Alcohol Dependence
Conditions
Keywords
Addiction, Alcoholism, Inpatient detoxification
Brief summary
VIVITROL is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with VIVITROL. This Phase 3B trial was designed to evaluate the efficacy and safety of VIVITROL versus placebo. Injections were administered to patients in whom abstinence was enforced by a period of inpatient hospitalization of 7 to 21 days.
Detailed description
The study consisted of 2 parts, Part A and Part B. Part A was a double-blind, placebo-controlled assessment of safety and efficacy of VIVITROL versus placebo for 3 months. Part B was an open-label extension to assess longer-term safety, durability of effect, and health economics of VIVITROL when administered for up to 9 additional months.
Interventions
DRUGVIVITROL 380 mg
Administered via IM injection once every 4 weeks.
DRUGPlacebo for VIVITROL 380 mg
Administered via IM injection once every 4 weeks.
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Primary Inclusion Criteria: * Current diagnosis of alcohol dependence, meeting at least 5 of DSM-IV criteria * Expected to complete inpatient treatment for alcohol dependence within 24 hours of randomization * Must have 7-21 days, inclusive, of inpatient treatment for alcohol dependence prior to first dose * Negative urine toxicological screen for opioids on the day of randomization * Women of childbearing potential must agree to use an approved method of contraception for the study duration Primary
Exclusion criteria
* Pregnancy or lactation * Evidence of hepatic failure including: ascites, bilirubin \>10% above upper limit of normal and/or esophageal variceal disease * Current dependence (within the past year) to benzodiazepines, opioids or cocaine by DSM-IV criteria * Use of any opioids and/or methadone within 14 days prior to the screening visit, or subjects likely to require opioid therapy during the study period * Use of oral naltrexone, acamprosate, or disulfiram within 14 days prior to screening * Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or PLG * Parole, probation, or pending legal proceedings having the potential for incarceration during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Participants by Heavy Drinking Rate | up to 12 weeks | Cumulative percentage (%) of subjects reporting heavy drinking by category reflecting the various cut-offs for percentage of days that were heavy drinking days. A heavy drinking day was defined as 4 or more alcohol drinks in 1 day for women, and 5 or more alcohol drinks in 1 day for men. The Timeline Follow-Back (TLFB) method (Sobell & Sobell: Humana Press, 1992) was utilized to collect subjects' daily drinking information (ie, the number of drinks consumed per day per subject which was retrospectively recalled and recorded in a diary). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longer-term Safety of VIVITROL | up to 1 year | Number of subjects reporting at least 1 treatment-emergent adverse event (TEAE) while on study. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VIVITROL 380 mg Arm includes all subjects who received at least 1 injection of VIVITROL. After successfully completing screening subjects were administered VIVITROL 380 mg by intramuscular (IM) injection every 4 weeks for a total of 3 injections. Randomization was 1:1 (VIVITROL:placebo) and stratified by site. | 152 |
| Placebo for VIVITROL 380 mg All subjects who received at least 1 injection of Placebo for VIVITROL. Arm includes all subjects who received at least 1 injection of placebo. After successfully completing screening subjects were administered placebo by intramuscular (IM) injection every 4 weeks for a total of 3 injections. Randomization was 1:1 (VIVITROL:placebo) and stratified by site. | 148 |
| Total | 300 |
Baseline characteristics
| Characteristic | VIVITROL 380 mg | Placebo for VIVITROL 380 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 152 Participants | 148 Participants | 300 Participants |
| Age Continuous | 45.5 years STANDARD_DEVIATION 8.5 | 46.1 years STANDARD_DEVIATION 8.3 | 45.8 years STANDARD_DEVIATION 8.4 |
| Region of Enrollment Austria | 10 participants | 10 participants | 20 participants |
| Region of Enrollment Germany | 142 participants | 138 participants | 280 participants |
| Sex: Female, Male Female | 33 Participants | 27 Participants | 60 Participants |
| Sex: Female, Male Male | 119 Participants | 121 Participants | 240 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 135 / 152 | 133 / 148 |
| serious Total, serious adverse events | 29 / 152 | 27 / 148 |
Outcome results
Primary
Cumulative Percentage of Participants by Heavy Drinking Rate
Cumulative percentage (%) of subjects reporting heavy drinking by category reflecting the various cut-offs for percentage of days that were heavy drinking days. A heavy drinking day was defined as 4 or more alcohol drinks in 1 day for women, and 5 or more alcohol drinks in 1 day for men. The Timeline Follow-Back (TLFB) method (Sobell & Sobell: Humana Press, 1992) was utilized to collect subjects' daily drinking information (ie, the number of drinks consumed per day per subject which was retrospectively recalled and recorded in a diary).
Time frame: up to 12 weeks
Population: The primary endpoint is based on percentage rate of heavy drinking days during the double-blind treatment period as per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 30% Heavy Drinking Days | 74.3 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 60% Heavy Drinking Days | 84.9 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 20% Heavy Drinking Days | 65.8 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 70% Heavy Drinking Days | 90.1 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 40% Heavy Drinking Days | 80.9 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 80% Heavy Drinking Days | 93.4 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 10% Heavy Drinking Days | 59.2 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 90% Heavy Drinking Days | 97.4 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 50% Heavy Drinking Days | 83.6 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 100% Heavy Drinking Days | 100.0 percentage of participants |
| Vivitrol | Cumulative Percentage of Participants by Heavy Drinking Rate | 0% Heavy Drinking Days | 40.8 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 100% Heavy Drinking Days | 100.0 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | 0% Heavy Drinking Days | 47.3 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 10% Heavy Drinking Days | 59.5 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 20% Heavy Drinking Days | 72.3 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 30% Heavy Drinking Days | 79.1 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 40% Heavy Drinking Days | 83.1 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 50% Heavy Drinking Days | 85.1 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 60% Heavy Drinking Days | 87.2 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 70% Heavy Drinking Days | 89.9 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 80% Heavy Drinking Days | 94.6 percentage of participants |
| Placebo | Cumulative Percentage of Participants by Heavy Drinking Rate | <= 90% Heavy Drinking Days | 98.6 percentage of participants |
Comparison: The null hypothesis that there is no difference between two treatment groups (i.e. Placebo and Vivitrol) was tested using a two-sided Van der Waerden test. Response profiles were tabulated as a cumulative percent of subjects at each decile of percent heavy drinking days.p-value: 0.336Van der Waerden test
Secondary
Longer-term Safety of VIVITROL
Number of subjects reporting at least 1 treatment-emergent adverse event (TEAE) while on study.
Time frame: up to 1 year