ALK21-013: Efficacy and Safety of Medisorb® Naltrexone (VIVITROL®) in Adults With Opioid Dependence

Study Overview
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Brief Summary
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This is a Phase 3 multi-center trial designed to evaluate the clinical efficacy and safety of VIVITROL® (Medisorb® naltrexone 380 mg) versus placebo when administered to adults upon discharge from inpatient treatment for opioid dependence. The study was conducted in 2 parts, Part A and Part B. The clinical portion of both parts has completed. Results for Part B are not yet available.

Detailed Description
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Part A was a double-blind, randomized, placebo-controlled assessment of the efficacy and safety of 24 weeks of monthly treatment with VIVITROL compared to placebo in opioid-dependent adults. Subjects who completed Part A could choose to continue to Part B, which was an open-label extension to assess longer-term safety, durability of effect, health economics, and quality of life (QOL) in the continuing study population for up to 1 year. At the conclusion of both parts, each completing subject will have received a total of up to 19 injections of study drug over approximately 1.5 years. Dosing was performed by the principal investigator or designated study staff member. All subjects received standardized, manual-based psychosocial support at each scheduled visit. Opioid use was tracked through urine drug testing and subjects' self reports. Other evaluations for efficacy and safety, health economics, and quality of life were routinely conducted throughout the study.

Official Title
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Efficacy and Safety of VIVITROL® (Naltrexone for Extended-release Injectable Suspension) in Adults With Opioid Dependence

Conditions
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Opiate Dependence

Intervention / Treatment
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* Drug: VIVITROL® 380 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Primary Inclusion Criteria: Written, informed consent 18 years of age or older Current diagnosis of opioid dependence, based on Diagnostic and Statistical Manual of Mental Health Disorders, 4th Ed. (DSM-IV-TR) criteria Voluntarily seeking treatment for opioid dependence Completing or recently completed up to 30 days of inpatient treatment for opioid detoxification, and off all opioids (including buprenorphine and methadone) for at least 7 days Noncustodial, stable residence and phone, plus 1 contact with verifiable address and phone Significant other (eg, spouse, relative) willing to supervise compliance with the study visit schedule and procedures Agree to use contraception for study duration if of childbearing potential Primary Exclusion Criteria: Pregnancy or lactation Clinically significant medical condition or observed abnormalities (eg: physical exam, electrocardiogram (ECG), lab and/or urinalysis findings) Positive naloxone challenge test at randomization (Day 0) Evidence of hepatic failure including: ascites, bilirubin >10% above upper limit of normal (ULN) and/or esophageal variceal disease Past or present history of an acquired immunodeficiency syndrome (AIDS)-indicator disease in HIV-infected subjects Active hepatitis and/or aspartate aminotransferase (AST), alanine aminotransferase(ALT) >3xULN Current major depression with suicidal ideation, psychosis, bipolar disorder, or any psychiatric disorder that would compromise ability to complete the study Recent history (within 6 months prior to screening) of suicidal ideation or attempt Dependence within prior year based on DSM-IV-TR, to any drugs other than prescription opioids or heroin, caffeine, marijuana, or nicotine Active alcohol dependence within prior 6 months Current alcohol use disorder that would, in the Investigator's opinion, preclude successful completion of the study Positive urine drug test for cocaine, benzodiazepines, or amphetamines at screening Use of oral naltrexone for 7 consecutive days within 60 days prior to screening Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or polylactide-co-glycolide (PLG)

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIVITROL® 380 mg<br> | Drug: VIVITROL® 380 mg<br>* Administered via intramuscular (IM) injection once every 4 weeks for 24 weeks during Part A, followed by once every 4 weeks for 52 weeks in Part B.<br>* Other names: Medisorb® naltrexone;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered via IM injection once every 4 weeks for 24 weeks during Part A, followed by VIVITROL® 380 mg via IM injection once every 4 weeks for 52 weeks in Part B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A) | Included are data from the last 20 weeks of the 24-week double-blind treatment period (Part A). Response profiles for each Arm are based on subjects' individual rates of weekly opioid-free data, including negative urine test results, attendance at study visits, and self-reports of opioid use/non-use. | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days to Discontinuation During Part A | Defined as the duration of study participation and calculated as the number of days from Dose 1 to the day of study discontinuation. | 168 days (24 weeks) | 
| Craving Score: Change From Baseline | Measured using subjects' response on a validated Visual Analog Scale at prespecified weekly visits throughout Part A, with comparison of baseline to end of Part A. The scale ranged from 0 (No craving) to 100 (highest possible craving). | Baseline to 6 months (24 weeks) | 
| Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A) | Assessment of relapse to physiologic opioid dependence was based on individual subjects' results on the naloxone challenge test. A positive naloxone challenge test result was considered as a relapse to physiologic opioid dependence. | 24 Weeks | 
| Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24 | Opioid use was measured using subjects' entries on a validated Timeline FollowBack (TLFB) calendar in which they recorded their use/non-use of opioids each day. | 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Addiction, Opiate dependence, Inpatient detoxification, opioid dependence, heroin dependence