Clinical Evaluation of Abuse Potential of Buprenorphine /Samidorphan (BUP/SAM) Combination

Introduction: Buprenorphine (BUP)/samidorphan (SAM) combination is an opioid system modulator being investigated as adjunctive treatment for major depressive disorder (MDD). The human abuse potential (HAP) of BUP/SAM was assessed in Study 212 and through an evaluation of the clinical experience of patients with MDD across 4 clinical studies.

Methods: In Study 212, nondependent, recreational, opioid users were randomized to 6 treatments in a blinded, crossover design: placebo (PBO), BUP/SAM at target therapeutic (2 mg/2 mg) and supratherapeutic doses (8 mg/8 mg, 16 mg/16 mg), and BUP (8 mg, 16 mg). The primary endpoint was maximum effect (Emax) for “At the Moment” Drug Liking Visual Analog Scale (DL-VAS). Pooled safety data from the MDD clinical studies were interrogated for adverse events (AEs) associated with abuse, dependence, or withdrawal, and signs of withdrawal with the Clinical Opioid Withdrawal Scale (COWS).

Results: In Study 212 (n=38), Emax DL-VAS scores for BUP/SAM 2 mg/2 mg and PBO were similar (median within-subject difference [90% CI]: 2.5 [0.0–9.0]). Scores for all BUP/SAM dose groups were significantly lower than for either BUP dose. Supratherapeutic BUP/SAM doses had higher Emax DL-VAS scores than PBO, but the differences were small. Across the MDD clinical studies (n=961), the incidence of euphoria-related AEs was 1.6% with BUP/SAM 2 mg/2 mg and 0.2% with PBO. Euphoria events typically resolved with continued treatment. No patients receiving BUP/SAM reported abuse behavior AEs. AEs and COWS assessments showed no evidence of dependence or withdrawal.

Conclusions: These findings indicate a low abuse potential for BUP/SAM.