Efficacy of Nalmefene in Patients With Alcohol Dependence

Phase 3

Completed

Brief Summary: The purpose of the study is to evaluate the efficacy, safety and tolerability of nalmefene in the treatment of alcohol dependence.

Detailed Description: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Nalmefene	Nalmefene	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs)	Baseline and Month 6	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.
Change From Baseline in the Monthly Total Alcohol Consumption (TAC)	Baseline and Month 6	TAC was defined as mean daily alcohol consumption in g/day over a month (28 days).

Secondary Outcome Measures

Name	Time	Method
Drinking Risk Level (RSDRL) Response	Month 6	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.
Change From Baseline in Clinical Status Using CGI-S	Baseline and Week 24	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).
Change in Clinical Status Using the CGI-I	Week 24	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).
Liver Function Test Gamma-glutamyl Transferase (GGT)	Week 24	GGT values
Liver Function Test Alanine Aminotransferase (ALAT)	Week 24	ALAT values

Locations (38): AT004
🇦🇹
Salzburg, Austria
FI008
🇫🇮
Helsinki, Finland
DE006
🇩🇪
Hamburg, Germany
AT003
🇦🇹
Wien, Austria
SE005
🇸🇪
Kalmar, Sweden
DE016
🇩🇪
Berlin, Germany
AT001
🇦🇹
Linz, Austria
AT002
🇦🇹
Vienna, Austria
FI009
🇫🇮
Helsinki, Finland
FI007
🇫🇮
Järvenpää, Finland
FI004
🇫🇮
Kuusankoski, Finland
FI015
🇫🇮
Oulu, Finland
FI001
🇫🇮
Mikkeli, Finland
FI003
🇫🇮
Tampere, Finland
FI013
🇫🇮
Kuopio, Finland
FI002
🇫🇮
Tampere, Finland
DE011
🇩🇪
Bad Saarow, Germany
FI014
🇫🇮
Turku, Finland
FI011
🇫🇮
Vantaa, Finland
DE005
🇩🇪
Berlin, Germany
DE002
🇩🇪
Berlin, Germany
DE017
🇩🇪
Berlin, Germany
DE008
🇩🇪
Berlin, Germany
DE019
🇩🇪
Berlin, Germany
DE003
🇩🇪
Mannheim, Germany
DE001
🇩🇪
Hamburg, Germany
DE007
🇩🇪
Leukersdorf, Germany
DE010
🇩🇪
Regensburg, Germany
DE014
🇩🇪
Munich, Germany
DE018
🇩🇪
Siegen, Germany
SE011
🇸🇪
Gothenburg, Sweden
DE020
🇩🇪
Wallerfing, Germany
SE001
🇸🇪
Malmo, Sweden
SE006
🇸🇪
Linköping, Sweden
SE004
🇸🇪
Stockholm, Sweden
SE002
🇸🇪
Stockholm, Sweden
SE008
🇸🇪
Stockholm, Sweden
SE009
🇸🇪
Uppsala, Sweden