ALK21-003: Study of Medisorb® Naltrexone (VIVITROL®) in Alcohol-Dependent Adults

Phase 3

Completed

• Conditions: Alcoholism
• Interventions: Drug: Placebo matching Medisorb naltrexone 190 mg; Drug: Placebo matching Medisorb naltrexone 380 mg; Drug: Medisorb naltrexone 190 mg; Drug: Medisorb naltrexone 380 mg

• Registration Number: NCT01218958
• Lead Sponsor: Alkermes, Inc.

Brief Summary

This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study conducted in subjects diagnosed with alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV). Subjects were randomized (2:2:1:1) to receive intramuscular (IM) injections of Medisorb® naltrexone 190 mg, Medisorb naltrexone 380 mg, placebo for Medisorb naltrexone 190 mg, or placebo for Medisorb naltrexone 380 mg (VIVITROL®). Study drug was administered every 4 weeks for a total of 6 injections.

Detailed Description

All subjects received standardized biopsychosocial support therapy (BRENDA Approach \[Volpicelli, JR \[2001\]; Guilford Press: New York\]) at each visit.

Subjects who completed this study (ie, received 6 injections of study drug and completed all study visits) and continued to meet eligibility criteria were given the option to enroll in extension study ALK21-003EXT (NCT01218971). A second extension, Study ALK21-010 (NCT00156923), was conducted subsequent to ALK21-003EXT.

Study Timeline

• Study Start: 2002-02
• Primary Completion: 2003-09
• Study Completion: 2003-09
• Study First Submitted: 2010-10-08
• Study First Submitted QC: 2010-10-12
• Study First Posted: 2010-10-13
• Results First Submitted: 2010-11-05
• Results First Submitted QC: 2010-11-05
• Results First Posted: 2010-12-07
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-08
• Last Update Posted: 2017-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 624

Inclusion Criteria

• Diagnosis of alcohol dependence based on Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV) criteria
• Male or non-pregnant, non-lactating female
• Able to provide TimeLine Follow-Back (TLFB) alcohol consumption information for 90-day period before detoxification and/or screening
• At least 2 episodes of heavy alcohol drinking per week during the 30 days before detoxification and/or screening
• Negative urine toxicological screen for opiates on day of randomization
• Noncustodial, stable residence and phone plus 1 contact with verifiable address and phone

Primary

Exclusion Criteria

• Evidence of hepatic failure including: ascites, prolonged prothrombin time (PT) (international normalized ratio [INR] ≥1.7), bilirubin >10% above upper limit of normal (ULN) and/or esophageal variceal disease
• Active hepatitis and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) higher than 3xULN
• History of pancreatitis
• Major depression with suicidal ideation, psychosis, bipolar disorder, or psychiatric disorders that would compromise subject's ability to complete the study
• Current dependence (within past year) per DSM-IV criteria to benzodiazepines, opioids or cocaine
• Use of benzodiazepines and/or Ambien® (zolpidem tartrate) within 7 days prior to first dose of study medication
• Greater than 7 days inpatient treatment for substance use disorders within 30 days of randomization
• Use of any opioids and/or methadone within 14 days of screening, or likely requiring opioid therapy during study period
• Use of oral naltrexone or disulfiram within 14 days of screening
• Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or polylactide-co-glycolide (PLG)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo for Medisorb naltrexone 190 mg	Placebo matching Medisorb naltrexone 190 mg	-
Placebo for Medisorb naltrexone 380 mg	Placebo matching Medisorb naltrexone 380 mg	-
Medisorb naltrexone 190 mg	Medisorb naltrexone 190 mg	-
Medisorb naltrexone 380 mg	Medisorb naltrexone 380 mg	-

Primary Outcome Measures

Name	Time	Method
Percentage of Heavy Drinking Days Over the Treatment Period	Baseline through Week 24 (168 days)	Drinking rates were assessed from participants' self-reports using the validated Timeline Follow-Back (TLFB) method. Using a TLFB calendar, participants reported the number of days they had consumed alcohol along with the amount they consumed on each day. A heavy drinking day was defined as ≥5 drinks/day for men and ≥4 drinks/day for women.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Reporting at Least 1 Treatment-emergent Adverse Event (TEAE)	24 weeks (Baseline to Week 24)	A TEAE is any adverse event, whether or not considered drug-related, that develops or worsens in severity after study drug administration begins (ie, from the first administration through the end of the follow-up period).