Safety of a Rapidly Dissolving Buprenorphine/Naloxone Sublingual Tablet (BNX-RDT) for Treatment of Opioid Dependence: A Multicenter, Open-label Extension Study

Abstract

Objective: To assess the safety of rapidly dissolving buprenorphine/naloxone sublingual tablets (BNX-RDT) in opioid-dependent patients.

Methods: This open-label, 24-week extension study enrolled patients who completed primary trials of BNX-RDT. Daily tablet doses ranged from 5.7 to 17.1 mg. The primary endpoint was safety; secondary assessments included opioid cravings, addiction severity, health-related quality of life (QOL), and workplace productivity at screening (final day of the primary trials) through study end, with changes measured from baseline of the primary trials.

Results: In all, 665 patients received treatment; 292 (43.9%) completed the study. A total of 258 patients (38.8%) reported 557 treatment-emergent adverse events, most commonly headache (3.2%) and constipation (3.0%). Craving scores showed continued improvement on 100-mm visual analog scale (mean change from primary trial baseline, -52.8 at screening; mean change from extension trial baseline, -60.5 at week 24). Reductions in addiction severity from baseline of both the primary and extension trial were maintained through week 24 on multiple assessments, as were improvements in QOL on Short Form 36. Employment increased by 15% and mean (SD) hours worked per week increased by 4.6 (20.1) from baseline to study end. Mean (SD) scores for impact of opioid dependence on work productivity improved from 4.7 (3.0) at baseline to 0.9 (1.8) at study end (11-point scale).

Conclusions: Extended treatment with BNX-RDT demonstrated a safety profile similar to other BNX formulations, reduced opioid cravings, and improved both QOL and work productivity. Continued treatment may enable patients to advance in recovery and return to normal functioning.

FIGURE 1

Mean (SD) VAS craving scores versus primary study baseline mean score of 70.8, safety population. Patients treated with BNX-RDT rated scores for cravings on a 100-mm VAS for which 0 mm = “no cravings” and 100 mm = “the most intensive craving I have ever had.”

FIGURE 2

Mean (SD) SF-36 item and component summary scores at screening and week 24, safety population. Normalized scores for the 8 subdomains and MCS and PCS T-scores are measured on a scale of 0 to 100, with higher scores being more favorable. Mean general population (2005–2006) SF-36 item scores ranged from 49.47 (Role–Physical) to 54.27 (Mental Health); component summary scores were 49.22 for the PCS and 53.78 for the MCS (Maglinte et al., 2012). ^aOne patient did not have data available for the assessment of General Health at day 1 or week 24.