Clinical trial NCT04995029: Buprenorphine Extended-Release Subcutaneous Injection (RBP-6000) in High-risk Users
Official title: A Randomised, Double-Blind Study Comparing 2 Maintenance Dosing Regimens of Buprenorphine Extended-Release Subcutaneous Injection (RBP-6000) in Treatment-Seeking Adult Participants with Opioid Use Disorder and High-risk Opioid Use
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Moderate to Severe Opioid-use Disorder
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 785
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the induction phase of the study is to compare treatment retention of participants following rapid induction or standard of care (SoC) induction onto extended-release buprenorphine.

The primary objective of the maintenance phase is to compare the efficacy of 100 mg and 300 mg maintenance doses of extended-release buprenorphine administered every 4 weeks.

Detailed description: This study consists of an open-label induction phase followed by a double-blind maintenance phase. Each phase is designed to test separate objectives and endpoints.

In the induction phase participants who use opioids via an injection route and/or use high doses of opioids who are in withdrawal will be randomly assigned in a 2:1 ratio to extended-release buprenorphine rapid induction or SoC induction. The rapid induction arm is designed to initiate extended-release buprenorphine treatment following a single dose of transmucosal (TM) buprenorphine, while the SoC induction arm inducts the participant onto extended-release buprenorphine using a TM buprenorphine-containing product for a minimum of 7 days. All participants will receive the first injection of extended-release buprenorphine on Day 1 and the second injection on Day 8.

Participants eligible to continue treatment in the maintenance phase will be randomized at Week 6 prior to Injection 3 in a 1:1 ratio to receive maintenance doses of either 300 mg or 100 mg extended-release buprenorphine every 4 weeks for a total of up to 8 maintenance injections.

Eligibility criteria: Inclusion Criteria:

1. Has signed the informed consent form (ICF) and is able and willing to comply with the requirements and restrictions listed therein.
2. Is 18 years of age or older at the time of signing the ICF.
3. Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder (OUD).
4. Has a history of OUD as defined by documented medical history of OUD for at least 90 days immediately prior to providing informed consent.
5. Meets at least 1 of these criteria for high-risk opioid use at the Screening visit:

   1. using opioids via the injection route for an average of 5 or more days per week in the last 4 weeks.
   2. using at least 500 mg IV heroin equivalent (e.g., 1250 mg intravenous (IV) morphine) or self-reported use of any dose of highly potent synthetic opioids (fentanyl and analogues excluding transdermal patches) for an average of 5 or more days per week in the last 4 weeks by any route.
6. Is seeking medication for the treatment of OUD.
7. Is an appropriate candidate for opioid partial-agonist medications for opioid use disorder (MOUD) in the opinion of the Investigator or medically qualified sub-Investigator.
8. Agrees not to use buprenorphine-containing products other than those administered as part of study treatment for the duration of the treatment period.
9. A female participant is eligible to participate if she is not pregnant, not lactating and, if of childbearing potential, agrees not to become pregnant while on the study and to use medically acceptable means of contraception while on the study).

Exclusion Criteria:

1. Has current diagnosis, other than OUD, requiring chronic opioid treatment.
2. Has concurrent primary substance use disorder, as defined by DSM-5 criteria, other than opioid, tobacco, cannabis or alcohol use disorders.
3. Meets DSM-5 criteria for severe alcohol use disorder.
4. Has had significant traumatic injury or major surgical procedure (as defined by the Investigator) within 30 days prior to the first dose of RBP-6000 or still recovering from prior such injury or surgery.
5. Has congenital long QT syndrome, history of prolonged QT in the 3 months prior to Screening, or history of medications or other factors that are at risk for Torsades de Pointes.
6. Has abdominal area unsuitable for subcutaneous injections (e.g., nodules, scarring, lesions, excessive pigment).
7. Has history of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent.
8. Has uncontrolled intercurrent illness including, but not limited to, a medical or psychiatric illness/social situation that would limit compliance with study requirements or compromise the ability of the participant to provide written informed consent.
9. Has any other active medical condition, organ disease or concurrent medication or treatment that may either compromise participant safety or interfere with study endpoints.
10. Has total bilirubin ≥ 1.5 × upper limit of normal (ULN) (with direct bilirubin \> 1.3 mg/dL), alanine aminotransferase (ALT) ≥ 3 × ULN, aspartate aminotransferase (AST) ≥ 3 × ULN, serum creatinine \> 2 × ULN, or international normalized ratio (INR) \> 1.5 × ULN at Screening.
11. Has known allergy or hypersensitivity to buprenorphine or any component of the ATRIGEL Delivery System.
12. Is undergoing concurrent or has had prior treatment with any long-acting form of buprenorphine-containing product in the past 2 years, or if \> 2 years has a positive UDS for buprenorphine at screening; treatment with oral buprenorphine, oral naltrexone or methadone products within 14 days prior to consent; or treatment with depot naltrexone within the 3 months prior to consent.
13. Is undergoing concurrent treatment with another investigational agent or enrollment in another clinical study (except for an observational study) or treatment with another investigational agent within 30 days prior to Screening.
14. Is undergoing concurrent treatment with medications contraindicated for use with buprenorphine as per local prescribing information.
15. Has any pending legal status or pending legal action that could prohibit full participation in or compliance with study procedures.
16. Is under court order requiring treatment for OUD.
17. Is a member of site staff and/or has a financial interest in Indivior, or is an immediate family member of either the site staff and/or Indivior employee, directly involved in the study.

