Trial Outcomes & Findings for Safety and Efficacy of Nalmefene in Patients With Alcohol Dependence (NCT NCT00811941)

NCT ID: NCT00811941

Last Updated: 2013-08-07

Results Overview

Overview of AEs

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

665 participants

Primary outcome timeframe

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.

Results posted on

2013-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg as-needed use, tablets, orally, 52 weeks
All Randomised Patients STARTED	166	509
All Randomised Patients COMPLETED	164	501
All Randomised Patients NOT COMPLETED	2	8
All Treated Patients STARTED	164	501
All Treated Patients COMPLETED	112	310
All Treated Patients NOT COMPLETED	52	191

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg as-needed use, tablets, orally, 52 weeks
All Randomised Patients Did not receive placebo/nalmefene	2	8
All Treated Patients Adverse Event	2	43
All Treated Patients Lack of Efficacy	2	3
All Treated Patients Non-compliance	1	8
All Treated Patients Protocol Violation	5	17
All Treated Patients Withdrawal by Subject	35	94
All Treated Patients Lost to Follow-up	3	12
All Treated Patients Other Reason	4	14

Baseline Characteristics

Safety and Efficacy of Nalmefene in Patients With Alcohol Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=166 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=509 Participants as-needed use, tablets, orally, 52 weeks	Total n=675 Participants Total of all reporting groups
Age Continuous	44.3 years STANDARD_DEVIATION 12.0 • n=5 Participants	44.3 years STANDARD_DEVIATION 11.2 • n=7 Participants	44.3 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	116 Participants n=7 Participants	155 Participants n=5 Participants
Sex: Female, Male Male	127 Participants n=5 Participants	393 Participants n=7 Participants	520 Participants n=5 Participants
Previously Treated for Alcohol Dependence NO	105 participants n=5 Participants	338 participants n=7 Participants	443 participants n=5 Participants
Previously Treated for Alcohol Dependence YES	61 participants n=5 Participants	171 participants n=7 Participants	232 participants n=5 Participants
Previously Treated for Alcohol Withdrawal Symptoms NO	118 participants n=5 Participants	372 participants n=7 Participants	490 participants n=5 Participants
Previously Treated for Alcohol Withdrawal Symptoms YES	48 participants n=5 Participants	137 participants n=7 Participants	185 participants n=5 Participants
Total Monthly Heavy Drinking Days (HDD)	13.69 days STANDARD_DEVIATION 6.03 • n=5 Participants	14.08 days STANDARD_DEVIATION 6.22 • n=7 Participants	13.98 days STANDARD_DEVIATION 6.17 • n=5 Participants
Total Alcohol Consumption (TAC) g Alcohol/Day	68.00 g STANDARD_DEVIATION 40.62 • n=5 Participants	68.64 g STANDARD_DEVIATION 39.98 • n=7 Participants	68.49 g STANDARD_DEVIATION 40.11 • 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	26 participants n=5 Participants	79 participants n=7 Participants	105 participants n=5 Participants
Drinking Risk Level (DRL) MEDIUM	49 participants n=5 Participants	167 participants n=7 Participants	216 participants n=5 Participants
Drinking Risk Level (DRL) HIGH	59 participants n=5 Participants	148 participants n=7 Participants	207 participants n=5 Participants
Drinking Risk Level (DRL) VERY HIGH	32 participants n=5 Participants	114 participants n=7 Participants	146 participants n=5 Participants
Clinical Global Impression - Severity of Illness (CGI-S)	3.88 units on a scale STANDARD_DEVIATION 1.03 • n=5 Participants	3.95 units on a scale STANDARD_DEVIATION 1.12 • n=7 Participants	3.94 units on a scale STANDARD_DEVIATION 1.09 • n=5 Participants
Gamma-glutamyl Transferase (GGT)	71.03 international units per liter (IU/L) STANDARD_DEVIATION 116.25 • n=5 Participants	68.82 international units per liter (IU/L) STANDARD_DEVIATION 109.87 • n=7 Participants	69.36 international units per liter (IU/L) STANDARD_DEVIATION 111.39 • n=5 Participants
Alanine Aminotransferase (ALAT)	31.46 IU/L STANDARD_DEVIATION 20.20 • n=5 Participants	33.87 IU/L STANDARD_DEVIATION 22.61 • n=7 Participants	33.28 IU/L STANDARD_DEVIATION 22.05 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: All-patients-treated set (APTS) - all patients in the APRS excluding those with no recorded investigational medicinal product (IMP) intake and all IMP returned

Overview of AEs

Outcome measures

Outcome measures
Measure	Placebo n=164 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=501 Participants as-needed use, tablets, orally, 52 weeks
Number of Patients With Adverse Events (AEs) Patients with AEs Leading to Withdrawal	5 participants	57 participants
Number of Patients With Adverse Events (AEs) Patients with AEs	103 participants	377 participants
Number of Patients With Adverse Events (AEs) Patients with Serious AEs (SAEs)	8 participants	35 participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: All-patients-treated Set (APTS)

