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

Koen van Rossem,1 Jenny A Lowe21Stiefel, Research Triangle Park, NC, USA; 2Stiefel, Stockley Park West, Uxbridge, UKBackground: 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...

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Autores principales:	van Rossem K, Lowe JA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/4a4327f988d34ca295ed2980f6fa1cd3
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spelling	oai:doaj.org-article:4a4327f988d34ca295ed2980f6fa1cd32021-12-02T07:06:50ZA 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 formulation1179-1438https://doaj.org/article/4a4327f988d34ca295ed2980f6fa1cd32013-01-01T00:00:00Zhttp://www.dovepress.com/a-phase-1-randomized-open-label-crossover-study-to-evaluate-the-safety-a12086https://doaj.org/toc/1179-1438Koen van Rossem,1 Jenny A Lowe21Stiefel, Research Triangle Park, NC, USA; 2Stiefel, Stockley Park West, Uxbridge, UKBackground: 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 (Cmax) of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the Cmax but not for the AUC measurements (AUC0-t and AUC0-inf). Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%&ndash;125% range for both the Cmax 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 Cmax 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, triazole, pharmacokinetics, onychomycosisvan Rossem KLowe JADove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2013, Iss Issue 1, Pp 23-31 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 van Rossem K Lowe JA 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
description	Koen van Rossem,1 Jenny A Lowe21Stiefel, Research Triangle Park, NC, USA; 2Stiefel, Stockley Park West, Uxbridge, UKBackground: 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 (Cmax) of the albaconazole tablet were approximately 10% and 22% lower, respectively, than for the albaconazole capsules. Statistical significance was reached for the Cmax but not for the AUC measurements (AUC0-t and AUC0-inf). Because the 90% confidence intervals based on the differences between the tablet and capsule were outside the 80%&ndash;125% range for both the Cmax 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 Cmax 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, triazole, pharmacokinetics, onychomycosis
format	article
author	van Rossem K Lowe JA
author_facet	van Rossem K Lowe JA
author_sort	van Rossem K
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/4a4327f988d34ca295ed2980f6fa1cd3
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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

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