Clinical trial NCT01218958: ALK21-003: Study of Medisorb® Naltrexone (VIVITROL®) in Alcohol-Dependent Adults
Official title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Medisorb® Naltrexone in Alcohol-Dependent Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alcoholism
Keywords: Alcoholism
Lead sponsor: Alkermes, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-13
Enrollment: 624
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Percentage of Heavy Drinking Days Over the Treatment Period
timeFrame: Baseline through Week 24 (168 days)
Secondary outcomes:
measure: Number of Participants Reporting at Least 1 Treatment-emergent Adverse Event (TEAE)
timeFrame: 24 weeks (Baseline to Week 24)
Other outcomes:
Locations:
Study officials:
affiliation: Alkermes, Inc.
name: Bernard Silverman, MD
role: STUDY_DIRECTOR
References:
citation: Garbutt JC, Kranzler HR, O'Malley SS, Gastfriend DR, Pettinati HM, Silverman BL, Loewy JW, Ehrich EW; Vivitrex Study Group. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005 Apr 6;293(13):1617-25. doi: 10.1001/jama.293.13.1617.
citation: O'Malley SS, Garbutt JC, Gastfriend DR, Dong Q, Kranzler HR. Efficacy of extended-release naltrexone in alcohol-dependent patients who are abstinent before treatment. J Clin Psychopharmacol. 2007 Oct;27(5):507-12. doi: 10.1097/jcp.0b013e31814ce50d.
citation: Gastfriend DR, Garbutt JC, Pettinati HM, Forman RF. Reduction in heavy drinking as a treatment outcome in alcohol dependence. J Subst Abuse Treat. 2007 Jul;33(1):71-80. doi: 10.1016/j.jsat.2006.09.008. Epub 2007 Feb 22.
citation: Lucey MR, Silverman BL, Illeperuma A, O'Brien CP. Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics. Alcohol Clin Exp Res. 2008 Mar;32(3):498-504. doi: 10.1111/j.1530-0277.2007.00593.x. Epub 2008 Jan 30.
citation: Ciraulo DA, Dong Q, Silverman BL, Gastfriend DR, Pettinati HM. Early treatment response in alcohol dependence with extended-release naltrexone. J Clin Psychiatry. 2008 Feb;69(2):190-5. doi: 10.4088/jcp.v69n0204.
citation: Pettinati HM, Gastfriend DR, Dong Q, Kranzler HR, O'Malley SS. Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients. Alcohol Clin Exp Res. 2009 Feb;33(2):350-6. doi: 10.1111/j.1530-0277.2008.00843.x. Epub 2008 Nov 25.
citation: Lapham S, Forman R, Alexander M, Illeperuma A, Bohn MJ. The effects of extended-release naltrexone on holiday drinking in alcohol-dependent patients. J Subst Abuse Treat. 2009 Jan;36(1):1-6. doi: 10.1016/j.jsat.2008.07.001. Epub 2008 Sep 4.
citation: Cisler RA, Silverman BL, Gromov I, Gastfriend DR. Impact of treatment with intramuscular, injectable, extended-release naltrexone on counseling and support group participation in patients with alcohol dependence. J Addict Med. 2010 Sep;4(3):181-5. doi: 10.1097/ADM.0b013e3181c82207.
citation: Pettinati HM, Silverman BL, Battisti JJ, Forman R, Schweizer E, Gastfriend DR. Efficacy of extended-release naltrexone in patients with relatively higher severity of alcohol dependence. Alcohol Clin Exp Res. 2011 Oct;35(10):1804-11. doi: 10.1111/j.1530-0277.2011.01524.x. Epub 2011 May 16.