Multiple Dose Study of Blockade of Opioid Effects by Injections of Buprenorphine in Participants With Opioid Disorder

Indivior

Status and phase: Completed; Phase 2

Conditions: Opioid Use Disorder

Treatments: Drug: buprenorphine and naloxone; Drug: hydromorphone; Drug: placebo; Drug: Buprenorphine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02044094

RB-US-13-0002

Details and patient eligibility

About

This is a multiple-dose study in non-treatment seeking male and female subjects with moderate to severe opioid use disorder who meet criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) to evaluate the effectiveness of RBP-6000 to block the effects of exogenous opioids.

The primary objective of this study was to demonstrate that the "Drug Liking" visual analog scale (VAS) measured after challenge with 6 mg (Dose 1) and 18 mg (Dose 2) hydromorphone was noninferior to the "Drug Liking" visual analog scale (VAS) measured after challenge with placebo at Weeks 1-4 post first injection of subcutaneous buprenorphine 300 mg (RBP-6000).

Full description

For the hydromorphone challenge testing, subjects were randomized and assigned to 1 of 6 sequences during each week of hydromorphone challenge sessions.

On Day -18, subjects who met initial eligibility criteria were admitted to the clinical facility for the baseline hydromorphone challenge. If the subject had acceptable hydromorphone responses to the hydromorphone challenge, they remained confined to the clinical facility for induction on SUBOXONE sublingual film. Once it was confirmed that a subject was experiencing opioid withdrawal, as evidenced by a Clinical Opiate Withdrawal Scale (COWS) score greater than 12, the subject was inducted on SUBOXONE sublingual film. Multiple doses were allowed while subjects were reaching a stable dose until Day -9 when subjects were stabilized on a dose of SUBOXONE 8 mg - 24 mg. SUBOXONE sublingual film was administered daily at approximately the same time of day (± 1 hour) once the dose was stabilised. There was a hydromorphone challenge conducted on days -3 to -1. The last day of SUBOXONE dosing was day -1.

On Day 1, participants who met all inclusion/exclusion criteria and dosing criteria stopped receiving SUBOXONE sublingual film and received Injection 1 of RBP-6000 containing 300 mg buprenorphine. Participants returned in the evening of Days 4, 11, 18, and 25 to begin inpatient stays of 3 consecutive days (starting with Days 4-7 [and equivalent for subsequent weeks]). During these inpatient visits, subjects underwent randomised hydromorphone challenges, PK sample collection, Reinforcing Effects Tasks, and safety assessments.

On Day 29, participants received the second injection of RBP-6000 containing 300 mg buprenorphine (Injection 2). Participants returned in the evening on Days 32, 39, 46, 53, 60, 67, 74, and 81 to begin inpatient states of 3 consecutive days (starting with days 32-35 [and equivalent for subsequent weeks]). During these inpatient visits, subjects underwent randomised hydromorphone challenges, pharmacokinetic (PK) samples collection, Reinforcing Effects Tasks, and safety assessments. A window of ± 1 day was allowed for all visits, except the Day 53-56 visit, which was required by the protocol to be completed on those days.

Enrollment: 39 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for moderate or severe opioid use disorder at screening and are not seeking opioid use disorder treatment
• Body mass index of >= 18.0 to <= 33.0 kg/m^2
• Females - women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have negative pregnancy test prior to enrollment and must agree to use a medically acceptable means of contraception from screening through at least 3 months after the last dose of study drug
• Male subjects with female partners of child-bearing potential must agree to use medically acceptable contraception from screening through at least 3 months after the last dose of study drug

Exclusion criteria

• Subjects with any current diagnosis requiring chronic opioid treatment
• Subjects who currently meet the criteria for diagnosis of moderate or severe substance use disorder by DSM-5 criteria for any substances other than opioids, caffeine, or nicotine.
• Subjects who have abused or used buprenorphine within 14 days prior to informed consent.

Other protocol-defined criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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39 participants in 1 patient group

depot buprenorphine

Experimental group

Description:

Participants were treated with RBP-6000 300-mg in a single subcutaneous injection on Days 1 and 29 following a prior 14 day stabilization period (day -14 to day -1) of buprenorphine and naloxone (SUBOXONE) . Challenges consist of participants receiving on three consecutive days intramuscular (IM) injections of hydromorphone 0 mg (placebo), 6 mg and 18 mg doses during weeks 1-12 in randomized sequential order.

Treatment:

Drug: Buprenorphine

Drug: placebo

Drug: hydromorphone

Drug: buprenorphine and naloxone