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

Study Overview
=================
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.

Official Title
-----------------
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Medisorb® Naltrexone in Alcohol-Dependent Adults

Conditions
-----------------
Alcoholism

Intervention / Treatment
-----------------
* Drug: Medisorb naltrexone 190 mg
* Drug: Medisorb naltrexone 380 mg
* Drug: Placebo matching Medisorb naltrexone 190 mg
* Drug: Placebo matching Medisorb naltrexone 380 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Primary 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medisorb naltrexone 190 mg<br> | Drug: Medisorb naltrexone 190 mg<br>* Intramuscular (IM) injection once every 4 weeks for a total of 6 administrations.<br>* Other names: naltrexone for extended-release injectable suspension;|
| Experimental: Medisorb naltrexone 380 mg<br> | Drug: Medisorb naltrexone 380 mg<br>* IM injection once every 4 weeks for a total of 6 administrations.<br>* Other names: naltrexone for extended-release injectable suspension;|
| Placebo Comparator: Placebo for Medisorb naltrexone 190 mg<br> | Drug: Placebo matching Medisorb naltrexone 190 mg<br>* IM injection once every 4 weeks for a total of 6 administrations.<br>|
| Placebo Comparator: Placebo for Medisorb naltrexone 380 mg<br> | Drug: Placebo matching Medisorb naltrexone 380 mg<br>* IM injection once every 4 weeks for a total of 6 administrations.<br>* Other names: Placebo matching VIVITROL 380 mg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Heavy Drinking Days Over the Treatment Period | 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. | Baseline through Week 24 (168 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting at Least 1 Treatment-emergent Adverse Event (TEAE) | 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). | 24 weeks (Baseline to Week 24) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcoholism