Alcoholism
Conditions
Keywords
Alcoholism, Alcohol dependence
Brief summary
This was a Phase 3 multicenter randomized, open-label, safety study assessing the safety of repeat doses of Medisorb® naltrexone 380 mg (VIVITROL®) administered for up to 1 year to adults with alcohol and/or opioid dependence as defined by Diagnostic and Statistical Manual of Mental Health Disorders (DSM-IV) criteria. Eligible subjects were randomized in a 6:1 ratio to receive 1 of the following regimens: a single intramuscular (IM) injection of VIVITROL administered once every 4 weeks or oral naltrexone 50 mg administered daily.
Detailed description
Safety evaluations included physical examinations, electrocardiograms (ECGs), laboratory measures (including plasma concentrations of naltrexone and 6β-naltrexol), assessments of injection sites, and adverse events (AEs). All subjects received psychosocial support at each study visit for the duration of the study, with interim telephone contact 2 weeks after each monthly visit.
Interventions
Administered via intramuscular (IM) injection once every 4 weeks for up to 1 year.
DRUGOral naltrexone 50 mg
Tablet taken orally once daily for up to 1 year
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Primary Inclusion Criteria: * Current diagnosis of DSM-IV alcohol dependence and/or diagnosis of DSM-IV opiate dependence within 3 months prior to screening * 18 years or older * Desire to seek treatment for alcohol and/or opiate abuse/dependence * Agree to use contraception for the study duration if of childbearing potential * Written informed consent and willingness to perform study procedures * Stable address and phone and at least 1 source of contact information (eg, family member, significant other) Primary
Exclusion criteria
* Presence of opiates in the urine (as determined by urine drug test) on Day 0 prior to naltrexone treatment * Clinically significant medical/psychological condition or abnormality at screening (ie, physical examination, electrocardiogram \[ECG\], hematology or blood chemistry evaluation, or urinalysis findings) * Clinically significant active hepatitis or hepatic failure evidenced by 1 of the following: aspartate transaminase (AST) or alanine transaminase (ALT) higher than 3 times the upper limit of normal (3xULN), hyperbilirubinemia (bilirubin \>10% above ULN), creatine phosphokinase (CPK) higher than 10xULN, prolonged prothrombin time(international normalized ratio ≥1.7), ascites, or esophageal variceal disease * Manifestation of suicidal ideation, psychotic symptoms (including significant violent behavior), or psychiatric disorders that would compromise ability to complete the study * Participation in a formal methadone program currently or within prior 3 years * More than 2 prior medically supervised detoxification treatments in prior 3 years * Pregnancy or lactation * Current prescribed opiate therapy, or receipt of opiates within 7 days prior to study drug dosing, or ongoing medical condition likely to require prescribed opiate therapy during study period * Failed naloxone challenge on Day 0 (the challenge could be repeated up to 2 times, with at least 24 hours between attempts) * Participation in a clinical trial within 30 days of screening * Previous enrollment in a VIVITROL clinical trial * Receipt of any drug product administered as a gluteal injection within 180 days prior to Day 0 or anticipated need for gluteal injections during study period * Intolerance and/or hypersensitivity to naltrexone, naloxone, or polylactide-co-polymers such as polylactide-co-glycolide (PLG)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting at Least 1 Treatment-emergent Adverse Event (TEAE) While on Study | up to 1 year | A TEAE was defined as any adverse event (AE) that started or worsened on or after the administration of the first dose of study medication through 30 days after the end of study treatment. |
Participant flow
Pre-assignment details
Enrollment was monitored to ensure adequate representation of alcohol-dependent and opioid-dependent patients as defined by Diagnostic and Statistical Manual of Mental Health Disorders (DSM-IV) criteria, and was stratified by alcohol dependence alone versus opioid or mixed substance abuse (ie, alcohol and opioid dependence).
Participants by arm
| Arm | Count |
|---|---|
| Medisorb Naltrexone 380 mg (VIVITROL) Administered once every 4 weeks via intramuscular (IM) injection for up to 1 year. | 371 |
| Oral Naltrexone 50 mg Oral tablet taken once each day for up to 1 year. | 65 |
| Total | 436 |
Baseline characteristics
| Characteristic | Oral Naltrexone 50 mg | Medisorb Naltrexone 380 mg (VIVITROL) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 3 Participants | 3 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 64 Participants | 364 Participants | 428 Participants |
| Age Continuous | 40.5 years STANDARD_DEVIATION 11.4 | 40.7 years STANDARD_DEVIATION 11.2 | 40.7 years STANDARD_DEVIATION 11.3 |
| Region of Enrollment United States | 65 participants | 371 participants | 436 participants |
| Sex: Female, Male Female | 23 Participants | 138 Participants | 161 Participants |
| Sex: Female, Male Male | 42 Participants | 233 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 336 / 371 | 53 / 65 |
| serious Total, serious adverse events | 49 / 371 | 5 / 65 |
Outcome results
Primary
Number of Subjects Reporting at Least 1 Treatment-emergent Adverse Event (TEAE) While on Study
A TEAE was defined as any adverse event (AE) that started or worsened on or after the administration of the first dose of study medication through 30 days after the end of study treatment.
Time frame: up to 1 year
Population: All subjects who received at least 1 dose of study drug are included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medisorb Naltrexone 380 mg (VIVITROL) | Number of Subjects Reporting at Least 1 Treatment-emergent Adverse Event (TEAE) While on Study | 336 Participants |
| Oral Naltrexone 50 mg | Number of Subjects Reporting at Least 1 Treatment-emergent Adverse Event (TEAE) While on Study | 53 Participants |