Buprenorphine Buccal Film Versus Oxycodone: Pupillometry and Respiratory Depression Effects in a Phase 1 Trial

INTRODUCTION: A recent phase 1 placebo-controlled study demonstrated that oxycodone administration results in a significant dose-dependent reduction in respiratory drive in response to hypercapnia, whereas buprenorphine buccal film does not (ClinicalTrials.gov, NCT03996694). In addition to respiratory drive, pupillometry was also assessed. Here we investigate the correlation between respiratory drive and pupil constriction following administration of both oxycodone and buprenorphine buccal film. Methods: Healthy individuals who self-identified as recreational opioid users were recruited. Effects of study treatments (placebo; 300 μg, 600 μg, and 900 μg buprenorphine buccal film; and 30 mg and 60 mg oral oxycodone, separated by 7-day washouts) were compared using a randomized, double-blind, double-dummy, 6-treatment, 6-period, placebo-controlled crossover design. Pearson's r correlation coefficients were calculated for the change from baseline in minute ventilation versus the change from baseline in pupil size for each treatment. An institutional review board approved the study protocol. Results: A total of 19 subjects were enrolled; 15 subjects completed the study. During treatment with buprenorphine buccal film or oxycodone, change from baseline in minute ventilation was moderately correlated with change from baseline in pupil diameter (r=0.34-0.40; P≤0.005). Miosis was noted for both drugs, with statistically significant effects occurring earlier for oxycodone than for buprenorphine buccal film. Conclusions: Pupil diameter was moderately correlated with respiratory drive for buprenorphine buccal film and oxycodone treatments, and previous studies have illustrated a relationship between pupil constriction and drug liking.1,2 The decrease in pupil diameter associated with opioid administration occurred later following buprenorphine buccal film administration (compared with oxycodone), which may translate to a decreased risk of drug liking.