A Multicenter, Randomized, Double-blind, Placebo-controlled, 3-parallel-group Comparison Trial to Investigate the Effect of Nalmefene on Alcohol Consumption Reduction in Patients With Alcohol Dependence (Phase 3 Trial)

Study Overview
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Brief Summary
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The efficacy, safety, and dose-response of nalmefene hydrochloride at 10 mg and 20 mg in patients with alcohol dependence will be evaluated in a multicenter, randomized, double-blind, placebo-controlled, 3-parallel-group comparative trial. The superiority of nalmefene hydrochloride at 20 mg to placebo will be verified in terms of reduction of alcohol consumption.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, 3-parallel-group Comparison Trial to Investigate the Effect of Nalmefene on Alcohol Consumption Reduction in Patients With Alcohol Dependence (Phase 3 Trial)

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: Nalmefene hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese males and females aged 20 or above who have signed the informed consent form The patient has alcohol dependence, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) and confirmed by Mini-international Neuropsychiatric Interview (M. I. N. I.) The patient has a drinking risk level of High or above (> 60 g for men and > 40 g for women) both at the Screening Visit and at the Randomization Visit . Exclusion Criteria: The patient with a current diagnosis or history of substance use disorders (except for alcohol, nicotine, and caffeine), according to DSM-IV-TR and confirmed by M. I. N. I. The patient has reported current use of, or has tested positive for, drugs of abuse (opiates, methadone, cocaine, amphetamines, barbiturates) at the screening test

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| Experimental: Nalmefene hydrochloride 10 mg<br> | Drug: Nalmefene hydrochloride<br>* As-needed; tablets, orally<br>|
| Experimental: Nalmefene hydrochloride 20 mg<br> | Drug: Nalmefene hydrochloride<br>* As-needed; tablets, orally<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* As-needed; tablets, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 12 | The number of HDDs is defined as the number of days per month [days/month] with alcohol consumption of > 60 g for males and > 40 g for females | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24 |  | Week 24 | 
| Change in Total Alcohol Consumption (TAC) From Baseline at Week 12 |  | Week 12 | 
| Change in Total Alcohol Consumption (TAC) From Baseline at Week 24 |  | Week 24 | 
| Response Shift Drinking Risk Level (RSDRL) at Week 12 | Proportion of patients with a downward shift in drinking risk level of two categories or more | Week 12 | 
| Response Shift Drinking Risk Level (RSDRL) at Week 24 | Proportion of patients with a downward shift in drinking risk level of two categories or more | Week 24 | 
| Response Low Drinking Risk Level (RLDRL) at Week 12 | Proportion of patients with low or lower drinking risk level | Week 12 | 
| Response Low Drinking Risk Level (RLDRL) at Week 24 | Proportion of patients with low or lower drinking risk level | Week 24 | 
| 70% TAC Responder Rate at Week 12 | Proportion of patients with a 70% decrease in TAC | Week 12 | 
| 70% TAC Responder Rate at Week 24 | Proportion of patients with a 70% decrease in TAC | Week 24 | 
| HDD Responder Rate at Week 12 | Proportion of patients with ≤4 HDDs | Week 12 | 
| HDD Responder Rate at Week 24 | Proportion of patients with ≤4 HDDs | Week 24 | 
| Change in CGI-S From Baseline at Week 12 | The CGI-S scale was used by clinicians when assessing their global impression of a patient's current clinical condition. The investigator or subinvestigator used his/her clinical experience with this patient population to rate the severity of a subject's clinical condition on a 7-point scale ranging from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). | Week 12 | 
| Change in CGI-S From Baseline at Week 24 | The CGI-S scale was used by clinicians when assessing their global impression of a patient's current clinical condition. The investigator or subinvestigator used his/her clinical experience with this patient population to rate the severity of a subject's clinical condition on a 7-point scale ranging from 1 (Normal, not at all ill) to 7 (Among the most extremely ill patients). | Week 24 | 
| Change in CGI-I From Baseline at Week 12 | The CGI-I scale is used to assess a patient's improvement (or worsening). The investigator or subinvestigator assesses a subject's condition relative to baseline on a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse). | Week 12 | 
| Change in CGI-I From Baseline at Week 24 | The CGI-I scale was used to assess a patient's improvement (or worsening). The investigator or subinvestigator assesses a subject's condition relative to baseline on a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse). | Week 24 | 
| Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12 | All-patients-randomised set | Week 12 | 
| Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24 | All-patients-randomised set | Week 24 | 
| Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12 | All-patients-randomised set | Week 12 | 
| Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24 | All-patients-randomised set | Week 24 |