Novel Buccal Film Formulation of Buprenorphine-Naloxone for the Maintenance Treatment of Opioid Dependence: A 12-Week Conversion Study.

PURPOSE

The purpose of this study was to provide a preliminary assessment of the safety, tolerability, symptom control, and acceptability of buprenorphine-naloxone buccal film (BBN) for the maintenance treatment of opioid dependence in patients converted from buprenorphine-naloxone sublingual tablet or film (SLBN), as well as to determine the conversion ratio for switching patients from SLBN to BBN.

METHODS

This open-label study included adult opioid-dependent subjects stabilized on 8/2 to 32/8 mg/d of SLBN for a minimum of 30 days. Study subjects were converted to a bioequivalent dose of BBN and maintained for 12 weeks.

FINDINGS

A total of 249 subjects (mean age 38.7 years, 65.9% male) were converted from SLBN to a single daily dose of BBN, and 79.1% completed the 12-week study. Adverse events and withdrawal symptoms led to discontinuation in 2.4% and 2.0% of BBN-treated subjects, respectively. Rates of constipation reported at baseline declined from 41% just before the initial BBN dose and within 24 hours of the last SLBN dose to 13% after 12 weeks of BBN treatment; treatment-emergent constipation was reported by 2.8% of BBN-treated subjects. Oral mucosal abnormalities were identified in 5% and 0.6% of systematic oral examinations in SLBN- and BBN-treated subjects, respectively. A total of 34 subjects had Clinical Opiate Withdrawal Scale total scores ranging from 10 to 25 (overall mean, 13.8) within 24 hours of taking their last SLBN dose, and scores for these subjects were reduced to a range of 0 to 3 (overall mean, 0.7) at 3 hours after the initial dose of BBN. Treatment compliance was high (108%); <1% of urine samples were buprenorphine-free, and 92.4% of BBN-treated subjects did not have a urine sample that tested positive for a non-prescribed opioid. A total of 91.3% subjects rated the taste of BBN as pleasant or neutral, and 82.5% rated BBN ease of use as easy or neutral. The overall mean final dose of BBN was 8.0/1.4 mg/d, yielding a 2:1 buprenorphine conversion ratio.

IMPLICATIONS

Although these results should be considered preliminary due to the open-label design, BBN was overall safe and well tolerated, and seemed to provide adequate symptom control, in the treatment of opioid-dependent subjects previously controlled on SLBN for a minimum of 30 days. There was good adherence to study medication and favorable patient acceptance of the buccal formulation. The SLBN/BBN buprenorphine conversion ratio was 2:1. ClinicalTrials.gov identifier: NCT01666119.