Alcohol Dependence
Conditions
Brief summary
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.
Interventions
As-needed; tablets, orally
DRUGPlacebo
As-needed; tablets, orally
Sponsors
H. Lundbeck A/S
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 12 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 12 | Proportion of patients with a downward shift in drinking risk level of two categories or more |
| Response Shift Drinking Risk Level (RSDRL) at Week 24 | Week 24 | Proportion of patients with a downward shift in drinking risk level of two categories or more |
| Response Low Drinking Risk Level (RLDRL) at Week 12 | Week 12 | Proportion of patients with low or lower drinking risk level |
| Response Low Drinking Risk Level (RLDRL) at Week 24 | Week 24 | Proportion of patients with low or lower drinking risk level |
| 70% TAC Responder Rate at Week 12 | Week 12 | Proportion of patients with a 70% decrease in TAC |
| 70% TAC Responder Rate at Week 24 | Week 24 | Proportion of patients with a 70% decrease in TAC |
| HDD Responder Rate at Week 12 | Week 12 | Proportion of patients with ≤4 HDDs |
| Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24 | Week 24 | — |
| Change in CGI-S From Baseline at Week 12 | 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). |
| Change in CGI-S From Baseline at Week 24 | 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). |
| Change in CGI-I From Baseline at Week 12 | 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). |
| Change in CGI-I From Baseline at Week 24 | 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). |
| Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12 | Week 12 | All-patients-randomised set |
| Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24 | Week 24 | All-patients-randomised set |
| Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12 | Week 12 | All-patients-randomised set |
| Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24 | Week 24 | All-patients-randomised set |
| HDD Responder Rate at Week 24 | Week 24 | Proportion of patients with ≤4 HDDs |
Countries
Japan
Participant flow
Recruitment details
Safety analysis set, which included all randomized patients who received ≥1 dose of the study medication.
Participants by arm
| Arm | Count |
|---|---|
| Nalmefene Hydrochloride 20 mg Nalmefene hydrochloride: As-needed; tablets, orally | 242 |
| Nalmefene Hydrochloride 10 mg Nalmefene hydrochloride: As-needed; tablets, orally | 180 |
| Placebo Placebo: As-needed; tablets, orally | 244 |
| Total | 666 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 45 | 33 | 11 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Physician Decision | 3 | 2 | 5 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 8 | 9 |
Baseline characteristics
| Characteristic | Nalmefene Hydrochloride 20 mg | Nalmefene Hydrochloride 10 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 21 Participants | 27 Participants | 77 Participants |
| Age, Categorical Between 18 and 65 years | 213 Participants | 159 Participants | 217 Participants | 589 Participants |
| Age, Continuous | 48.9 years STANDARD_DEVIATION 12.2 | 49.2 years STANDARD_DEVIATION 11.9 | 48.1 years STANDARD_DEVIATION 11.4 | 48.7 years STANDARD_DEVIATION 11.8 |
| Clinical Global Impression - Severity of Illness (CGI-S) score | 3.38 units on a scale STANDARD_DEVIATION 1.06 | 3.48 units on a scale STANDARD_DEVIATION 1.15 | 3.45 units on a scale STANDARD_DEVIATION 1.09 | 3.43 units on a scale STANDARD_DEVIATION 1.09 |
| Drinking Risk Level (DRL) High | 135 Participants | 93 Participants | 127 Participants | 355 Participants |
| Drinking Risk Level (DRL) Low | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Drinking Risk Level (DRL) Medium | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Drinking Risk Level (DRL) Very high | 107 Participants | 87 Participants | 116 Participants | 310 Participants |
| Heavy Drinking Days (HDDs) | 22.64 days/month STANDARD_DEVIATION 6.37 | 23.49 days/month STANDARD_DEVIATION 6.07 | 22.97 days/month STANDARD_DEVIATION 6.44 | 22.99 days/month STANDARD_DEVIATION 6.32 |