Primary outcomes:
measure: Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over Weeks 20 to 38
timeFrame: Weeks 20 to 38
measure: Induction Phase: Percentage of Participants Receiving Injection 2 at the Week 2 Visit
timeFrame: Week 2
Secondary outcomes:
measure: Maintenance Phase: Percentage of Days Opioids were Used over Weeks 10 to 38
timeFrame: Weeks 10 to 38
measure: Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over Weeks 10 to 38
timeFrame: Weeks 10 to 38
measure: Maintenance Phase: Percentage of Visits with Opioid Abstinence Over Weeks 10 to 38
timeFrame: Weeks 10 to 38
measure: Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over Weeks 30 to 38
timeFrame: Week 30 to 38
measure: Maintenance Phase: Percentage of Responders for Daily Opioid Use
timeFrame: Week 30 to 38
measure: Maintenance Phase: Percentage of Visits with Opioid Abstinence Overall
timeFrame: Week 2 to 38
measure: Maintenance Phase: Percentage of Days Opioids were Used Overall
timeFrame: Week 2 to 38
measure: Maintenance Phase: Percentage of Days Opioids were used via the Injection Route
timeFrame: Weeks 10 to 38
measure: Maintenance Phase: Average Number of Times Opioids were Used per Week by Visit
timeFrame: Baseline to Week 38
measure: Maintenance Phase: Change From Baseline in Number of Times Opioids were Used per Week
timeFrame: Baseline to Week 38
measure: Maintenance Phase: Percentage of Participants who were Opioid Abstinent by Visit
timeFrame: Baseline to Week 38
measure: Maintenance Phase: Average Number of Days Opioids were Used per Week by Visit
timeFrame: Baseline to Week 38
measure: Maintenance Phase: Treatment Retention
timeFrame: From randomization at Week 6 to Week 38
measure: Maintenance Phase: Percentage of Participants who Complete the Last Scheduled Injection
timeFrame: Week 34
measure: Induction Phase: Time to Treatment Discontinuation
timeFrame: Approximately 6 weeks
measure: Induction Phase: Number of Participants with Adverse Events up to Injection 2, and Between Injections 2 and 3
timeFrame: Approximately 6 weeks
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Panorama City
country: United States
facility: Asclepes Research Centers
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Bay Pines
country: United States
facility: Bay Pines VA Healthcare System
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Lakeland
country: United States
facility: Accel Research Sites- Lakeland Clinical Research Unit
state: Florida
city: Miami Lakes
country: United States
facility: Behavioral Clinical Research, Inc
state: Florida
city: North Miami
country: United States
facility: Innovative Clinical Research Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Cherry Hill
country: United States
facility: Center For Emotional Fitness
state: New Jersey
city: New York
country: United States
facility: ICAHN School of Medicine at Mount Sinai
state: New York
city: Durham
country: United States
facility: Duke Hospital
state: North Carolina
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Pahl Pharmaceutical Professionals LLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: SP Research, PLLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: Unity Clinical Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Today Clinical Research
state: Oklahoma
city: Altoona
country: United States
facility: Clinical Research Associates of Central PA
state: Pennsylvania
city: Clinton
country: United States
facility: Carolina Medical Research, LLC
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health ITOR Research Pharmacy
state: South Carolina
city: Greenville
country: United States
facility: Carolina Medical Research, LLC
state: South Carolina
city: Myrtle Beach
country: United States
facility: David Weitzman
state: South Carolina
city: DeSoto
country: United States
facility: Insite Clinical Research
state: Texas
city: Bountiful
country: United States
facility: Progressive Clinical Research
state: Utah
city: Clinton
country: United States
facility: Alpine Research Organization
state: Utah
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Indivior Inc.
name: Global Director Clinical Development
role: STUDY_DIRECTOR
References: