The Bioavailability of CHF6563, an Ethanol-Free, Sublingual Neonatal Buprenorphine Formulation: A Bridging Study Conducted in Adults

Abstract

OBJECTIVE Sublingual buprenorphine has demonstrated efficacy for treatment of the neonatal opioid withdrawal syndrome (NOWS), but the current formulation used in clinical practice contains 30% ethanol. Ethanol as a pharmacologically active excipient ideally should be removed from neonatal formulations. The objective of this study was to determine the relative bioavailability of a novel ethanol-free ­formulation (CHF6563) compared with the commonly used ethanolic solution in a phase I, open-label, 2-period, ­single-dose, crossover study in healthy adults. METHODS Eighteen adult opioid-naïve volunteers were administered one of the formulations in a randomized crossover treatment. After a 10-day washout period, subjects received the other formulation. Serial blood samples were drawn for pharmacokinetic analysis over 48 hours. RESULTS The geometric mean ratio (90% CIs) of the ethanol-free buprenorphine solution AUC0–last was 0.80 (0.65–0.99) and Cmax was 0.81 (0.66–0.99) compared with reference ethanolic formulation. The ­ethanol-free formulation had a greater degree of intersubject variability than the ethanol-containing ­reference formulation (coefficient of variation of 59% vs 31.5%, respectively, for AUC0–last). CONCLUSIONS In an adult population, a novel ethanol-free formulation of buprenorphine containing widely used excipients demonstrated a slight decrease in bioavailability when compared with an ethanolic solution. These results will inform those seeking to develop ethanol-free pediatric drug formulations.