The efficacy of VIVITROL in the treatment of opioid dependence was evaluated in a 24-week, placebo-controlled, multicenter, double-blind, randomized trial of opioid-dependent (DSM-IV) outpatients who were completing or had recently completed detoxification.
Endpoints2
The primary endpoint was confirmed opioid abstinence during Weeks 5-24.
- Confirmed abstinence was defined as a negative urine drug test (UDT) for opioids and no self-reported drug use
- Weeks 1-4 were omitted from the endpoint to allow for stabilization of abstinence
With VIVITROL and counseling, 36% of patients in the pivotal trial maintained complete abstinence for Weeks 5-24 vs 23% with placebo and counseling1,2
Subject sustaining varying percentages of opioid-free weeks*
- Data were not collected during Weeks 1-4 of the trial to allow for stabilization of abstinence.
- The median of the VIVITROL group had confirmed abstinence* for 90% of the weeks in the evaluation period vs 35% for the median of the placebo group.
Secondary endpoints
Secondary endpoints were self-reported opioid-free days, opioid craving scores, treatment retention data, and relapses to physiological opioid dependence.
Secondary endpoint: Mean change in opioid craving
Mean change in self-reported opioid craving‡ in patients receiving VIVITROL and counseling vs placebo2,3
Patients given VIVITROL had a -10.1 mean change in craving visual analog scale (VAS) score, while patients given placebo had a +0.7 change in craving VAS score.
Mean change in self-reported craving score
Patients in the VIVITROL group had a 55% lower mean craving score at 24 weeks than the mean score at baseline. Patients in the placebo group had a 3% higher mean craving score at 24 weeks than the mean score at baseline.3
‡Craving (described as a “need for opioids”) was self-reported weekly according to a VAS of 0 to 100, with 0 being “not at all” and 100 being “very much so.” ¶Psychosocial support consisted of biweekly sessions of individual drug counseling, adapted for opioid dependence.Secondary endpoint: Number of days of retention
Secondary endpoint: Number of patients with a positive naloxone challenge at the end of 24 weeks: 1 VIVITROL patient vs 17 placebo patients.
Other Outcomes
A greater percentage of subjects in the VIVITROL group (53%, n=67) remained in the study compared to the placebo group (38%, n=47; =0.0171).
Please see study limitations.Study design2
Prior to treatment initiation, patients were voluntarily seeking treatment, completing ≤30 days of inpatient opioid detoxification and not taking opioids for at least 7 days.
Participants were randomized to receive VIVITROL (n=126) or placebo (n=124), with a UDT every week, psychosocial support every 2 weeks, and treatment injection every 4 weeks.
After randomization, there was a 4-week period for treatment engagement during which opioid use, if it occurred, was allowed. This period was not included in the analysis. Subjects provided additional self-report of opioid use.
| VIVITROL (n=126) | Placebo (n=124) | |
|---|---|---|
| Age in years | 29.4 (±4.8) | 29.7 (±3.6) |
| Men | 113 (90%) | 107 (86%) |
| White | 124 (98%) | 124 (100%) |
| Duration of opioid dependence in years | 9.1 (±4.5) | 10.0 (±3.9) |
| Days of prestudy inpatient detoxification | 18 (±9) | 18 (±7) |
| Opioid craving scale | 18 (±23) | 22 (±24) |
| HIV serology positive | 51 (40%) | 52 (42%) |
| Hepatitis C positive | 111 (88%) | 117 (94%) |
Data are mean (SD) or number (%).
- Retention in the placebo group might have been reduced by recognition, upon opioid use, that one was on placebo
- Or, among patients in the placebo group who had relapsed to regular opioid use, by reluctance to return to the clinic and face a withdrawal reaction from a naloxone challenge test
- The placebo group showed a substantial retention and response profile, and a markedly higher rate of positive naloxone challenge tests
- The high retention rate might have been influenced by:
- Inclusion criterion that patients have someone available to supervise attendance
- Provision of individual counselling
- Absence of alternative treatments in Russia
- Promise of active VIVITROL treatment for all patients after 6 months, in the subsequent open-label extension safety study
- Analyses of group central tendencies (median, mean) may not reflect the experience of individual patients
Adverse reactions in opioid dependence pivotal trial
Treatment-emergent adverse reactions (occurring in ≥2% of patients and more frequently in the VIVITROL group than the placebo group) in the pivotal trial for opioid dependence1
| Events | VIVITROL 380 mg with psychosocial support (n=126) | Placebo with psychosocial support (n=124) |
|---|---|---|
| Alanine aminotransferase increased | 13% | 6% |
| Aspartate aminotransferase increased | 10% | 2% |
| Gamma-glutamyltransferase increased | 7% | 3% |
| Nasopharyngitis | 7% | 2% |
| Insomnia | 6% | 1% |
| Influenza | 5% | 4% |
| Hypertension | 5% | 3% |
| Injection site pain | 5% | 1% |
| Toothache | 4% | 2% |
| Headache | 3% | 2% |
Please see the complete list of adverse reactions in the VIVITROL
Prescribing Information.
Discontinuation rates due to adverse events1
Opioid dependence pivotal trial
¶Psychosocial support consisted of biweekly session of individual drug counseling, adapted for opioid dependence.See Important Safety Information.
See Prescribing Information. Review Medication Guide with your patients.