Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open Label Phase 1 Multiple Ascending Dose and Food Effect Study

Neurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human use, Phase I multiple ascending dose and food effect studies were conducted. Thirty-six healthy adults were enrolled in an open label study which evaluated 1) the pharmacokinetics and safety of oxfendazole following multiple ascending doses of oxfendazole oral suspension at 3, 7.5 and 15 mg/kg once daily for 5 days and 2) the effect of food on oxfendazole pharmacokinetics and safety after a single 3 mg/kg dose administered following an overnight fast or the consumption of a fatty breakfast. Following multiple oral dose administration, the intestinal absorption of oxfendazole was rapid with Tmax ranging from 2.02 to 2.56 hours. A similar half-life of oxfendazole (9.21 to 11.8 hours) was observed across all dose groups evaluated, and oxfendazole exhibited significantly less than dose-proportional increase in exposure. Oxfendazole plasma exposures were higher in female subjects than in male subjects. Following daily administration, oxfendazole reached a steady state in plasma on Study Day 3, with minimal accumulation. Food delayed oxfendazole Tmax by a median of 6.88 hours and resulted in a 49.2% increase in Cmax and 86.4% increase in AUC. Oxfendazole was well tolerated in all study groups, and there were no major safety signals identified in this study.