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 to evaluate the efficacy, safety and tolerability of nalmefene in the treatment of 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 efficacy and safety of as-needed use of nalmefene 18.06 mg versus placebo in decreasing monthly Heavy Drinking Days (HDDs) and decreasing the total consumption during a period of 6 months in adult patients with alcohol dependence.

Official Title
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Nalmefene Efficacy Study I: Randomised, Double-blind, Placebo-controlled, Parallel-group, Efficacy Study of 20 mg 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 HDDs in the 4 weeks preceding the Screening Visit had had an average alcohol consumption at WHO medium risk level or above in the 4 weeks preceding the Screening Visit Exclusion Criteria: The patient: had a DSM-IV Axis I disorder other than alcohol dependence or nicotine dependence had 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 reported current or recent treatment with antipsychotics or antidepressants 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, 6 months<br>|
| Experimental: Nalmefene<br> | Drug: Nalmefene<br>* 18.06 mg, as-needed use, tablets, orally, 6 months. 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 |
| --- | --- | --- |
| 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 | 

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