Evaluating Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, and tolerability of oral naltrexone used in conjunction with buprenorphine in adults with Opioid Use Disorder transitioning from buprenorphine maintenance prior to the first dose of VIVITROL.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety, Tolerability, and Efficacy of Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Naltrexone
* Drug: Placebo
* Drug: Buprenorphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent Willing and able to provide government-issued identification Has a Body Mass Index (BMI) of 18.0-40.0 kg/m^2 Has a history of opioid use disorder diagnosis for at least 6 months Has a history of prescribed buprenorphine (or buprenorphine/naloxone) maintenance for the prior 3 or more consecutive months and is currently buprenorphine-maintained Must be voluntarily seeking treatment for opioid use disorder and be motivated to receive antagonist therapy Willing to abide by the contraception requirements for the duration of the study Additional criteria may apply Exclusion Criteria: Is pregnant, planning to become pregnant or breastfeeding during the study Has a positive urine drug screen for opiates or oxycodone at screening Has used methadone within 30 days prior to study Day -5 Has used naltrexone (oral or VIVITROL) within the 90 days prior to Day -5 Has a history of seizures or has received anticonvulsant therapy within the past 5 years for treatment of seizures (use of anticonvulsant during the past detoxification is not exclusionary) Has a condition, disease state, or previous medical history that would preclude safe participation in the study or affect the ability to adhere to the protocol visit schedule, requirements, or assessments Has a current diagnosis of schizoaffective disorder, bipolar disorder, or untreated and unstable major depressive disorder Is currently physiologically dependent on any psychoactive substance (except opioids, caffeine, or nicotine) requiring medical intervention for detoxification Has a history of hypersensitivity or adverse reaction to buprenorphine, naltrexone, VIVITROL, or naloxone Additional criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 |
| --- | --- |
| Active Comparator: PBO NTX + BUP<br>Placebo naltrexone + buprenorphine | Drug: Placebo<br>* daily dosing<br>Drug: Buprenorphine<br>* daily dosing<br>|
| Experimental: NTX + BUP<br>Naltrexone + buprenorphine | Drug: Naltrexone<br>* daily dosing<br>Drug: Buprenorphine<br>* daily dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8 | Demonstrated by mild opioid withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] </=12 or Subjective Opiate Withdrawal Scale [SOWS] </=10) following VIVITROL administration. The COWS is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal). The SOWS is a 16-item self-report questionnaire designed to measure the severity of opioid withdrawal symptoms. The subject rates the intensity of symptoms using a 5-point scale. The range of SOWS scores is 1-10 (mild); 11-20 (moderate); and 21-30 (severe). | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection | The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal). | 1 week | 
| Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal | COWS score </=12; The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal). | Days 9-11 | 
| Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7) | The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal). | Up to 7 days | 
| Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | The Clinical Opiate Withdrawal Scale (COWS) is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal). The daily AUC COWS score is derived based on the actual time (unit in minutes) COWS administered on each day by using the linear trapezoidal rule, and then divided by the COWS administration duration (last COWS administration time minus first COWS administration time) for that day. The normalized AUC COWS score is the summation of daily AUC COWS score during the relevant period divided by the number of days with daily AUC COWS score. | The COWS was administered 4-6 times per day during the Treatment Period | 
| Mean Score for Desire for Opioids Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period | The Desire for Opioids VAS uses a 100-mm, horizontal linear scale, with 0 anchored on the left representing no desire for opioids and 100 anchored on the right representing strongest imaginable desire for opioids. | Up to 11 days | 
| Incidence of Adverse Events (AEs) | Number and percentage of subjects who experienced AEs. | Up to 42 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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naltrexone, VIVITROL, buprenorphine, opioid, addiction