Safety and Efficacy of Nalmefene in Patients With Alcohol Dependence

Study Overview
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Brief Summary
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The purpose of the study is long-term safety, tolerability and efficacy of nalmefene in patients with alcohol dependence.

Detailed Description
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Alcohol dependence is a maladaptive pattern of alcohol use, leading to clinically significant impairment or distress, as manifested by at least three of a number of criteria such as tolerance, withdrawal symptoms, frequent use of alcohol in larger amounts or over longer periods than was intended, and others. Excessive intake of alcohol reduces the life span by a decade, and alcohol drinking is strongly related to mortality from liver cirrhosis, chronic pancreatitis, certain cancers, hypertension, accidents and violence. This study is planned to evaluate the long-term safety and tolerability as well as to evaluate the efficacy of as needed use of 18.06 mg nalmefene in patients with alcohol dependence.

Official Title
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A 52-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Safety, Tolerability and Efficacy Study of Nalmefene, as Needed Use, in Patients With Alcohol Dependence

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: Placebo
* Drug: Nalmefene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In- and outpatients who: had a primary diagnosis of alcohol dependence according to Diagnostic and Statistical Manual of Mental Disorders - text revision (DSM-IV-TR) criteria had had ≥6 Heavy Drinking Days (HDDs) in the 4 weeks preceding the Screening Visit Exclusion Criteria: The patient: had a severe psychiatric disorder or an antisocial personality disorder had risk of suicide evaluated by the suicidality module of the Mini-International Neuropsychiatric Interview (MINI) had a history of delirium tremens or alcohol withdrawal seizures reported current or recent (within 3 months preceding screening) treatment with disulfiram, acamprosate, topiramate, naltrexone or carbimide, or with any opioid antagonists was pregnant or breast-feeding Other protocol-defined inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* as-needed use, tablets, orally, 52 weeks<br>|
| Experimental: Nalmefene<br> | Drug: Nalmefene<br>* 18.06 mg as-needed use, tablets, orally, 52 weeks. 18.06 mg nalmefene equals 20 mg nalmefene hydrochloride.<br>* Other names: Selincro™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events (AEs) | Overview of AEs | Serious Adverse Events: 52 weeks and a safety follow-up (visit/telephone call) scheduled for 4 weeks after completion of the study or after withdrawal from the study. Other Adverse Events: 52 weeks. | 
| Percentage of Patients Who Withdrew Due to Intolerance to Treatment |  | Baseline to Week 52 | 
| Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs) | Number of HDDs over a month (28 days), where one HDD was defined as a day with alcohol consumption ≥60 grams (g) for men and ≥40 g for women. | Baseline and Month 6 | 
| Change From Baseline in the Monthly Total Alcohol Consumption (TAC) | TAC was defined as mean daily alcohol consumption in g/day over a month (28 days). | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drinking Risk Level (RSDRL) Response | RSDRL response was defined as a downward shift from baseline in Drinking Risk Level (DRL); for patients at very high risk at Baseline: a shift to medium risk or below, and for patients at high or medium risk at Baseline: a shift to low risk or below. | Month 6 | 
| Change From Baseline in Clinical Status Using CGI-S | The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). | Baseline and Week 24 | 
| Change in Clinical Status Using the CGI-I | The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7- point scale ranging from 1 (very much improved) to 7 (very much worse). | Week 24 | 
| Liver Function Test Gamma-glutamyl Transferase (GGT) | GGT values | Week 24 | 
| Liver Function Test Alanine Aminotransferase (ALAT) | ALAT values | Week 24 | 
| Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs) | Number of HDDs over a month (28 days), where one HDD was defined as a day with alcohol consumption ≥60 g for men and ≥40 g for women. | Baseline and Month 13 | 
| Change From Baseline in the Monthly Total Alcohol Consumption (TAC) | TAC was defined as mean daily alcohol consumption in g/day over a month (28 days). | Baseline and Month 13 | 
| Drinking Risk Level (RSDRL) Response | RSDRL response was defined as a downward shift from baseline in Drinking Risk Level (DRL); for patients at very high risk at Baseline: a shift to medium risk or below, and for patients at high or medium risk at Baseline: a shift to low risk or below. | Month 13 | 
| Change From Baseline in Clinical Status Using CGI-S | The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). | Baseline and Week 52 | 
| Change in Clinical Status Using the CGI-I | The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7- point scale ranging from 1 (very much improved) to 7 (very much worse). | Week 52 | 
| Liver Function Test Gamma-glutamyl Transferase (GGT) | GGT values | Week 52 | 
| Liver Function Test Alanine Aminotransferase (ALAT) | ALAT values | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacologic Actions, Alcohol-Related Disorders, Alcoholism, Mental Disorders, Central Nervous System Agents