Pharmacokinetics, safety, and tolerability of an oxfendazole tablet formulation: a phase 1, randomized, placebo-controlled trial in healthy African volunteers.

Oxfendazole, a registered veterinary drug, has demonstrated broad-spectrum activity against multiple nematode species. First-in-human studies in healthy, predominantly Caucasian adults receiving a liquid formulation of oxfendazole demonstrated a favorable pharmacokinetic and safety profile, supporting its potential as a drug candidate for treating human helminth infections. To further advance its clinical development, we conducted a phase I bioavailability study using a field-applicable, immediate-release oxfendazole tablet. This trial investigated the pharmacokinetics, safety, and tolerability of the tablet formulation in healthy African adults residing in a filariasis-endemic country. Oxfendazole was administered as a single dose (100 or 400 mg) or as multiple doses (400 mg for 5 consecutive days) to 30 participants, randomized 8:2 to oxfendazole or placebo per cohort. Plasma concentrations of oxfendazole were measured using a validated high-performance liquid chromatography tandem mass spectrometry method, and pharmacokinetics were assessed using non-compartmental analysis. Peak plasma concentrations were reached after ~2.5-3 h. The median elimination half-life ranged from 11.6 to 13.9 h and was consistent across cohorts. Non-linear pharmacokinetics was observed, with exposure (AUC∞, Cmax) increasing less than dose-proportionally and showing high variability. Oxfendazole was well tolerated, with no adverse events reported and no clinically significant abnormalities in laboratory tests, vital signs, physical examinations, or electrocardiograms. These findings support the further development of oxfendazole in early proof-of-concept studies. Formulation optimization is suggested to reduce variability in exposure and improve the reliability of exposure-response assessments in future clinical trials.The study is registered with ClinicalTrials.gov as NCT04920292.