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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| Format: | Article |
| Language: | English |
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Dove Medical Press
2013-01-01
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| Series: | Clinical Pharmacology: Advances and Applications |
| Online Access: | http://www.dovepress.com/a-phase-1-randomized-open-label-crossover-study-to-evaluate-the-safety-a12086 |
| _version_ | 1818997087219482624 |
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| author | van Rossem K Lowe JA |
| author_facet | van Rossem K Lowe JA |
| author_sort | van Rossem K |
| collection | DOAJ |
| 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%–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 |
| first_indexed | 2024-12-20T21:40:03Z |
| format | Article |
| id | doaj.art-4a4327f988d34ca295ed2980f6fa1cd3 |
| institution | Directory Open Access Journal |
| issn | 1179-1438 |
| language | English |
| last_indexed | 2024-12-20T21:40:03Z |
| publishDate | 2013-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Pharmacology: Advances and Applications |
| spelling | doaj.art-4a4327f988d34ca295ed2980f6fa1cd32022-12-21T19:25:50ZengDove Medical PressClinical Pharmacology: Advances and Applications1179-14382013-01-012013Issue 12331A 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 formulationvan Rossem KLowe JAKoen 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%–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, onychomycosishttp://www.dovepress.com/a-phase-1-randomized-open-label-crossover-study-to-evaluate-the-safety-a12086 |
| spellingShingle | 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 Clinical Pharmacology: Advances and Applications |
| 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_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_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_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 |
| url | http://www.dovepress.com/a-phase-1-randomized-open-label-crossover-study-to-evaluate-the-safety-a12086 |
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