Clinical data on the safety and efficacy of SUBOXONE and SUBUTEX are derived from studies of buprenorphine sublingual tablet formulations, with and without naloxone, and from studies of sublingual administration of a more bioavailable ethanolic solution of buprenorphine.

SUBOXONE tablets have been studied in 575 patients, SUBUTEX tablets in 1834 patients and buprenorphine sublingual solutions in 2470 patients. A total of 1270 females have received buprenorphine in clinical trials. Dosing recommendations are based on data from one trial of both tablet formulations and two trials of the ethanolic solution. All trials used buprenorphine in conjunction with psychosocial counseling as part of a comprehensive addiction treatment program. There have been no clinical studies conducted to assess the efficacy of buprenorphine as the only component of treatment.

In a double blind placebo- and active controlled study, 326 heroin-addicted subjects were randomly assigned to either SUBOXONE 16 mg per day, 16 mg SUBUTEX per day or placebo tablets. For subjects randomized to either active treatment, dosing began with one 8 mg tablet of SUBUTEX on Day 1, followed by 16 mg (two 8 mg tablets) of SUBUTEX on Day 2. On Day 3, those randomized to receive SUBOXONE were switched to the combination tablet. Subjects randomized to placebo received one placebo tablet on Day 1 and two placebo tablets per day thereafter for four weeks. Subjects were seen daily in the clinic (Monday through Friday) for dosing and efficacy assessments. Take-home doses were provided for weekends. Subjects were instructed to hold the medication under the tongue for approximately 5 to 10 minutes until completely dissolved. Subjects received one hour of individual counseling per week and a single session of HIV education. The primary study comparison was to assess the efficacy of SUBUTEX and SUBOXONE individually against placebo. The percentage of thrice-weekly urine samples that were negative for non-study opioids was statistically higher for both SUBUTEX and SUBOXONE, than for placebo.

In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution to a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual solution of buprenorphine at 8 mg/day (a dose which is roughly comparable to a dose of 12 mg/day of SUBUTEX or SUBOXONE), or two relatively low doses of active control, one of which was low enough to serve as an alternative to placebo, during a 3-10 day induction phase, a 16-week maintenance phase and a 7-week detoxification phase. Buprenorphine was titrated to maintenance dose by Day 3; active control doses were titrated more gradually.

Maintenance dosing continued through Week 17, and then medications were tapered by approximately 20-30% per week over Weeks 18-24, with placebo dosing for the last two weeks. Subjects received individual and/or group counseling weekly.

Based on retention in treatment and the percentage of thrice-weekly urine samples negative for non-study opioids, buprenorphine was more effective than the low dose of the control, in keeping heroin addicts in treatment and in reducing their use of opioids while in treatment. The effectiveness of buprenorphine, 8 mg per day was similar to that of the moderate active control dose, but equivalence was not demonstrated.

In a dose-controlled, double-blind, parallel-group, 16-week study, 731 subjects were randomized to receive one of four doses of buprenorphine ethanolic solution. Buprenorphine was titrated to maintenance doses over 1-4 days (Table 2) and continued for 16 weeks. Subjects received at least one session of AIDS education and additional counseling ranging from one hour per month to one hour per week, depending on site.

* Sublingual solution. Doses in this tabe cannot necessarily be delivered in tablet form, but for comparison purposes:

2 mg solution would be roughly equivalent to 3 mg tablet

4 mg solution would be roughly equivalent to 6 mg tablet

8 mg solution would be roughly equivalent to 12 mg tablet

16 mg solution would be roughly equivalent to 24 mg tablet  


  


Based on retention in treatment and the percentage of thrice-weekly urine samples negative for non-study opioids, the three highest tested doses were superior to the 1 mg dose. Therefore, this study showed that a range of buprenorphine doses may be effective. The 1 mg dose of buprenorphine sublingual solution can be considered to be somewhat lower than a 2 mg tablet dose. The other doses used in the study encompass a range of tablet doses from approximately 6 mg to approximately 24 mg.