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

Phase 3

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
VIVITROL® 380 mg	VIVITROL® 380 mg	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A)	20 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24	24 Weeks	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.
Craving Score: Change From Baseline	Baseline to 6 months (24 weeks)	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").
Days to Discontinuation During Part A	168 days (24 weeks)	Defined as the duration of study participation and calculated as the number of days from Dose 1 to the day of study discontinuation.
Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A)	24 Weeks	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.