ALK21-003: Study of Medisorb® Naltrexone (VIVITROL®) in Alcohol-Dependent Adults
Primary Purpose
Alcoholism
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Medisorb naltrexone 190 mg
Medisorb naltrexone 380 mg
Placebo matching Medisorb naltrexone 190 mg
Placebo matching Medisorb naltrexone 380 mg
Sponsored by
About this trial
This is an interventional treatment trial for Alcoholism focused on measuring Alcoholism
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
Medisorb naltrexone 190 mg
Medisorb naltrexone 380 mg
Placebo for Medisorb naltrexone 190 mg
Placebo for Medisorb naltrexone 380 mg
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01218958
Brief Title
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
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
February 2002 (undefined)
Primary Completion Date
September 2003 (Actual)
Study Completion Date
September 2003 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Alkermes, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholism
Keywords
Alcoholism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
624 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Medisorb naltrexone 190 mg
Arm Type
Experimental
Arm Title
Medisorb naltrexone 380 mg
Arm Type
Experimental
Arm Title
Placebo for Medisorb naltrexone 190 mg
Arm Type
Placebo Comparator
Arm Title
Placebo for Medisorb naltrexone 380 mg
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Medisorb naltrexone 190 mg
Other Intervention Name(s)
naltrexone for extended-release injectable suspension
Intervention Description
Intramuscular (IM) injection once every 4 weeks for a total of 6 administrations.
Intervention Type
Drug
Intervention Name(s)
Medisorb naltrexone 380 mg
Other Intervention Name(s)
VIVITROL 380 mg, naltrexone for extended-release injectable suspension
Intervention Description
IM injection once every 4 weeks for a total of 6 administrations.
Intervention Type
Drug
Intervention Name(s)
Placebo matching Medisorb naltrexone 190 mg
Intervention Description
IM injection once every 4 weeks for a total of 6 administrations.
Intervention Type
Drug
Intervention Name(s)
Placebo matching Medisorb naltrexone 380 mg
Other Intervention Name(s)
Placebo matching VIVITROL 380 mg
Intervention Description
IM injection once every 4 weeks for a total of 6 administrations.
Primary Outcome Measure Information:
Title
Percentage of Heavy Drinking Days Over the Treatment Period
Description
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.
Time Frame
Baseline through Week 24 (168 days)
Secondary Outcome Measure Information:
Title
Number of Participants Reporting at Least 1 Treatment-emergent Adverse Event (TEAE)
Description
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).
Time Frame
24 weeks (Baseline to Week 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernard Silverman, MD
Organizational Affiliation
Alkermes, Inc.
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
15811981
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. Erratum In: JAMA. 2005 Apr 27;293(16):1978. JAMA. 2005 Jun 15:293(23):2864.
Results Reference
result
PubMed Identifier
17873686
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.
Results Reference
result
PubMed Identifier
17588491
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.
Results Reference
result
PubMed Identifier
18241321
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.
Results Reference
result
PubMed Identifier
18348601
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.
Results Reference
result
PubMed Identifier
19053979
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.
Results Reference
result
PubMed Identifier
18775624
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.
Results Reference
result
PubMed Identifier
21769033
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.
Results Reference
result
PubMed Identifier
21575016
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.
Results Reference
result
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ALK21-003: Study of Medisorb® Naltrexone (VIVITROL®) in Alcohol-Dependent Adults
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