Outcome measures

Outcome measures
Measure	Placebo n=164 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=501 Participants as-needed use, tablets, orally, 52 weeks
Percentage of Patients Who Withdrew Due to Intolerance to Treatment	1.2 percentage of participants	8.6 percentage of participants

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: Full-analysis set (FAS) - all patients in the 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=110 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=320 Participants as-needed use, tablets, orally, 52 weeks
Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs)	-8.92 days Standard Error 0.56	-9.80 days Standard Error 0.35

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=110 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=320 Participants as-needed use, tablets, orally, 52 weeks
Change From Baseline in the Monthly Total Alcohol Consumption (TAC)	-45.58 g Standard Error 2.61	-49.05 g Standard Error 1.64

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=137 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=415 Participants as-needed use, tablets, orally, 52 weeks
Drinking Risk Level (RSDRL) Response	63.5 percentage of participants	62.2 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=104 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=306 Participants as-needed use, tablets, orally, 52 weeks
Change From Baseline in Clinical Status Using CGI-S	-0.75 units on a scale Standard Error 0.08	-0.94 units on a scale Standard Error 0.05

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=104 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=306 Participants as-needed use, tablets, orally, 52 weeks
Change in Clinical Status Using the CGI-I	2.68 units on a scale Standard Error 0.10	2.54 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 24

Population: FAS

GGT values

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=319 Participants as-needed use, tablets, orally, 52 weeks
Liver Function Test Gamma-glutamyl Transferase (GGT)	34.5 IU/L Geometric Coefficient of Variation 63.5	32.2 IU/L Geometric Coefficient of Variation 71.1

SECONDARY outcome

Timeframe: Week 24

Population: FAS

ALAT values

Outcome measures

Outcome measures
Measure	Placebo n=108 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=318 Participants as-needed use, tablets, orally, 52 weeks
Liver Function Test Alanine Aminotransferase (ALAT)	25.8 IU/L Geometric Coefficient of Variation 52.4	25.6 IU/L Geometric Coefficient of Variation 56.7

SECONDARY outcome

Timeframe: Baseline and Month 13

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=258 Participants as-needed use, tablets, orally, 52 weeks
Change From Baseline in the Monthly Number of Heavy Drinking Days (HDDs)	-8.96 days Standard Error 0.58	-10.53 days Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline and Month 13

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=97 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=258 Participants as-needed use, tablets, orally, 52 weeks
Change From Baseline in the Monthly Total Alcohol Consumption (TAC)	-46.33 g Standard Error 2.73	-52.80 g Standard Error 1.76

SECONDARY outcome

Timeframe: Month 13

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=137 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=415 Participants as-needed use, tablets, orally, 52 weeks
Drinking Risk Level (RSDRL) Response	54.0 percentage of participants	54.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=258 Participants as-needed use, tablets, orally, 52 weeks
Change From Baseline in Clinical Status Using CGI-S	-1.08 units on a scale Standard Error 0.10	-1.30 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 52

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=258 Participants as-needed use, tablets, orally, 52 weeks
Change in Clinical Status Using the CGI-I	2.52 units on a scale Standard Error 0.10	2.26 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Week 52

Population: FAS

GGT values

Outcome measures

Outcome measures
Measure	Placebo n=98 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=259 Participants as-needed use, tablets, orally, 52 weeks
Liver Function Test Gamma-glutamyl Transferase (GGT)	41.3 IU/L Geometric Coefficient of Variation 76.2	32.0 IU/L Geometric Coefficient of Variation 80.6

SECONDARY outcome

Timeframe: Week 52

Population: FAS

ALAT values

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=259 Participants as-needed use, tablets, orally, 52 weeks
Liver Function Test Alanine Aminotransferase (ALAT)	27.8 IU/L Geometric Coefficient of Variation 55.6	24.6 IU/L Geometric Coefficient of Variation 58.5

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 57 other events

Deaths: 0 deaths

Nalmefene 18.06 mg

Serious events: 35 serious events

Other events: 273 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=164 participants at risk as-needed use, tablets, orally, 52 weeks	Nalmefene 18.06 mg n=501 participants at risk as-needed use, tablets, orally, 52 weeks
Gastrointestinal disorders Nausea	5.5% 9/164 • 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.	22.4% 112/501 • 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.
Gastrointestinal disorders Vomiting	1.2% 2/164 • 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.	11.4% 57/501 • 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.
General disorders Fatigue	1.8% 3/164 • 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.	5.4% 27/501 • 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.
Infections and infestations Nasopharyngitis	11.6% 19/164 • 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.	10.8% 54/501 • 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.
Injury, poisoning and procedural complications Accidental overdose	5.5% 9/164 • 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.	1.8% 9/501 • 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.
Injury, poisoning and procedural complications Fall	6.7% 11/164 • 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.	1.00% 5/501 • 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.
Nervous system disorders Dizziness	3.7% 6/164 • 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.	14.6% 73/501 • 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.
Nervous system disorders Headache	7.9% 13/164 • 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.	12.2% 61/501 • 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.
Nervous system disorders Somnolence	4.9% 8/164 • 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.	8.4% 42/501 • 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.
Psychiatric disorders Insomnia	6.7% 11/164 • 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.	14.6% 73/501 • 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.

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