Журнал биоэквивалентности и биодоступности

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Bioequivalence Study of a Novel Clobetasol Propionate Topical gel 0.05% using the Vasoconstriction Bioassay

Catherine Queille-Roussel, Francesca Morano, Andrea F D Di Stefano, Paola Babbi, Massimiliano Perego

Background: A novel propylene glycol-based gel containing Clobetasol propionate 0.05% was developed.

Methods: This phase I single center, randomized, reference-controlled, human skin vasoconstriction assay study was subdivided into 2 parts with the aim of comparing the skin blanching effect of the new Clobetasol gel versus a marketed reference cream to test their in vivo bioequivalence in compliance with FDA guidance. The pilot part determined the dose-duration response curve to the reference. The pivotal part was the pharmacodynamics in vivo bioequivalence study. Healthy volunteers received single applications on randomized sites of the forearms. In the pilot part, the reference was applied once at 8 dose durations from 0.25 to 6 h to determine the dose duration (D) at which effect is half-maximal (ED₅₀). In the pivotal part, 3 dose durations were used (ED₅₀, D₁ ≈ ½ ED₅₀, D₂ ≈ 2ED₅₀). Test and reference were applied once at the ED₅₀ dose duration each to 2 sites per forearm. Untreated sites acted as negative controls. Skin blanching was measured using a chromameter. The colorimetric a* variable was analyzed over time (0-24 h after product removal).

Results: In the pilot part, ED₅₀=0.52 h was defined in 12 Caucasian responders. Ninety (90) responders were enrolled in the pivotal part and 40 met the detector criterion requested for bioequivalence. a*, analyzed using Locke’s method, gave 90% confidence interval of the test/reference ratio corresponding to 88.6%-101.7% (acceptance criteria: 80%-125%).

Conclusion: The test gel was bioequivalent to the reference. Registered at Clinicaltrialsregister.eu with the EudraCT number 2018-001640-59 on 27JUL2018.