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)

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence
• Intervention / Treatment: Drug: Nalmefene hydrochloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 678
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Region, Japan
    • Kanto
  • Region, Japan
    • Kyusyu
  • Region, Japan
    • Chubu
  • Region, Japan
    • Hokkaido
  • Region, Japan
    • Kinki
  • Region, Japan
    • Tohoku
  • Region, Japan
    • Tyugoku

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; As-needed; tablets, orally
EXPERIMENTAL: Nalmefene hydrochloride 10 mg	Drug: Nalmefene hydrochloride; As-needed; tablets, orally
EXPERIMENTAL: Nalmefene hydrochloride 20 mg	Drug: Nalmefene hydrochloride; As-needed; tablets, orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Collaborators: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 9, 2015
• Primary Completion (ACTUAL): July 30, 2016
• Study Completion (ACTUAL): July 30, 2016

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 10, 2015
• First Posted (ESTIMATE): February 18, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 3, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Nalmefene
• Other Study ID Numbers: 339-14-001; JapicCTI-152804 (OTHER: Japic)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No