A Phase 1, randomized, open-label crossover study to evaluate the safety and pharmacokinetics of 400 mg albaconazole administered to healthy participants as a tablet formulation versus a capsule formulation

Abstract

Background: Albaconazole is a novel triazole being developed for the oral treatment of fungal diseases. Once-weekly oral dosing with 400 mg albaconazole for 24 or 36 weeks resulted in high rates of clinical and mycological resolution for distal subungual onychomycosis, as well as a favorable safety and tolerability profile.

Purpose: To compare four 100-mg albaconazole capsules to one 400-mg albaconazole tablet for bioavailability, bioequivalence, tolerability, and safety.

Patients and methods: Forty participants were enrolled in this Phase I, open-label, two-sequence crossover study. Twenty participants were exposed to a single 400-mg tablet dose of albaconazole before being crossed over to a single dose of four 100-mg albaconazole capsules. The second group of 20 participants received the study products in reverse order. Blood samples were taken over 15 days post-dose to assess the plasma concentrations and pharmacokinetic parameters of albaconazole and its primary metabolite, 6-hydroxyalbaconazole. Safety was assessed throughout the study.

Results: The area under the curve (AUC) and maximum measured plasma concentration (C(max)) of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the C(max) but not for the AUC measurements (AUC(0-t) and AUC(0-inf)). Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%-125% range for both the C(max) and AUC, we concluded that the formulations were not bioequivalent with respect to the rate or extent of absorption. Both formulations were safe and well-tolerated in this study. All adverse events (AEs) were generally mild and were mainly gastrointestinal- or nervous system-related (eg, dizziness, headache). No electrocardiogram findings were reported as an AE, and no serious AEs or deaths were reported.

Conclusion: The AUC and C(max) of albaconazole after a single 400-mg oral dose administered as a tablet formulation were lower than those of a capsule formulation. Albaconazole tablets and capsules cannot, therefore, be considered bioequivalent.

Keywords: albaconazole; onychomycosis; pharmacokinetics; triazole.

Figures

Figure 1

Schematic of the study design.

Figure 2

Mean albaconazole (A) and 6-hydroxyalbaconazole (B) plasma concentrations versus time curves for all participants (PK analysis set).