Safety and Tolerability Study of Depot Buprenorphine in Treatment Seeking Subjects With Opioid Use Disorder

NCT02510014 | Completed Phase 3 Results

• 1 other identifier: RB-US-13-0003
• Study Type: interventional
• Target: 775
• Locations: 1 country
• Sites: 42

Brief Summary

A multi-center, open-label, long-term safety study in which approximately 600 subjects diagnosed with opioid use disorder will be enrolled. Following a screening period, all subjects will receive run in SUBOXONE sublingual film followed by an initial injection of open-label high dose (300 mg) RBP-6000. The RBP-6000 monthly injection dose can be adjusted to low dose (100 mg), and back to high dose, based on the medical judgment of the Investigator. Subjects will participate in the study for either 6 or 12 months.

Conditions

Opioid Use Disorder; Opioid-related Disorders

Outcome Measures

Primary Outcomes (4)

• Participants With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period

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

• Percentage Change From Baseline to End of Study (Weeks 25 and 49) in Vital Signs

  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.

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

• Shifts in Suicidality Using the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Most Severe Assessment 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. 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'.

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

• Worst Local Injection Site Pain From Injections 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' 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.

  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

Secondary Outcomes (4)

• Change From Baseline in the Clinical Opiate Withdrawal Scale (COWS) at End of Study (Weeks 25 and 49)

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

• Change From Baseline in the Subjective Opiate Withdrawal Scale (SOWS) at End of Study (Weeks 25 and 49)

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

• Change From Baseline in the Opioid Craving Visual Analog Scale (VAS) at End of Study (Weeks 25 and 49)

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

• Cumulative Distribution Function (CDF) of the Percentage Abstinence Collected From Week 1 Through End of Study (Weeks 25 and 49)

  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

Study Arms (2)

Roll-over Subjects

EXPERIMENTAL

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.

Drug: SUBOXONE sublingual film; Drug: RBP-6000

De Novo Subjects

EXPERIMENTAL

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.

Drug: SUBOXONE sublingual film; Drug: RBP-6000

Interventions

SUBOXONE sublingual film DRUG

SUBOXONE (buprenorphine sublingual film) is used for induction therapy on Days -14 to -12. Participants then complete a 4-to-11 day sublingual film dose adjustment at doses ranging from 8 mg to 24 mg sublingual film prior to starting the Treatment Period.

Also known as: SUBOXONE, buprenorphine

De Novo Subjects; Roll-over Subjects

RBP-6000 DRUG

Injections administered subcutaneously every 28 days on alternate sides of participant's abdomen starting at 300 mg. Subsequent doses of RBP-6000 could be adjusted down to 100 mg with the possibility of adjusting back up to 300 mg based on the medical judgment of the investigator. De novo subjects receive up to 12 injections and roll-over subjects receive up to 6 injections.

Also known as: Atrigel buprenorphine

De Novo Subjects; Roll-over Subjects

Eligibility Criteria

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

You may qualify if:

• De novo subjects:
• Seeking treatment for opioid use disorder (OUD) and for the previous 3 months meet the Diagnostic and Statistical Manual 5 (DSM-5) criteria for moderate or severe OUD
• Appropriate candidate for opioid partial-agonist treatment
• BMI between 18 and 35, inclusive
• Roll-over subjects:
• Completed RB-US-13-0001

You may not qualify if:

• De novo subjects:
• Current diagnosis, other than OUD, requiring chronic opioid treatment
• Current substance use disorder with regard to substances other than opioids, cocaine, cannabis, tobacco or alcohol
• Received medication-assisted treatment for OUD in the 90 days prior to informed consent
• Use (within past 30 days prior to informed consent) or positive urine drug screen (UDS) at screening for barbiturates, benzodiazepines,methadone or buprenorphine
• Treatment for OUD required by court order
• History of recent suicidal ideation or attempt
• Roll over subjects:
• Experienced major protocol deviations or adverse events in RB-US-13-0001 which could potentially compromise subject safety
• Discontinued early from study RB-US-13-0001

Sponsors & Collaborators

• Indivior Inc.: lead

Study Sites (42)

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

Pacific Research Partners

Oakland, California, 94612, United States

Location

North County Clinical Research

Oceanside, California, 92056, United States

Location

Neuropsychiatric Research Center of Orange County

Orange, California, 92868, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Amit Vijapura

Jacksonville, Florida, 32256, United States

Location

Sarkis Clinical Trials

Lake City, Florida, 32025, United States

Location

Meridien Research

Lakeland, Florida, 33805, 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

Atlanta Institute of Medicine and Research

Alpharetta, Georgia, 30005, 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

Center for Emotional Fitness

Cherry Hill, New Jersey, 08002, United States

Location

The Medical Research Network, LLC

New York, New York, 10128, 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

Aspen Clinical Research, LLC

Orem, Utah, 84058, United States

Location

Related Publications (2)

• 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

• 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

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.

Robert.Bauer@Indivior.com

804-379-1090

Study Officials

• Global Director 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: July 28, 2015
• Study Start: July 27, 2015
• Primary Completion: January 31, 2017
• Study Completion: January 31, 2017
• Last Updated: March 29, 2018
• Results First Posted: March 29, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (42)