Buprenorphine Extended-Release Subcutaneous Injection (RBP-6000) in High-risk Users

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Moderate to Severe Opioid-use Disorder

Intervention / Treatment
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* Drug: Transmucosal Buprenorphine
* Drug: Extended-release Buprenorphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed the informed consent form (ICF) and is able and willing to comply with the requirements and restrictions listed therein. Is 18 years of age or older at the time of signing the ICF. Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder (OUD). Has a history of OUD as defined by documented medical history of OUD for at least 90 days immediately prior to providing informed consent. Meets at least 1 of these criteria for high-risk opioid use at the Screening visit: using opioids via the injection route for an average of 5 or more days per week in the last 4 weeks. 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. Is seeking medication for the treatment of OUD. 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. Agrees not to use buprenorphine-containing products other than those administered as part of study treatment for the duration of the treatment period. 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: Has current diagnosis, other than OUD, requiring chronic opioid treatment. Has concurrent primary substance use disorder, as defined by DSM-5 criteria, other than opioid, tobacco, cannabis or alcohol use disorders. Meets DSM-5 criteria for severe alcohol use disorder. 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. 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. Has abdominal area unsuitable for subcutaneous injections (e.g., nodules, scarring, lesions, excessive pigment). 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. 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. Has any other active medical condition, organ disease or concurrent medication or treatment that may either compromise participant safety or interfere with study endpoints. 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. Has known allergy or hypersensitivity to buprenorphine or any component of the ATRIGEL Delivery System. 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. 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. Is undergoing concurrent treatment with medications contraindicated for use with buprenorphine as per local prescribing information. Has any pending legal status or pending legal action that could prohibit full participation in or compliance with study procedures. Is under court order requiring treatment for OUD. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction Phase: Rapid Induction<br>Participants will receive 4 mg transmucosal buprenorphine on Day 1. Participants meeting eligibility requirements will then receive 300 mg extended-release buprenorphine by subcutaneous injection at least 1 hour later and a second dose on Day 8. | Drug: Transmucosal Buprenorphine<br>* Transmucosal (TM) buprenorphine as selected by the Investigator per local prescribing guidelines, administered either under the tongue (sublingual) or between the gum and cheek (buccal)<br>Drug: Extended-release Buprenorphine<br>* Administered by subcutaneous injection<br>* Other names: SUBLOCADE;|
| Experimental: Induction Phase: Standard of Care Induction<br>Participants will receive transmucosal buprenorphine for a minimum of 7 days per applicable product labelling information. Participants meeting eligibility requirements will receive 300 mg extended-release buprenorphine by subcutaneous injection on Day 1 and a second dose on Day 8. | Drug: Transmucosal Buprenorphine<br>* Transmucosal (TM) buprenorphine as selected by the Investigator per local prescribing guidelines, administered either under the tongue (sublingual) or between the gum and cheek (buccal)<br>Drug: Extended-release Buprenorphine<br>* Administered by subcutaneous injection<br>* Other names: SUBLOCADE;|
| Experimental: Maintenance Phase: Extended-release Buprenorphine 100 mg<br>Participants eligible to continue treatment will be randomized at Week 6 to receive maintenance doses of 100 mg extended-release buprenorphine by subcutaneous injection every 4 weeks for a total of up to 8 maintenance injections (Weeks 6 to 34). | Drug: Extended-release Buprenorphine<br>* Administered by subcutaneous injection<br>* Other names: SUBLOCADE;|
| Experimental: Maintenance Phase: Extended-release Buprenorphine 300 mg<br>Participants eligible to continue treatment will be randomized at Week 6 to receive maintenance doses of 300 mg extended-release buprenorphine by subcutaneous injection every 4 weeks for a total of up to 8 maintenance injections (Weeks 6 to 34). | Drug: Extended-release Buprenorphine<br>* Administered by subcutaneous injection<br>* Other names: SUBLOCADE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction Phase: Percentage of Participants Receiving Injection 2 at the Week 2 Visit |  | Week 2 | 
| Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over Weeks 10 to 38 | A responder for weekly opioid use is defined as a participant whose percentage of visits with opioid abstinence is greater than or equal to 80% over Weeks 10 to 38 inclusive. Opioid abstinence is defined as a negative urine drug screen (UDS) result and negative responses to the TimeLine Follow Back (TLFB) interview for opioid use. The TLFB asks participants to retrospectively estimate their daily drug use for each of the past 7 days prior to the visit. Opioid use will be assessed at 15 visits between Weeks 10 and 38. | Weeks 10 to 38 | 
| Maintenance Phase: Percentage of Days Opioids were Used over Weeks 10 to 38 | Participants' percentage of days opioids were used out of days assessed over Weeks 10 to 38 (inclusive), based on the TLFB for the prior week at a total of 15 visits. | Weeks 10 to 38 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction Phase: Time to Treatment Discontinuation | Time to treatment discontinuation is defined as the number of days from the first dose of TM buprenorphine until the last scheduled visit observed during the open-label treatment period. | Approximately 7 weeks | 
| Induction Phase: Number of Participants with Adverse Events up to Injection 2, and Between Injections 2 and 3 |  | Approximately 7 weeks | 
| Maintenance Phase: Percentage of Visits with Opioid Abstinence Over Weeks 10 to 38 | Opioid abstinence is defined as negative urine drug screen results and negative responses to the TLFB interview for opioids, assessed at 15 visits between Weeks 10 and 38. The TLFB asks participants to retrospectively estimate their daily drug use for each of the past 7 days prior to the visit. | Weeks 10 to 38 | 
| Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over Weeks 20 to 38 and Weeks 30 to 38 | A responder for weekly opioid use is defined as a participant whose percentage of visits with opioid abstinence is greater than or equal to 80% for the last 5 visits (Weeks 30 to 38) or over the last 10 visits (Weeks 20 to 38). Opioid abstinence is defined as a negative UDS result and negative responses to the TLFB interview for opioid use. The TLFB asks participants to retrospectively estimate their daily drug use for each of the past 7 days prior to the visit. | Week 30 to 38 and Week 20 to 38 | 
| Maintenance Phase: Percentage of Responders for Daily Opioid Use | A responder for daily opioid use is defined as a participant with 20% or less days of opioid use, based on the TLFBs collected at the last 5 observed visits post randomization. The TLFB asks participants to retrospectively estimate their daily drug use for each of the past 7 days prior to the visit. | Week 30 to 38 | 
| Maintenance Phase: Percentage of Visits with Opioid Abstinence Overall | Opioid abstinence is defined as negative urine drug screen results and negative responses to the TLFB interview for opioids at all assessments between Weeks 2 and 38. The TLFB asks participants to retrospectively estimate their daily drug use for each of the past 7 days prior to the visit. | Week 2 to 38 | 
| Maintenance Phase: Percentage of Days Opioids were Used Overall | For each participant, the percentage of days opioids were used out of days assessed over Weeks 2 to 38 (inclusive), based on the TLFB for the prior week of each visit. | Week 2 to 38 | 
| Maintenance Phase: Percentage of Days Opioids were used via the Injection Route | For participants who use opioids via the injection route for an average of 5 or more days per week in the last 4 weeks prior to Screening, the percentage of days opioids were used via the injection route out of days assessed based on the TLFB interview for the prior week of each visit. | Weeks 10 to 38 | 
| Maintenance Phase: Average Number of Times Opioids were Used per Week by Visit | The average number of times opioids were used per week for a given visit based on the TLFB for the prior week collected at that visit. | Baseline to Week 38 | 
| Maintenance Phase: Change From Baseline in Number of Times Opioids were Used per Week | The change in participants' number of times opioids were used per week from randomization baseline to each visit based on the 7 daily TLFB for the prior week collected at that visit. | Baseline to Week 38 | 
| Maintenance Phase: Percentage of Participants who were Opioid Abstinent by Visit | Opioid abstinence is defined as negative urine drug screen results and negative responses to the TLFB interview for opioids. | Baseline to Week 38 | 
| Maintenance Phase: Average Dumber of Days Opioids were Used per Week by Visit | The average number of days opioids were used per week out of days assessed, based on the TLFB for the prior week of each visit. | Baseline to Week 38 | 
| Maintenance Phase: Treatment Retention | Treatment retention is defined as the number of days from randomization in the maintenance phase until the date of discontinuation. | From randomization at Week 6 to Week 38 | 
| Maintenance Phase: Percentage of Participants who Complete the Last Scheduled Injection |  | Week 34 |