| Region of Enrollment Japan | 242 participants | 180 participants | 244 participants | 666 participants |
| Serum alanine aminotransferase (ALT) | 24.3 IU/L STANDARD_DEVIATION 14.2 | 24.5 IU/L STANDARD_DEVIATION 14.9 | 23.3 IU/L STANDARD_DEVIATION 14.8 | 24.0 IU/L STANDARD_DEVIATION 14.6 |
| Serum gamma-glutamyltransferase (γ-GT) | 84.7 IU/L STANDARD_DEVIATION 105.4 | 80.7 IU/L STANDARD_DEVIATION 103.8 | 70.7 IU/L STANDARD_DEVIATION 78.7 | 78.5 IU/L STANDARD_DEVIATION 96.1 |
| Sex: Female, Male Female | 72 Participants | 46 Participants | 90 Participants | 208 Participants |
| Sex: Female, Male Male | 170 Participants | 134 Participants | 154 Participants | 458 Participants |
| Total Alcohol Consumption (TAC) | 93.07 g/day STANDARD_DEVIATION 37.45 | 95.93 g/day STANDARD_DEVIATION 41.1 | 95.08 g/day STANDARD_DEVIATION 48.7 | 94.58 g/day STANDARD_DEVIATION 42.79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 248 | 1 / 184 | 0 / 245 |
| other Total, other adverse events | 175 / 248 | 125 / 184 | 127 / 245 |
| serious Total, serious adverse events | 2 / 248 | 2 / 184 | 2 / 245 |
Outcome results
Primary
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
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 12 | -12.25 days/month | Standard Error 0.64 |
| Nalmefene Hydrochloride 10 mg | Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 12 | -12.09 days/month | Standard Error 0.74 |
| Placebo | Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 12 | -7.91 days/month | Standard Error 0.61 |
p-value: 0.000195% CI: [-6.05, -2.62]Mixed Models Analysis
p-value: 0.000195% CI: [-6.05, -2.32]Mixed Models Analysis
Secondary
70% TAC Responder Rate at Week 12
Proportion of patients with a 70% decrease in TAC
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | 70% TAC Responder Rate at Week 12 | 18.0 percentage |
| Nalmefene Hydrochloride 10 mg | 70% TAC Responder Rate at Week 12 | 19.5 percentage |
| Placebo | 70% TAC Responder Rate at Week 12 | 8.5 percentage |
p-value: 0.002295% CI: [3.5, 16.3]Cochran-Mantel-Haenszel
p-value: 0.001695% CI: [3.8, 18.3]Cochran-Mantel-Haenszel
Secondary
70% TAC Responder Rate at Week 24
Proportion of patients with a 70% decrease in TAC
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | 70% TAC Responder Rate at Week 24 | 23.8 percentage |
| Nalmefene Hydrochloride 10 mg | 70% TAC Responder Rate at Week 24 | 23.4 percentage |
| Placebo | 70% TAC Responder Rate at Week 24 | 10.8 percentage |
p-value: 0.000395% CI: [6.2, 20.9]Cochran-Mantel-Haenszel
p-value: 0.001395% CI: [4.6, 21]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in CGI-I From Baseline at Week 12 | 2.62 units on a scale | Standard Error 0.07 |
| Nalmefene Hydrochloride 10 mg | Change in CGI-I From Baseline at Week 12 | 2.65 units on a scale | Standard Error 0.08 |
| Placebo | Change in CGI-I From Baseline at Week 12 | 3.13 units on a scale | Standard Error 0.06 |
p-value: <0.000195% CI: [-0.69, -0.33]Mixed Models Analysis
p-value: <0.000195% CI: [-0.67, -0.27]Mixed Models Analysis
Secondary
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).
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in CGI-I From Baseline at Week 24 | 2.49 units on a scale | Standard Error 0.07 |
| Nalmefene Hydrochloride 10 mg | Change in CGI-I From Baseline at Week 24 | 2.44 units on a scale | Standard Error 0.09 |
| Placebo | Change in CGI-I From Baseline at Week 24 | 2.99 units on a scale | Standard Error 0.07 |
p-value: <0.000195% CI: [-0.7, -0.31]Mixed Models Analysis
p-value: <0.000195% CI: [-0.77, -0.33]Mixed Models Analysis
Secondary
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).
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in CGI-S From Baseline at Week 12 | -0.60 units on a scale | Standard Error 0.05 |
| Nalmefene Hydrochloride 10 mg | Change in CGI-S From Baseline at Week 12 | -0.63 units on a scale | Standard Error 0.06 |
| Placebo | Change in CGI-S From Baseline at Week 12 | -0.34 units on a scale | Standard Error 0.05 |
p-value: 0.000295% CI: [-0.4, -0.13]Mixed Models Analysis
p-value: 0.000195% CI: [-0.45, -0.15]Mixed Models Analysis
Secondary
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).
