A 24-week, multicenter, double-blind, randomized, placebo-controlled trial of opioid-dependent (DSM-IV) outpatients, ≥18 years of age1,2
PIVOTAL STUDY DATA1,2
- 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)
- Every week—urine drug test
- Every 2 weeks—psychosocial support, consisting of sessions of individual drug counseling, adapted for opioid dependence
- Every 4 weeks—treatment injection
OPIOID STUDY DESIGN1
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.
- Past/present history of an AIDS-indicator disease
- Evidence of hepatic failure
- Active hepatitis and/or aspartate aminotransferase or alanine aminotransferase >3 times the upper limit of normal
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
THE EFFICACY OF VIVITROL1
Response profile of patients who achieved complete abstinence during Weeks 5–24
- Complete abstinence or opioid-free was defined as a negative urine drug test for opioids and no self-reported opioid use
- Weeks 1-4 were omitted from this endpoint to allow for stabilization of abstinence
- Self-reported opioid-free days
- Craving scores
- Treatment retention days
- Relapse to physiological opioid dependence
DEMOGRAPHICS AND CLINICAL BASELINE CHARACTERISTICS
|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%)|
Data are mean (standard deviation [SD]) or number (%)
COMPLETE OPIOID ABSTINENCE1,2*
With VIVITROL and counseling, more patients achieved complete abstinence vs placebo.
- Complete abstinence was sustained by 36% of VIVITROL patients (n=45) compared with 23% of patients treated with placebo (n=28), during Weeks 5-24 (P=0.0224)
SUBJECTS SUSTAINING VARYING PERCENTAGES OF OPIOID-FREE WEEKS
- 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
*Complete or confirmed abstinence was defined as a negative urine drug test 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 were not collected during Weeks 1-4 of the trial to allow for stabilization of abstinence.
SELF-REPORTED OPIOID-FREE‡ DAYS
Percentage of opioid-free days with VIVITROL and counseling vs placebo.1
- The median number of opioid-free days at baseline was zero for both the VIVITROL and placebo groups3
MEDIAN OPIOID-FREE DAYS WITH VIVITROL AND COUNSELING VS PLACEBO1
‡Opioid-free was defined as no self-reported opioid use. §Psychosocial support consisted of bi-weekly counseling sessions of individual drug counseling, adapted for opioid dependence.
SECONDARY ENDPOINT: CRAVING
Mean change in opioid craving in patients receiving VIVITROL and counseling vs placebo.1
- Mean change in self-reported craving in patients receiving VIVITROL vs placebo over 24 weeks1
- Patients treated with VIVITROL had an average 10.1 decrease in baseline craving as measured by the VAS score, while patients who received placebo had a 0.7 increase in baseline craving as measured by VAS score (P<0.0001, adjusted)1
Change in Mean Craving Score3
- VIVITROL: 55% lower mean craving score at 24 weeks compared to baseline
- Placebo: 3% higher mean craving score at 24 weeks compared to baseline
IIPsychosocial support consisted of bi-weekly counseling sessions of individual drug counseling, adapted for opioid dependence.
The number of days the median patient stayed in treatment in patients receiving Vivitrol vs PLACEBO with counseling
- A greater percentage of subjects in the VIVITROL group (n=67, 53%) remained in the study compared to the placebo group (n=47, 38%); P=0.0171
At the end of the study period (168 days), the median of the VIVITROL group had not dropped out1
- The median time in treatment was >168 days for VIVITROL patients vs 96 days with placebo
- Analyses of group central tendencies (median, mean) do not reflect the experience of individual patients
MEDIAN TREATMENT TIME
¶Psychosocial support consisted of bi-weekly counseling sessions of individual drug counseling, adapted for opioid dependence.
SECONDARY ENDPOINT: RELAPSE TO PHYSIOLOGICAL OPIOID DEPENDENCE
One patient on VIVITROL (<1%) discontinued due to positive naloxone challenge, indicating physical dependence had been re-established, compared to 17 patients on placebo (14%)1,2
94% fewer naloxone-confirmed
relapses to dependence.1
ADVERSE REACTIONS IN OPIOID-DEPENDENCE PIVOTAL TRIAL2
Adverse reactions that occurred in ≥2% of patients with opioid dependence treated with VIVITROL and occurred more frequently in the VIVITROL group vs the placebo group.
|VIVITROL 380 mg with
|Alanine aminotransferase increased||13%||6%|
|Aspartate aminotransferase increased||10%||2%|
|Injection site pain||5%||1%|
Please see complete list of adverse events in the VIVITROL Prescribing Information.
Discontinuation rates due to adverse events were similar in opioid-dependent patients treated with VIVITROL vs patients treated with placebo.DOWNLOAD THE VIVITROL BROCHURE TO DISCUSS WITH YOUR PATIENTS
The X:BOT study, “Comparative Effectiveness of Extended-Release Naltrexone Versus Buprenorphine-Nalaxone for Opioid Relapse Prevention,” provides additional useful information. Read about it now
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.
See Important Safety Information below. Discuss all benefits and risks with your patients. See Prescribing Information and Medication Guide with your patients.