Safety and Efficacy of Nalmefene in Patients With Alcohol Dependence (SENSE)

• ClinicalTrials.gov Identifier: NCT00811941
• Recruitment Status: Completed
• First Posted: December 19, 2008
• Results First Posted: August 7, 2013
• Last Update Posted: August 7, 2013
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alcohol Dependence	Drug: Placebo; Drug: Nalmefene	Phase 3

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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 665 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: March 2009
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Placebo; as-needed use, tablets, orally, 52 weeks
Experimental: Nalmefene	Drug: Nalmefene; 18.06 mg as-needed use, tablets, orally, 52 weeks. 18.06 mg nalmefene equals 20 mg nalmefene hydrochloride.; Other Name: Selincro™

Outcome Measures

Primary Outcome Measures :

1. Number of Patients With Adverse Events (AEs) [ Time Frame: 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. ]
   Overview of AEs
2. Percentage of Patients Who Withdrew Due to Intolerance to Treatment [ Time Frame: Baseline to Week 52 ]
3. Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs) [ Time Frame: 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.
4. Change From Baseline in the Monthly Total Alcohol Consumption (TAC) [ Time Frame: Baseline and Month 6 ]
   TAC was defined as mean daily alcohol consumption in g/day over a month (28 days).

Secondary Outcome Measures :

1. Drinking Risk Level (RSDRL) Response [ Time Frame: 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.
2. Change From Baseline in Clinical Status Using CGI-S [ Time Frame: 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).
3. Change in Clinical Status Using the CGI-I [ Time Frame: 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).
4. Liver Function Test Gamma-glutamyl Transferase (GGT) [ Time Frame: Week 24 ]
   GGT values
5. Liver Function Test Alanine Aminotransferase (ALAT) [ Time Frame: Week 24 ]
   ALAT values
6. Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs) [ Time Frame: Baseline and Month 13 ]
   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.
7. Change From Baseline in the Monthly Total Alcohol Consumption (TAC) [ Time Frame: Baseline and Month 13 ]
   TAC was defined as mean daily alcohol consumption in g/day over a month (28 days).
8. Drinking Risk Level (RSDRL) Response [ Time Frame: Month 13 ]
   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.
9. Change From Baseline in Clinical Status Using CGI-S [ Time Frame: Baseline and Week 52 ]
   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).
10. Change in Clinical Status Using the CGI-I [ Time Frame: Week 52 ]
    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).
11. Liver Function Test Gamma-glutamyl Transferase (GGT) [ Time Frame: Week 52 ]
    GGT values
12. Liver Function Test Alanine Aminotransferase (ALAT) [ Time Frame: Week 52 ]
    ALAT values

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

  Show 60 Study Locations

Sponsors and Collaborators

H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@lundbeck.com

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Laramée P, Brodtkorb TH, Rahhali N, Knight C, Barbosa C, François C, Toumi M, Daeppen JB, Rehm J. The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model. BMJ Open. 2014 Sep 16;4(9):e005376. doi: 10.1136/bmjopen-2014-005376.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT00811941 History of Changes
• Other Study ID Numbers: 12013A; 2007-002315-92 ( EudraCT Number )
• First Posted: December 19, 2008
• Results First Posted: August 7, 2013
• Last Update Posted: August 7, 2013
• Last Verified: July 2013

Keywords provided by H. Lundbeck A/S:

Pharmacologic Actions; Alcohol-Related Disorders; Alcoholism; Mental Disorders; Central Nervous System Agents

Additional relevant MeSH terms:

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Ethanol; Naltrexone; Nalmefene; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Narcotic Antagonists; Sensory System Agents; Peripheral Nervous System Agents; Alcohol Deterrents