OPIOID DEPENDENCE PIVOTAL STUDY
VIVITROL and counseling may help prevent relapse to opioid dependence in your appropriate opioid-detoxed patients1
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 detoxification2
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 urine drug test (UDT) every week, psychosocial support every 2 weeks, and treatment injection every 4 weeks.
The age range for study participants was between 21 and 52 years, with an average age of 29.4 years. The duration of opioid dependence ranged from 1 to 26 years, with more patients in the VIVITROL group reporting shorter duration. For example, duration of use of <10 years was 47% vs 36% for the VIVITROL group vs the placebo group, respectively.
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.
ENDPOINTS2
The primary endpoint was the confirmed opioid abstinence in the VIVITROL group in comparison to the placebo group.
- Confirmed abstinence was defined as a negative UDT for opioids and no self-reported drug use
- Weeks 1-4 were omitted from the endpoint to allow for stabilization of abstinence
Secondary endpoints were self-reported opioid-free days, opioid craving scores, treatment retention days, and relapses to physiological opioid dependence.
Please see below for full study limitations.
Study participants
Demographics and clinical baseline characteristic2
| 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 pre-study 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%) |
Study Limitations2
-
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 counseling
- 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) do not reflect the experience of individual patients
VIVITROL and counseling may help your opioid-dependent patients achieve more opioid-free weeks following opioid detox1,2
With VIVITROL and counseling, 36% of patients in the pivotal trial maintained complete abstinence for Weeks 5-24 vs 23% with placebo and counseling
The primary endpoint was the confirmed abstinence in the VIVITROL group in comparison to the placebo group. Secondary endpoints include self-reported opioid-free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence.
Subjects 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.
Number of patients with a positive naloxone challenge (1 VIVITROL patient vs 17 placebo patients) at the end of 24 weeks.
*Confirmed abstinence or “opioid-free” was defined as a negative UDT for opioids and no self-reported opioid use. †Psychosocial support consisted of bi-weekly counseling sessions of individual drug counseling, adapted for opioid dependence.Data represented as the median.
Secondary Endpoint:
Mean change in opioid craving2
Mean change in self-reported opioid craving‡ in patients receiving VIVITROL and counseling vs placebo
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 score2,3
- 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
Secondary Endpoint:
Median time in treatment2
A greater percentage of subjects in the VIVITROL group (53%, n=67) remained in the study compared to the placebo group (38%, n=47; P=0.0171)
- At the end of the study period (168 days), the median VIVITROL patient had not dropped out
Adverse reactions in opioid dependence pivotal trial1
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 dependence
| 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
VIVITROL is not right for everyone. There are significant risks from VIVITROL treatment, including risk of opioid overdose, injection site reactions, and sudden opioid withdrawal. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose. See Important Safety Information below. See Prescribing Information. Review Medication Guide with your patients.
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REPRESENTATIVE
Request a visit from a VIVITROL representative to learn more about how VIVITROL may help your appropriate patients with opioid dependence or alcohol dependence.
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LEARN ABOUT THE VIVITROL®
CO-PAY SAVINGS PROGRAM
Learn how the VIVITROL® Co-pay Savings Program may assist eligible¶ patients with out-of-pocket expenses for their VIVITROL prescriptions.
LEARN MOREReferences: 1. VIVITROL [prescribing information]. Waltham, MA: Alkermes, Inc; rev March 2021. 2. Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomized trial. Lancet. 2011;377(9776):1506-1513. 3. Data on file. Alkermes, Inc. Waltham, MA.
¶Terms and Conditions
Eligibility for Alkermes-Sponsored Co-pay Savings. This offer is only available to patients 18 years or older, with a prescription consistent with the Prescribing Information and the patient is not enrolled in, or covered by, any local, state, federal or other government program that pays for any portion of medication costs, including but not limited to Medicare, including Medicare Part D or Medicare Advantage plans; Medicaid, including Medicaid Managed Care and Alternative Benefit Plans under the Affordable Care Act; Medigap; VA; DOD; TRICARE; or a residential correctional program.
Additional Terms of Use: This offer is not conditioned on any past, present, or future purchase, including refills. Alkermes reserves the right to rescind, revoke, or amend this offer, program eligibility, and requirements at any time without notice. This offer is limited to one per patient, may not be used with any other offer, is not transferable and may not be sold, purchased or traded, or offered for sale, purchase or trade. Void where prohibited by law. Program Administrator or its designee will have the right upon reasonable prior written notice, during normal business hours, and subject to applicable law, to audit compliance with this program.