title: A randomized, double-blind, multiple-dose, placebo-controlled, dose escalation study with a 3-cohort parallel group design to investigate the tolerability and pharmacokinetics of albaconazole in healthy subjects.
abstract: Albaconazole is a triazole antifungal agent discovered at Palau Pharma SA (Barcelona, Spain) and currently being developed for the treatment of fungal infections of the nails. This randomized, double-blind, placebo-controlled, phase 1 study evaluated the safety, tolerability, pharmacokinetics, and effects on electrocardiogram parameters of albaconazole administered orally at escalating supratherapeutic doses. Healthy subjects received 400 mg albaconazole every 24, 12, or 8 hours for 5 days. Albaconazole was absorbed rapidly (2.5-22.5 hours) after oral administration, reaching a maximal mean peak plasma concentration of 11,993.3 ng/mL (standard deviation [SD], 2,413.85 ng/mL) after 5 days of dosing every 8 hours. Systemic exposure of albaconazole increased proportionally with dose frequency. Albaconazole was safe and well tolerated at all doses administered. No significant changes in ECG intervals or morphology were observed. In none of the three dosing groups was the slope of a study-specific correction for QT interval (QTcSS) on log plasma concentration statistically different from 0. The results of this study were to be used to inform the design of a thorough QT study using supratherapeutic doses. A dose regimen of 400 mg, every 8 hours for 5 days appears suitable for this purpose.
authors.affiliation: Spaulding Clinical Research, LLC, West Bend, WI, USA.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Dietz
authors.affiliation: Stiefel, A GSK Company, Uxbridge, Middlesex, UK.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Barnard
authors.affiliation: Stiefel, A GSK Company, Research Triangle Park, NC, USA.
authors.forename: Koen
authors.initials: K
authors.lastname: van Rossem
keywords: QTc; albaconazole; onychomycosis; pharmacokinetics; supratherapeutic dose