Repurposing Oxfendazole for Onchocerciasis: Population Pharmacokinetics of a Tablet Formulation in Healthy African Adults

ABSTRACT Global efforts to eliminate onchocerciasis are hampered by the lack of a macrofilaricidal drug capable of killing adult parasites. Oxfendazole, a veterinary anthelminthic, exhibits macrofilaricidal activity and holds promise to shorten treatment durations. Phase 1 studies in healthy Caucasian adults demonstrated favorable pharmacokinetics and safety using a veterinary oral liquid formulation. More recently, a Phase 1 bioavailability trial (NCT04920292) evaluated a field‐applicable tablet formulation in healthy African adults. This study presents a secondary analysis to (i) characterize the population pharmacokinetics of oxfendazole and its major metabolites in healthy African adults receiving the tablet formulation and (ii) propose a dosing regimen for Phase 2 evaluation in patients with onchocerciasis. Thirty healthy African adults were enrolled, and plasma concentration–time profiles of oxfendazole, fenbendazole, and oxfendazole sulfone were obtained from 24 participants who received oxfendazole (8 per dose group: 100 mg single dose, 400 mg single dose, 400 mg once daily for 5 days). All cohorts were pooled and analyzed using nonlinear mixed effects modeling. Oxfendazole absorption was best described by first‐order kinetics with first‐pass metabolism. Dose‐limited bioavailability was evident. Disposition was best described by one‐compartment models with linear elimination. Simulations suggested that 400 mg once daily (or 50 mg twice daily) for 5 days is required to achieve putative exposure targets (> 200 ng/mL for 5 days), with low risk of safety concerns. The population pharmacokinetic model adequately described oxfendazole pharmacokinetics in healthy African adults and supports dosing selection for future clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04920292