Alcohol Dependence
Conditions
Brief summary
The long-term safety and efficacy of nalmefene hydrochloride at 20 mg in patients with alcohol dependence will be evaluated in a multicenter, open-label, uncontrolled trial.
Interventions
Sponsors
H. Lundbeck A/S
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have completed Study 339-14-001 * Patients who have signed the informed consent form for Study 339-14-002
Exclusion criteria
* The patient has a clinically significant unstable illness (eg, complication of New York Heart Association (NYHA) class III or IV heart failure or angina pectoris, renal function disorder with estimated glomerular filtration rate (eGFR) of \< 30 mL/min/1.73 m2, hepatic failure, and neoplastic disorder) * The patient has a clinically significant abnormal electrocardiogram (ECG) which is inappropriate for the participation in the trial in the opinion of the investigator or subinvestigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events | 24-week treatment period |
Secondary
| Measure | Time frame |
|---|---|
| Change in the Number of Heavy Drinking Days (HDDs) From Baseline | Week 24 |
| Change in Total Alcohol Consumption (TAC) From Baseline | Week 24 |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nalmefene 20 mg in the lead-in Study Patients who completed the treatment (nalmefene hydrochloride 20 mg) in the lead-in study were eligible for the extension study. In the extension study, all patients were received nalmefene 20 mg tablets, as-needed, orally, 24-week treatment period. | 137 |
| Nalmefene 10 mg in the lead-in Study Patients who completed the treatment (nalmefene hydrochloride 10 mg) in the lead-in study were eligible for the extension study. In the extension study, all patients were received nalmefene 20 mg tablets, as-needed, orally, 24-week treatment period. | 94 |
| Placebo in the lead-in Study Patients who completed the treatment (placebo) in the lead-in study were eligible for the extension study. In the extension study, all patients were received nalmefene 20 mg tablets, as-needed, orally, 24-week treatment period. | 172 |
| Total | 403 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 2 | 32 |
| Overall Study | Physician Decision | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 8 | 5 |
Baseline characteristics
| Characteristic | Nalmefene 20 mg in the lead-in Study | Total | Placebo in the lead-in Study | Nalmefene 10 mg in the lead-in Study |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 44 Participants | 18 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 120 Participants | 359 Participants | 154 Participants | 85 Participants |
| Age, Customized | 50.0 years STANDARD_DEVIATION 11.7 | 49.4 years STANDARD_DEVIATION 11.2 | 48.5 years STANDARD_DEVIATION 11 | 50.1 years STANDARD_DEVIATION 11 |
| Heavy Drinking Days (HDDs) | 22.54 days/month STANDARD_DEVIATION 6.7 | 23.04 days/month STANDARD_DEVIATION 6.32 | 22.70 days/month STANDARD_DEVIATION 6.54 | 24.38 days/month STANDARD_DEVIATION 5.1 |
| Race/Ethnicity, Customized Japanese | 137 Participants | 403 Participants | 172 Participants | 94 Participants |
| Region of Enrollment Japan | 137 Participants | 403 Participants | 172 Participants | 94 Participants |
| Sex: Female, Male Female | 33 Participants | 116 Participants | 64 Participants | 19 Participants |
| Sex: Female, Male Male | 104 Participants | 287 Participants | 108 Participants | 75 Participants |
| Total Alcohol Consumption (TAC) | 94.10 g/day STANDARD_DEVIATION 34.43 | 93.35 g/day STANDARD_DEVIATION 36.9 | 92.30 g/day STANDARD_DEVIATION 41.03 | 94.16 g/day STANDARD_DEVIATION 32.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 403 |
| other Total, other adverse events | 209 / 403 |
| serious Total, serious adverse events | 3 / 403 |
Outcome results
Primary
Number of Participants With Adverse Events
Time frame: 24-week treatment period
Population: Safety analysis set, which included all patients who received at least one dose of study medication during the 24-week treatment period in the extension study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene 20 mg in the lead-in Study | Number of Participants With Adverse Events | 96 Number of participants |
| Nalmefene 10 mg in the lead-in Study | Number of Participants With Adverse Events | 67 Number of participants |
| Placebo in the lead-in Study | Number of Participants With Adverse Events | 141 Number of participants |
Secondary
Change in the Number of Heavy Drinking Days (HDDs) From Baseline
Time frame: Week 24
Population: Full analysis set, which included all patients from the SS who had data available for HDDs at baseline in the lead-in study and at one or more time-points in the extension study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene 20 mg in the lead-in Study | Change in the Number of Heavy Drinking Days (HDDs) From Baseline | -15.09 days/month | Standard Error 0.77 |
| Nalmefene 10 mg in the lead-in Study | Change in the Number of Heavy Drinking Days (HDDs) From Baseline | -17.15 days/month | Standard Error 0.94 |
| Placebo in the lead-in Study | Change in the Number of Heavy Drinking Days (HDDs) From Baseline | -16.35 days/month | Standard Error 0.7 |
Secondary
Change in Total Alcohol Consumption (TAC) From Baseline
Time frame: Week 24
Population: Full analysis set, which included all patients from the SS who had data available for HDDs at baseline in the lead-in study and at one or more time-points in the extension study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene 20 mg in the lead-in Study | Change in Total Alcohol Consumption (TAC) From Baseline | -53.20 g/day | Standard Error 2.29 |
| Nalmefene 10 mg in the lead-in Study | Change in Total Alcohol Consumption (TAC) From Baseline | -57.93 g/day | Standard Error 2.77 |
| Placebo in the lead-in Study | Change in Total Alcohol Consumption (TAC) From Baseline | -55.77 g/day | Standard Error 2.06 |