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in CGI-S From Baseline at Week 24 | -0.75 units on a scale | Standard Error 0.06 |
| Nalmefene Hydrochloride 10 mg | Change in CGI-S From Baseline at Week 24 | -0.77 units on a scale | Standard Error 0.07 |
| Placebo | Change in CGI-S From Baseline at Week 24 | -0.41 units on a scale | Standard Error 0.05 |
p-value: <0.000195% CI: [-0.48, -0.18]Mixed Models Analysis
p-value: <0.000195% CI: [-0.51, -0.19]Mixed Models Analysis
Secondary
Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12
All-patients-randomised set
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12 | 2.968 IU/L | Standard Error 0.023 |
| Nalmefene Hydrochloride 10 mg | Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12 | 2.988 IU/L | Standard Error 0.027 |
| Placebo | Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 12 | 3.038 IU/L | Standard Error 0.021 |
p-value: 0.023495% CI: [-0.13, -0.009]Mixed Models Analysis
Comparison: Mixed model for repeated measures (MMRM) with fixed effect of treatment, sex, time point, treatment-by-time point interaction, logarithm scale baseline value, and logarithm scale baseline value-by-time point interaction with an unstructured variance-covariance matrix structure was used.p-value: 0.137495% CI: [-0.115, 0.016]Mixed Models Analysis
Secondary
Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24
All-patients-randomised set
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24 | 2.971 IU/L | Standard Error 0.023 |
| Nalmefene Hydrochloride 10 mg | Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24 | 2.987 IU/L | Standard Error 0.027 |
| Placebo | Change in Logarithm Scale in Serum Alanine Aminotransferase From Baseline at Week 24 | 3.036 IU/L | Standard Error 0.021 |
p-value: 0.034895% CI: [-0.127, -0.005]Mixed Models Analysis
p-value: 0.144495% CI: [-0.116, 0.017]Mixed Models Analysis
Secondary
Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12
All-patients-randomised set
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12 | 3.666 IU/L | Standard Error 0.027 |
| Nalmefene Hydrochloride 10 mg | Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12 | 3.702 IU/L | Standard Error 0.031 |
| Placebo | Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 12 | 3.858 IU/L | Standard Error 0.025 |
p-value: <0.000195% CI: [-0.262, -0.121]Mixed Models Analysis
p-value: 0.000195% CI: [-0.232, -0.08]Mixed Models Analysis
Secondary
Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24
All-patients-randomised set
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24 | 3.663 IU/L | Standard Error 0.031 |
| Nalmefene Hydrochloride 10 mg | Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24 | 3.692 IU/L | Standard Error 0.035 |
| Placebo | Change in Logarithm Scale in Serum γ-glutamyltransferase From Baseline at Week 24 | 3.831 IU/L | Standard Error 0.028 |
p-value: <0.000195% CI: [-0.248, -0.088]Mixed Models Analysis
p-value: 0.001795% CI: [-0.226, -0.052]Mixed Models Analysis
Secondary
Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24 | -13.25 days/month | Standard Error 0.66 |
| Nalmefene Hydrochloride 10 mg | Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24 | -13.88 days/month | Standard Error 0.77 |
| Placebo | Change in the Number of Heavy Drinking Days (HDDs) From Baseline at Week 24 | -9.33 days/month | Standard Error 0.63 |
p-value: <0.000195% CI: [-5.69, -2.16]Mixed Models Analysis
p-value: <0.000195% CI: [-6.46, -2.63]Mixed Models Analysis
Secondary
Change in Total Alcohol Consumption (TAC) From Baseline at Week 12
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in Total Alcohol Consumption (TAC) From Baseline at Week 12 | -44.90 g/day | Standard Error 2.01 |
| Nalmefene Hydrochloride 10 mg | Change in Total Alcohol Consumption (TAC) From Baseline at Week 12 | -45.36 g/day | Standard Error 2.32 |
| Placebo | Change in Total Alcohol Consumption (TAC) From Baseline at Week 12 | -32.43 g/day | Standard Error 1.91 |
