching the RBP-6000 100 mg volume). In addition, participants received individual drug counseling (IDC) at least once a week.

Drug: SUBOXONE; Drug: Placebo

Placebo Matching 300 mg RBP-6000

PLACEBO COMPARATOR

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued. Participants in this treatment arm are given six placebo injections (volume-matched to RBP-6000 300 mg dose) on Days 1 to 141 with injections separated by 28 days. In addition, participants received individual drug counseling (IDC) at least once a week.

Drug: SUBOXONE; Drug: Placebo

Interventions

SUBOXONE DRUG

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.

Also known as: buprenorphine, Sublingual Film

Placebo Matching 300 mg RBP-6000; Placebo Matching 300 mg/100 mg RBP-6000; RBP-6000 300mg/100mg; RBP-6000 300mg/300mg

RBP-6000 DRUG

Six injections administered subcutaneously every 28 days on alternate sides of participant's abdomen at either 300 mg or 100 mg dose.

Also known as: Buprenorphine

RBP-6000 300mg/100mg; RBP-6000 300mg/300mg

Placebo DRUG

Six injections of placebo administered subcutaneously every 28 days on alternate sides of participant's abdomen at volumes matching the experimental drug.

Also known as: Volume-matched placebo

Placebo Matching 300 mg RBP-6000; Placebo Matching 300 mg/100 mg RBP-6000

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (38)

Haleyville Clinical Research

Haleyville, Alabama, 35565, United States

Location

Boyett Health Services

Hamilton, Alabama, 35570, United States

Location

Woodland International Research Group

Little Rock, Arkansas, 72211, United States

Location

Collaborative Neuroscience Network

Garden Grove, California, 92845, United States

Location

Behavioral Research Specialists

Glendale, California, 91206, United States

Location

Synergy Clinical Research Center

National City, California, 91950, United States

Location

North County Clinical Research

Oceanside, California, 92056, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Care Practice

San Francisco, California, 94103, United States

Location

Southern California Research

Thousand Oaks, California, 91360, United States

Location

Amit Vijapura

Jacksonville, Florida, 32256, United States

Location

Meridien Research

Lakeland, Florida, 38805, United States

Location

Innovative Clinical Research

Lauderhill, Florida, 33319, United States

Location

Florida Clinical Research Center

Maitland, Florida, 32751, United States

Location

Try Research

Maitland, Florida, 32751, United States

Location

Scientific Clinical Research

North Miami, Florida, 33161, United States

Location

Research Centers of America

Oakland Park, Florida, 33334, United States

Location

Behavioral Health Care Associates

Schaumburg, Illinois, 60194, United States

Location

Phoenix Medical Research

Prairie Village, Kansas, 66206, United States

Location

Louisiana Research Associates

New Orleans, Louisiana, 70114, United States

Location

Louisiana Clinical Research

Shreveport, Louisiana, 71101, United States

Location

Stanley Street Treatment and Resources

Fall River, Massachusetts, 02720, United States

Location

Adams Clinical Trials

Watertown, Massachusetts, 02472, United States

Location

Precise Research Centers, Inc.

Flowood, Mississippi, 39232, United States

Location

St Louis Clinical Trials

St Louis, Missouri, 63141, United States

Location

Altea Research

Las Vegas, Nevada, 89102, United States

Location

Comprehensive Clinical Research

Berlin, New Jersey, 08009, United States

Location

Neuro-behavioral Clinical Research

Canton, Ohio, 44718, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

Charak Clinical Research Center

Garfield Heights, Ohio, 44125, United States

Location

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, 73112, United States

Location

Pahl Pharmaceutical Professionals

Oklahoma City, Oklahoma, 73112, United States

Location

CODA

Portland, Oregon, 97214, United States

Location

Tipton Medical and Diagnostic Center aka Clinical Research Associates of Central PA

Altoona, Pennsylvania, 16602, United States

Location

UPenn Treatment Research Center

Philadelphia, Pennsylvania, 19104, United States

Location

Carolina Clinical Trials

Charleston, South Carolina, 29407, United States

Location

Pillar Clinical Research

Dallas, Texas, 75243, United States

Location

InSite Clinical Research

DeSoto, Texas, 75115, United States

Location

Related Publications (7)

• Greenwald MK, Wiest KL, Haight BR, Laffont CM, Zhao Y. Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder. Harm Reduct J. 2023 Dec 2;20(1):173. doi: 10.1186/s12954-023-00906-7.

  PMID: 38042801 DERIVED

• Rutrick D, Learned SM, Boyett B, Hassman D, Shinde S, Zhao Y. 18-Month efficacy and safety analysis of monthly subcutaneous buprenorphine injection for opioid use disorder: Integrated analysis of phase 3 studies. J Subst Use Addict Treat. 2023 Nov;154:209155. doi: 10.1016/j.josat.2023.209155. Epub 2023 Aug 30.

  PMID: 37657559 DERIVED

• Laffont CM, Ngaimisi E, Gopalakrishnan M, Ivaturi V, Young M, Greenwald MK, Heidbreder C. Buprenorphine exposure levels to optimize treatment outcomes in opioid use disorder. Front Pharmacol. 2022 Nov 18;13:1052113. doi: 10.3389/fphar.2022.1052113. eCollection 2022.

  PMID: 36467036 DERIVED

• Craft WH, Tegge AN, Keith DR, Shin H, Williams J, Athamneh LN, Stein JS, Chilcoat HD, Le Moigne A, DeVeaugh-Geiss A, Bickel WK. Recovery from opioid use disorder: A 4-year post-clinical trial outcomes study. Drug Alcohol Depend. 2022 May 1;234:109389. doi: 10.1016/j.drugalcdep.2022.109389. Epub 2022 Mar 9.

  PMID: 35287034 DERIVED

• Boyett B, Wiest K, McLeod LD, Nelson LM, Bickel WK, Learned SM, Heidbreder C, Fudala PJ, Le Moigne A, Zhao Y. Assessment of craving in opioid use disorder: Psychometric evaluation and predictive validity of the opioid craving VAS. Drug Alcohol Depend. 2021 Dec 1;229(Pt B):109057. doi: 10.1016/j.drugalcdep.2021.109057. Epub 2021 Sep 24.

  PMID: 34794061 DERIVED

• Kranzler HR, Lynch KG, Crist RC, Hartwell E, Le Moigne A, Laffont CM, Andorn AC. A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder. Int J Neuropsychopharmacol. 2021 Feb 15;24(2):89-96. doi: 10.1093/ijnp/pyaa069.

  PMID: 32920647 DERIVED

• Haight BR, Learned SM, Laffont CM, Fudala PJ, Zhao Y, Garofalo AS, Greenwald MK, Nadipelli VR, Ling W, Heidbreder C; RB-US-13-0001 Study Investigators. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2019 Feb 23;393(10173):778-790. doi: 10.1016/S0140-6736(18)32259-1. Epub 2019 Feb 18.

  PMID: 30792007 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination; Buprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Global Director, Clinical Development
• Organization: Indivior, Inc.

804-379-1090

Study Officials

• Director Global Clinical Development

  Indivior Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 6, 2015
• Study Start: January 28, 2015
• Primary Completion: April 29, 2016
• Study Completion: April 29, 2016
• Last Updated: February 20, 2018
• Results First Posted: February 20, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (38)