Trial Outcomes & Findings for Efficacy of Nalmefene in Patients With Alcohol Dependence (NCT NCT00811720)

Last Updated: 2013-07-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

598 participants

Primary outcome timeframe

Baseline and Month 6

Results posted on

2013-07-09

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg as-needed use, tablets, orally, 6 months
All Randomised Patients STARTED	298	306
All Randomised Patients COMPLETED	296	302
All Randomised Patients NOT COMPLETED	2	4
All Treated Patients STARTED	296	302
All Treated Patients COMPLETED	200	138
All Treated Patients NOT COMPLETED	96	164

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg as-needed use, tablets, orally, 6 months
All Randomised Patients Did not receive placebo/nalmefene	2	4
All Treated Patients Adverse Event	20	62
All Treated Patients Lack of Efficacy	22	18
All Treated Patients Non-compliance	0	14
All Treated Patients Protocol Violation	9	16
All Treated Patients Withdrawal by Subject	28	34
All Treated Patients Lost to Follow-up	10	16
All Treated Patients Other Reason	7	4

Baseline Characteristics

Efficacy of Nalmefene in Patients With Alcohol Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=298 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=306 Participants as-needed use, tablets, orally, 6 months	Total n=604 Participants Total of all reporting groups
Age Continuous	52.1 years STANDARD_DEVIATION 9.1 • n=5 Participants	51.0 years STANDARD_DEVIATION 10.1 • n=7 Participants	51.6 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	102 Participants n=7 Participants	198 Participants n=5 Participants
Sex: Female, Male Male	202 Participants n=5 Participants	204 Participants n=7 Participants	406 Participants n=5 Participants
Previously Treated for Alcohol Dependence NO	209 participants n=5 Participants	215 participants n=7 Participants	424 participants n=5 Participants
Previously Treated for Alcohol Dependence YES	89 participants n=5 Participants	91 participants n=7 Participants	180 participants n=5 Participants
Previously Treated for Alcohol Withdrawal Symptoms NO	245 participants n=5 Participants	246 participants n=7 Participants	491 participants n=5 Participants
Previously Treated for Alcohol Withdrawal Symptoms YES	53 participants n=5 Participants	60 participants n=7 Participants	113 participants n=5 Participants
Total Monthly Heavy Drinking Days (HDD)	19.53 days STANDARD_DEVIATION 6.96 • n=5 Participants	19.51 days STANDARD_DEVIATION 7.29 • n=7 Participants	19.52 days STANDARD_DEVIATION 7.12 • n=5 Participants
Total Alcohol Consumption (TAC) g Alcohol/Day	84.11 g STANDARD_DEVIATION 41.49 • n=5 Participants	84.79 g STANDARD_DEVIATION 42.07 • n=7 Participants	84.45 g STANDARD_DEVIATION 41.75 • n=5 Participants
Drinking Risk Level (DRL) Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Drinking Risk Level (DRL) Low	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Drinking Risk Level (DRL) Medium	60 participants n=5 Participants	68 participants n=7 Participants	128 participants n=5 Participants
Drinking Risk Level (DRL) High	119 participants n=5 Participants	114 participants n=7 Participants	233 participants n=5 Participants
Drinking Risk Level (DRL) Very High	117 participants n=5 Participants	122 participants n=7 Participants	239 participants n=5 Participants
Clinical Global Impression - Severity of Illness (CGI-S)	3.96 units on a scale STANDARD_DEVIATION 1.52 • n=5 Participants	4.02 units on a scale STANDARD_DEVIATION 1.48 • n=7 Participants	3.99 units on a scale STANDARD_DEVIATION 1.50 • n=5 Participants
Gamma-glutamyl Transferase (GGT)	83.55 international units per liter (IU/L) STANDARD_DEVIATION 90.83 • n=5 Participants	80.29 international units per liter (IU/L) STANDARD_DEVIATION 103.51 • n=7 Participants	81.90 international units per liter (IU/L) STANDARD_DEVIATION 97.39 • n=5 Participants
Alanine Aminotransferase (ALAT)	34.13 IU/L STANDARD_DEVIATION 21.77 • n=5 Participants	33.15 IU/L STANDARD_DEVIATION 18.09 • n=7 Participants	33.63 IU/L STANDARD_DEVIATION 19.98 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: Full-analysis set (FAS) - all patients in the all-patients-treated set (APTS) who had at least one valid post-baseline assessment in the main treatment period of both co-primary efficacy variables (HDD and TAC) and had an average alcohol consumption at medium Drinking Risk Level (DRL) or above according to WHO criteria at Baseline.

