Original Abstract

AIMS: To evaluate the bioequivalence of orally administered orforglipron tablets and capsules in participants with obesity or overweight who were otherwise healthy. MATERIALS AND METHODS: This phase 1, multicenter, open-label, multiple-dose, dose-escalation study was conducted in 429 healthy adults. Study participants received each orforglipron capsule and tablet dose strength once daily for 7 days in the fasted state at capsule doses of 1, 3, 6, 12, 24, or 36 mg and corresponding tablet doses of 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg. The primary endpoint was steady-state area under the concentration-time curve from 0 to 24 h (AUC0-24,ss) and steady-state maximum observed drug concentration (Cmax,ss). A prespecified mixed scaling approach was applied to evaluate bioequivalence. Safety and tolerability of the tablets and capsules were also assessed. RESULTS: Bioequivalence was demonstrated between capsules and dose-adjusted tablets across all six doses. The 90% confidence interval of the ratios of the geometric least-squares means of AUC0-24,ss and Cmax,ss between each capsule dose and corresponding tablet dose met the predefined criteria for bioequivalence. The safety profiles were similar between tablets and capsules, with no apparent differences or trends in the incidence of treatment-emergent adverse events by presentation or with increasing dose. CONCLUSIONS: Once-daily orforglipron capsules and dose-adjusted tablets demonstrated pharmacokinetic bioequivalence at all tested doses and showed similar safety and tolerability profiles, with mostly mild treatment-emergent adverse events consistent with previous orforglipron clinical trials. CLINICALTRIALS: gov Identifier: NCT06440980.