Comparison of the Safety, Tolerability, and Pharmacokinetics of Fidaxomicin in Healthy Japanese and Caucasian Subjects

Background and Objectives Fidaxomicin treatment of Clostridium difficile infection is known to produce minimal systemic exposure, as the antibacterial (antibiotic) remains primarily in the gut. In this randomized, double-blind, placebo-controlled study, the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of fidaxomicin were evaluated in healthy Japanese and Caucasian subjects. Methods Thirty-six healthy subjects were randomly assigned in a 3:1 ratio to receive either fidaxomicin or placebo. Cohort 1 (100 mg) and Cohort 2 (200 mg) comprised 12 Japanese subjects each and Cohort 3 (200 mg) comprised 12 Caucasian subjects. Subjects received a single dose of the study drug on Day 1 and received multiple doses for 10 days after a wash-out period. Results After multiple 200 mg dosing of fidaxomicin, both mean maximum plasma concentrations ( C max ) in Japanese (8.7 ± 5.3 ng/mL) and Caucasian (7.0 ± 3.7 ng/mL) subjects and the area under the concentration–time curve (AUC) were higher in Japanese subjects (58.5 ± 36.7 ng·h/mL) than in Caucasian subjects (37.6 ± 15.7 ng·h/mL), although variation in both groups was large. The mean fecal concentrations of fidaxomicin in Japanese and Caucasian subjects were 2669 and 2181 μg/g, respectively. The possibly study drug-related adverse events were diarrhea ( n = 1), feeling hot ( n = 1), and hypersomnia ( n = 2), which were mild in severity. Conclusions In both Japanese and Caucasian subjects, fidaxomicin demonstrated similarly minimal systemic absorption, and was mainly excreted in feces. Fidaxomicin was safe and well-tolerated in all subjects.