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.

Outcome measures

Outcome measures
Measure	Placebo n=213 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=152 Participants as-needed use, tablets, orally, 6 months
Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs)	-8.91 days Standard Error 0.56	-11.24 days Standard Error 0.60

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: FAS

TAC was defined as mean daily alcohol consumption in g/day over a month (28 days).

Outcome measures

Outcome measures
Measure	Placebo n=213 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=152 Participants as-needed use, tablets, orally, 6 months
Change From Baseline in the Monthly Total Alcohol Consumption (TAC)	-39.70 g Standard Error 2.25	-50.66 g Standard Error 2.41

SECONDARY outcome

Timeframe: Month 6

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=289 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=290 Participants as-needed use, tablets, orally, 6 months
Drinking Risk Level (RSDRL) Response	44.3 percentage of participants	36.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: FAS

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).

Outcome measures

Outcome measures
Measure	Placebo n=210 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=152 Participants as-needed use, tablets, orally, 6 months
Change From Baseline in Clinical Status Using CGI-S	-0.90 units on a scale Standard Error 0.08	-1.27 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Week 24

Population: FAS

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).

Outcome measures

Outcome measures
Measure	Placebo n=210 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=152 Participants as-needed use, tablets, orally, 6 months
Change in Clinical Status Using the CGI-I	2.65 units on a scale Standard Error 0.07	2.30 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Week 24

Population: FAS

GGT values

Outcome measures

Outcome measures
Measure	Placebo n=211 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=158 Participants as-needed use, tablets, orally, 6 months
Liver Function Test Gamma-glutamyl Transferase (GGT)	45.7 IU/L Geometric Coefficient of Variation 56.2 • Interval 0.8 to 0.97	40.3 IU/L Geometric Coefficient of Variation 52.5

SECONDARY outcome

Timeframe: Week 24

Population: FAS

ALAT values

Outcome measures

Outcome measures
Measure	Placebo n=209 Participants as-needed use, tablets, orally, 6 months	Nalmefene 18.06 mg n=158 Participants as-needed use, tablets, orally, 6 months
Liver Function Test Alanine Aminotransferase (ALAT)	28.1 IU/L Geometric Coefficient of Variation 44.7 • Interval 0.84 to 0.98	25.4 IU/L Geometric Coefficient of Variation 42.6

Adverse Events

Placebo

Serious events: 18 serious events

Other events: 113 other events

Deaths: 0 deaths

Nalmefene 18.06 mg

Serious events: 17 serious events

Other events: 191 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=296 participants at risk	Nalmefene 18.06 mg n=302 participants at risk
Gastrointestinal disorders Nausea	6.1% 18/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	27.5% 83/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Gastrointestinal disorders Vomiting	2.7% 8/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	7.9% 24/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
General disorders Fatigue	8.4% 25/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	17.5% 53/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Infections and infestations Nasopharyngitis	13.2% 39/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	11.9% 36/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Nervous system disorders Dizziness	7.8% 23/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	27.8% 84/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Nervous system disorders Headache	9.1% 27/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	11.9% 36/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Psychiatric disorders Insomnia	3.4% 10/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	10.3% 31/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Psychiatric disorders Sleep disorder	0.34% 1/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	10.6% 32/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.7% 5/296 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.	5.3% 16/302 • Serious Adverse Events: 24 weeks, a 4-week run-out period, 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: 24 weeks and a 4-week run-out period.

Additional Information

H. Lundbeck A/S

Phone: +45 3630 1311

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The main publication has to be published before any sub publication. The investigators shall obtain Lundbeck's written approval before publishing any publication relating to nalmefene, the Study, the Protocol and/or the results recorded during the Study.
Publication restrictions are in place

Restriction type: OTHER