Clobetasol propionate foam 0.05%: a novel vehicle with enhanced delivery

ABSTRACT

One hundred and eighty-eight subjects with psoriasis of the scalp voluntarily participated in this multicenter, randomized, double-blind, active, and placebo-controlled study to evaluate the safety and efficacy of clobetasol propionate foam 0.05% (CP foam) relative to clobetasol propionate solution 0.05% (CP solution, Temovate^® scalp application). Adult male and female subjects with moderate to severe disease were assigned to one of four treatment groups in a 2 : 1 : 2 : 1 ratio (CP foam : placebo foam : CP solution : placebo solution). Moderate to severe disease was defined as involvement of at least 10% of the scalp and a minimum score of 2 (0, none; 1, mild; 2, moderate; 3, severe; 4, very severe) for each of the primary signs of psoriasis (erythema, scaling, plaque thickness).

Subjects applied study medication to the entire scalp twice daily for 14 consecutive days and were required to use DHS shampoo. No other therapy to the scalp was allowed. Pruritus, scaling, erythema, and plaque thickness were evaluated on days 0, 7, and 15, and after 2 weeks off treatment on day 28. In addition, both the investigator and subject evaluated the global response to treatment at days 15 and 28 using a seven-point grading scale (completely clear, almost clear, marked improvement, moderate improvement, slight improvement, no change, or worse). The number of subjects who were ''completely clear'' or ''almost clear'' (> 90% clearing) were lumped together to determine treatment success. Safety was assessed via standard clinical laboratory panels (chemistry, hematology, urinalysis), physical examination, vital signs, and reported adverse events.

In addition to the clinical study, the potency of CP foam relative to five other dosage forms of CP, as well as to betamethasone valerate lotion 0.1%, was determined in 24 healthy male and female subjects using a modification of the new vasoconstrictor procedure. ¹Products were randomly applied to 3.14 cm ²sites on the ventral forearms at a dose of 10 μL, covered with a nonocclusive guard, then removed after 3 h with dry, cotton swabs. Skin color was measured at − 1, 1, 4, 8, 12, 24, and 30 h using a chromameter (Minolta, Ramsey, NJ). Vasoconstrictor potency was assessed from the area-under-the-skin-blanching curve (AUC) using the a* scale output of the chromameter.

The percutaneous absorption of CP from both the foam and solution formulations was determined using the cadaver skin assay. ²Each product was applied to multiple sections of skin at a dose of 6–8 mg/cm ², and the solution bathing the dermis was sampled at intervals and analyzed for CP content by high performance liquid chromatography.

Investigators: Edwin A. Bronsky, md, Intermountain Clinical Research, Salt Lake City, UT; Frank E. Dunlap, md, Argus Research, Inc., Tuscon, AZ; Holly B. Faust, md, Indiana University, Indianapolis, IN; David P. Fivenson, md, Henry Ford Hospital, Detroit, MI; Alan M. Heller, md, San Jose Clinical Research, San Jose, CA; Paul A. Lehman, MS, University of Arkansas for Medical Sciences, Little Rock, AR; Dale E. Martin, md, Skin Surgery and Skin Tumor Medical Group of San Diego, San Diego, CA; Bruce H. Miller, md, Dermatology Associates Research Center, Portland, OR; S. David Miller, md, New England Research Center, North Dartmouth, MA; Jennie J. Muglia, md, Rhode Island Hospital, Providence, RI; Toivo E. Rist, md, Dermatology Associates of Knoxville, Knoxville, TN; Ronald C. Savin, md, Savin Dermatology Center, New Haven, CT; Linda F. Stein, md, Henry Ford Hospital, Detroit, MI; Kenneth J. Washenik, md, ph d, NYU Medical Center, New York, NY