Two Multicenter, Randomized, Double-Blind, Parallel Group Comparison Studies of a Novel Foam Formulation of Halobetasol Propionate, 0.05% vs Its Vehicle in Adult Subjects With Plaque Psoriasis

BACKGROUND: A novel foam formulation of halobetasol propionate, 0.05% (HBP-Foam) has been developed to treat plaque psoriasis in patients who prefer a thermostable topical foam with low application shear that allows for easier coverage over large and/or hirsute areas than existing formulations. OBJECTIVE: To determine the safety and effectiveness of HBP-Foam in subjects with plaque psoriasis. METHODS: Two randomized, double-blind, vehicle-controlled clinical studies were conducted in 560 adult subjects with moderate to severe plaque psoriasis. Subjects applied the assigned test article to all psoriatic plaques twice daily for 14 days. The key efficacy measures were the proportion of subjects with "treatment success," defined as those subjects that achieved a score of 0 (clear) or 1 (almost clear) and at least a two-grade improvement compared to baseline for the Investigator's Global Assessment (IGA) and for the clinical signs of psoriasis (plaque elevation, scaling, and erythema) as well as pruritus. Safety measurements included adverse events and local skin reactions in the treatment area. RESULTS: HBP-Foam was statistically superior to vehicle in achieving "Treatment Success" in 25.3% and 30.7% vs 3.9% and 7.4% (P<0.001) in Studies 1 and 2, respectively. Pruritus scores statistically improved by over 30% in HBP-Foam treated subjects. In addition, these subjects experienced a significant reduction in the clinical signs of psoriasis (plaque elevation, scaling, and erythema). In contrast, in the vehicle groups the decrease in psoriasis-related signs was generally not observed. Safety outcomes were unremarkable and similar in both the HBP-Foam and vehicle treatment groups. CONCLUSIONS: These results demonstrate the safety and effectiveness of HBP-Foam in the treatment of plaque psoriasis. Furthermore, this novel foam formulation has demonstrable for its ease of application over large and/or hairy treatment areas. ClinicalTrials.gov Registration: NCT02742441 NCT02368210

Pharmacokinetics and Bioequivalence of Branded and Generic Formulations of Dofetilide 0.5-mg Capsules After Single-Dose Administration in Healthy Subjects.

Class III antiarrhythmics are preferred therapy for managing atrial fibrillation/flutter. Dofetilide 0.5-mg capsules were US Food and Drug Administration (FDA) approved in 1999 to treat atrial fibrillation/flutter. Bioequivalence of generic dofetilide is important for treating arrhythmias because drug concentrations must be consistent to maintain normal sinus rhythm. Generic dofetilide 0.5-mg capsule pharmacokinetics were compared with branded product in 2 open-label, 2-way crossover, single-dose studies - 1 study each in fasted and fed healthy subjects. Blood samples were collected before and up to 48 hours after dosing. Safety was assessed by tabulating adverse events and vital signs. Seventy-three subjects were enrolled; 59 completed the studies. In fasted subjects, the 90% confidence intervals (CIs) for generic dofetilide 0.5 mg versus the reference formulation were 0.996-1.026 for the area under the plasma concentration-time curve from 0 to infinity (AUC) and 0.974-1.066 for the maximum observed concentration (Cmax ). In fed subjects, the 90%CIs for AUC and Cmax were 0.988-1.015 and 0.928-0.992, respectively. All ratios were within the FDA-established bioequivalence range. Twenty-six subjects experienced 37 adverse events (generic, 15; reference, 22); all but 1 were mild or moderate in severity. Generic dofetilide 0.5-mg capsules can be considered bioequivalent to the reference product.