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

Indivior Inc.785 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

785

Conditions

Moderate to Severe Opioid-use Disorder

Interventions

Transmucosal BuprenorphineDRUG

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)

Extended-release BuprenorphineDRUG

Administered by subcutaneous injection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (29)

Outcomes

Primary Outcomes

Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over Weeks 20 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 20 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.

Time frame: Weeks 20 to 38

Induction Phase: Percentage of Participants Receiving Injection 2 at the Week 2 Visit

Treatment retention at Injection 2 was defined as the proportion of participants receiving Injection 2 at the Week 2 Visit among those in the Evaluable Population for Treatment Retention/Discontinuation. Participants who received Injection 2 at Week 2 (nominal) Visit and those who missed Injection 2 at Week 2 (nominal) Visit but received Injection 3 at the Week 6 Day 36 Visit were counted as "Yes" for treatment retention at Injection 2; otherwise, participants were counted as "No".

Time frame: Week 2

Secondary Outcomes

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.

Time frame: Weeks 10 to 38

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.

Data from ClinicalTrials.gov

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Time frame: Weeks 10 to 38

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 TimeLine Follow Back (TLFB) interview for opioids. The TLFB asks participants to retrospectively estimate their daily drug use for each of the past 7 days prior to the visit.

Time frame: Weeks 10 to 38

Maintenance Phase: Percentage of Responders for Weekly Opioid Use Over 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 planned for urine drug screen (UDS) and TimeLine Follow Back (TLFB) over Weeks 30 to 38 (inclusive). 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.

Time frame: Week 30 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 TimeLine Follow Backs (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.

Time frame: 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 TimeLine Follow Back (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.

Time frame: 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 TimeLine Follow Back (TLFB) for the prior week of each visit.

Time frame: 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 Timeline Follow Back (TLFB) interview for the prior week of each visit.

Time frame: 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 TimeLine Follow Back (TLFB) for the prior week collected at that visit.

Time frame: 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 TimeLine Follow Back (TLFB) for the prior week collected at that visit.

Time frame: 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 TimeLine Follow Back (TLFB) interview for opioids.

Time frame: Baseline to Week 38

Maintenance Phase: Average Number 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 TimeLine Follow Back (TLFB) for the prior week of each visit.

Time frame: Baseline to Week 38

Maintenance Phase: Time From DB Randomization to Last Observed Study Visit (Treatment Retention)

Treatment retention is defined as the number of days that participants remained in the treatment from randomization in the Maintenance Phase of the study until the date of the last observed study visit. The treatment retention since DB randomization is estimated using Kaplan-Meier method. The event is prematurely discontinuing the study prior to Week 38/EOT Visit.

Time frame: Up to 288 days after randomization (accounting for out-of-window visits)

Maintenance Phase: Percentage of Participants Who Complete the Last Scheduled Injection

The proportion of randomized participants who completed the last scheduled injection of RBP-6000 at Week 34 were summarized using observed data. Missing data were not applicable for this endpoint.

Time frame: Week 34

Induction Phase: Percentage of Participants Retained at 5 Weeks

Percentage of participants retained at 5 weeks after the first dose of TM buprenorphine was estimated using the Kaplan-Meier product limit method.

Time frame: 35 days

Induction Phase: Number of Participants With Adverse Events up to Injection 2

These endpoints encompassed all induction attempts and therefore utilized the first dose of transmucosal buprenorphine (TM BUP) for derivations. A treatment-emergent adverse event (TEAE) was defined as an AE having an onset date/time after administration of the first TM BUP dose and before the date/time of Injection 3. TEAEs up to RBP-6000 Injection 2 were TEAEs with a start date/time on or after the first dose of TM BUP and before the date/time of Injection 2.

Time frame: Up to approximately 2 weeks

Induction Phase: Number of Participants With Adverse Events Between Injections 2 and 3

These endpoints encompassed all induction attempts and therefore utilized the first dose of transmucosal buprenorphine (TM BUP) for derivations. A treatment-emergent adverse event (TEAE) was defined as an AE having an onset date/time after administration of the first TM BUP dose and before the date/time of Injection 3. TEAEs between RBP-6000 Injections 2 and 3 were TEAEs with a start date/time on or after Injection 2 and before the date/time of Injection 3.

Time frame: Approximately 4 weeks