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

NCT ID: NCT02357901

Last Updated: 2018-02-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

665 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-28

Study Completion Date

2016-04-29

Brief Summary

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

Detailed Description

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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.

Conditions

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Opioid Dependence Opioid Related Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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RBP-6000 300mg/100mg

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.

Participants in this treatment arm are given RBP-6000 300 mg injections on Days 1 and 29. Injections 3-6 are separated by 28 days (Day 57-Day 141) and contain RBP-6000 100 mg.

In addition, participants received individual drug counseling (IDC) at least once a week.

Group Type EXPERIMENTAL

SUBOXONE

Intervention Type 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.

RBP-6000

Intervention Type DRUG

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

RBP-6000 300mg/300mg

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.

Participants in this treatment arm are given six RBP-6000 300 mg injections on Days 1 to 141 with injections separated by 28 days.

In addition, participants received individual drug counseling (IDC) at least once a week.

Group Type EXPERIMENTAL

SUBOXONE

Intervention Type 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.

RBP-6000

Intervention Type DRUG

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

Placebo Matching 300 mg/100 mg RBP-6000

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.

Participants in this treatment arm are given placebo injections on Days 1 and 29 (matching the RBP-6000 300 mg dose volume). Injections 3-6 are separated by 28 days (Day 57-Day 141) and also contain placebo (matching the RBP-6000 100 mg volume).

In addition, participants received individual drug counseling (IDC) at least once a week.

Group Type PLACEBO_COMPARATOR

SUBOXONE

Intervention Type 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.

Placebo

Intervention Type DRUG

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

Placebo Matching 300 mg RBP-6000

During the Run-In Period, participants are inducted onto SUBOXONE sublingual film (SL) followed by a 4- to 11-day SUBOXONE sublingual film open-label run-in dose-adjustment period to achieve buprenorphine dosages ranging from 8 to 24 mg according to the SUBOXONE sublingual film prescribing information. Participants are then randomized. As of protocol Amendment 2 (21 August 2015) SUBOXONE use is tapered from 6 mg to 2 mg from Days 1-5 and then discontinued.

Participants in this treatment arm are given six placebo injections (volume-matched to RBP-6000 300 mg dose) on Days 1 to 141 with injections separated by 28 days.

In addition, participants received individual drug counseling (IDC) at least once a week.

Group Type PLACEBO_COMPARATOR

SUBOXONE

Intervention Type 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.

Placebo

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DRUG

RBP-6000

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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buprenorphine Sublingual Film Buprenorphine Volume-matched placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Indivior Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Director Global Clinical Development

Role: STUDY_DIRECTOR

Indivior Inc.

Locations

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Haleyville Clinical Research

Haleyville, Alabama, United States

Site Status

Boyett Health Services

Hamilton, Alabama, United States

Site Status

Woodland International Research Group

Little Rock, Arkansas, United States

Site Status

Collaborative Neuroscience Network

Garden Grove, California, United States

Site Status

Behavioral Research Specialists

Glendale, California, United States

Site Status

Synergy Clinical Research Center

National City, California, United States

Site Status

North County Clinical Research

Oceanside, California, United States

Site Status

Artemis Institute for Clinical Research

San Diego, California, United States

Site Status

Care Practice

San Francisco, California, United States

Site Status

Southern California Research

Thousand Oaks, California, United States

Site Status

Amit Vijapura

Jacksonville, Florida, United States

Site Status

Meridien Research

Lakeland, Florida, United States

Site Status

Innovative Clinical Research

Lauderhill, Florida, United States

Site Status

Florida Clinical Research Center

Maitland, Florida, United States

Site Status

Try Research

Maitland, Florida, United States

Site Status

Scientific Clinical Research

North Miami, Florida, United States

Site Status

Research Centers of America

Oakland Park, Florida, United States

Site Status

Behavioral Health Care Associates

Schaumburg, Illinois, United States

Site Status

Phoenix Medical Research

Prairie Village, Kansas, United States

Site Status

Louisiana Research Associates

New Orleans, Louisiana, United States

Site Status

Louisiana Clinical Research

Shreveport, Louisiana, United States

Site Status

Stanley Street Treatment and Resources

Fall River, Massachusetts, United States

Site Status

Adams Clinical Trials

Watertown, Massachusetts, United States

Site Status

Precise Research Centers, Inc.

Flowood, Mississippi, United States

Site Status

St Louis Clinical Trials

St Louis, Missouri, United States

Site Status

Altea Research

Las Vegas, Nevada, United States

Site Status

Comprehensive Clinical Research

Berlin, New Jersey, United States

Site Status

Neuro-behavioral Clinical Research

Canton, Ohio, United States

Site Status

Midwest Clinical Research Center

Dayton, Ohio, United States

Site Status

Charak Clinical Research Center

Garfield Heights, Ohio, United States

Site Status

Oklahoma Clinical Research Center

Oklahoma City, Oklahoma, United States

Site Status

Pahl Pharmaceutical Professionals

Oklahoma City, Oklahoma, United States

Site Status

CODA

Portland, Oregon, United States

Site Status

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

Altoona, Pennsylvania, United States

Site Status

UPenn Treatment Research Center

Philadelphia, Pennsylvania, United States

Site Status

Carolina Clinical Trials

Charleston, South Carolina, United States

Site Status

Pillar Clinical Research

Dallas, Texas, United States

Site Status

InSite Clinical Research

DeSoto, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 38042801 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37657559 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36467036 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35287034 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34794061 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32920647 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30792007 (View on PubMed)

Other Identifiers

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RB-US-13-0001

Identifier Type: -

Identifier Source: org_study_id

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