Comparison: Change in total alcohol consumption (TAC) from baseline at Week 12p-value: <0.000195% CI: [-17.81, -7.13]Mixed Models Analysis
p-value: <0.000195% CI: [-18.72, -7.15]Mixed Models Analysis
Secondary
Change in Total Alcohol Consumption (TAC) From Baseline at Week 24
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nalmefene Hydrochloride 20 mg | Change in Total Alcohol Consumption (TAC) From Baseline at Week 24 | -49.43 g/day | Standard Error 2.13 |
| Nalmefene Hydrochloride 10 mg | Change in Total Alcohol Consumption (TAC) From Baseline at Week 24 | -49.55 g/day | Standard Error 2.45 |
| Placebo | Change in Total Alcohol Consumption (TAC) From Baseline at Week 24 | -38.28 g/day | Standard Error 1.99 |
p-value: 0.000195% CI: [-16.77, -5.53]Mixed Models Analysis
p-value: 0.000395% CI: [-17.37, -5.17]Mixed Models Analysis
Secondary
HDD Responder Rate at Week 12
Proportion of patients with ≤4 HDDs
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | HDD Responder Rate at Week 12 | 35.0 percentage |
| Nalmefene Hydrochloride 10 mg | HDD Responder Rate at Week 12 | 36.4 percentage |
| Placebo | HDD Responder Rate at Week 12 | 19.2 percentage |
p-value: 0.000295% CI: [7.1, 23.3]Cochran-Mantel-Haenszel
p-value: 0.000195% CI: [8.9, 26.9]Cochran-Mantel-Haenszel
Secondary
HDD Responder Rate at Week 24
Proportion of patients with ≤4 HDDs
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | HDD Responder Rate at Week 24 | 33.9 percentage |
| Nalmefene Hydrochloride 10 mg | HDD Responder Rate at Week 24 | 44.0 percentage |
| Placebo | HDD Responder Rate at Week 24 | 25.2 percentage |
p-value: 0.072495% CI: [-0.7, 16.7]Cochran-Mantel-Haenszel
p-value: 0.000195% CI: [9.9, 29.2]Cochran-Mantel-Haenszel
Secondary
Response Low Drinking Risk Level (RLDRL) at Week 12
Proportion of patients with low or lower drinking risk level
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | Response Low Drinking Risk Level (RLDRL) at Week 12 | 29.6 percentage |
| Nalmefene Hydrochloride 10 mg | Response Low Drinking Risk Level (RLDRL) at Week 12 | 25.3 percentage |
| Placebo | Response Low Drinking Risk Level (RLDRL) at Week 12 | 10.7 percentage |
p-value: <0.000195% CI: [10.5, 25.1]Cochran-Mantel-Haenszel
p-value: 0.000295% CI: [6.4, 22.2]Cochran-Mantel-Haenszel
Secondary
Response Low Drinking Risk Level (RLDRL) at Week 24
Proportion of patients with low or lower drinking risk level
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | Response Low Drinking Risk Level (RLDRL) at Week 24 | 29.6 percentage |
| Nalmefene Hydrochloride 10 mg | Response Low Drinking Risk Level (RLDRL) at Week 24 | 32.6 percentage |
| Placebo | Response Low Drinking Risk Level (RLDRL) at Week 24 | 17.6 percentage |
p-value: 0.007995% CI: [2.9, 19.1]Cochran-Mantel-Haenszel
p-value: 0.00195% CI: [5.8, 23.9]Cochran-Mantel-Haenszel
Secondary
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
Time frame: Week 12
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | Response Shift Drinking Risk Level (RSDRL) at Week 12 | 41.3 percentage |
| Nalmefene Hydrochloride 10 mg | Response Shift Drinking Risk Level (RSDRL) at Week 12 | 35.7 percentage |
| Placebo | Response Shift Drinking Risk Level (RSDRL) at Week 12 | 20.1 percentage |
p-value: <0.000195% CI: [13.6, 30.4]Cochran-Mantel-Haenszel
p-value: 0.000795% CI: [6.5, 25]Cochran-Mantel-Haenszel
Secondary
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
Time frame: Week 24
Population: Full analysis set, which included all patients who had data on the number of HDDs at baseline and at ≥1 time point after initiation of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nalmefene Hydrochloride 20 mg | Response Shift Drinking Risk Level (RSDRL) at Week 24 | 44.4 percentage |
| Nalmefene Hydrochloride 10 mg | Response Shift Drinking Risk Level (RSDRL) at Week 24 | 47.5 percentage |
| Placebo | Response Shift Drinking Risk Level (RSDRL) at Week 24 | 27.5 percentage |
p-value: 0.000295% CI: [8.8, 27.2]Cochran-Mantel-Haenszel
p-value: 0.000195% CI: [10.4, 30.8]Cochran-Mantel-Haenszel