Short-term safety assessment of clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis

Journal of Drugs in Dermatology, April, 2006 by Philippe Andres, Michel Poncet, Farzaneh Sidou, Pascale Soto

Atrophogenicity was monitored at the edge of the scalp at baseline and at 2 and 4 weeks using a B-scan ultrasound device (Dermascan C, Cortex Technology, Denmark). The probe and transducer were 20 MHz. A gelatine plug was applied to the skin and the probe was placed perpendicularly to the skin application with pressure being maintained as lightly as possible. The measurements were carried out on 3 different test sites on the forehead, previously delineated at the baseline visit; results were averaged. Epidermis plus dermis thickness, expressed in millimeters were assessed.

Ophthalmologic outcome measures were intraocular pressure (IOP, measured by the Goldman method), results of slit lamp examination, and visual acuity assessment (Parinaud scale for near visual acuity and Monoyer scale for far visual acuity). Subjects were asked to rate burning or stinging sensation in the eyes after applying the test product on a scale from 0 (absent) to 3 (severe). Finally, the investigator provided an overall summary of the ocular tolerability for each subject as a binary outcome of acceptable or not acceptable.

Efficacy was assessed by the DSS, defined as the sum of erythema, adherent desquamation, and plaque thickening on a score from 0 (none) to 3 (severe) with half point ratings being allowed.

Statistical Methods

For this exploratory safety study, a sample size of at least 12 subjects per group was considered appropriate to assess the HPA axis suppression potential of clobetasol propionate shampoo or gel.

Serum cortisol concentrations were analyzed by evaluation of covariance (ANCOVA), with baseline as the covariate and treatment group as factor. Separate analyses were done for pre-stimulation and post-stimulation values and for the change on stimulation. Skin thickness was analyzed using an ANCOVA model with the baseline value as a covariate. Ocular safety variables were analyzed with the Cochran-Mantel-Haenszel (CMH) test, using the ridit transformation. Differences of the DSS between the treatments were assessed in an ANCOVA model, adjusting for baseline scores.

Results

Subjects Studied

Twenty-five of the 26 enrolled subjects completed the study. The treatment groups matched well at baseline for age, but there were more females in the clobetasol propionate gel group than in the clobetasol propionate shampoo group and symptom severity and extent of involvement at baseline were worse in the clobetasol propionate shampoo group than in the clobetasol propionate gel group (Table 1). Compliance checking showed that the actual use of the study treatments was in good agreement with the specified dosing schedule.

Safety

HPA Axis Suppression

Two out of 12 subjects (16%) in the clobetasol propionate gel group were suppressed according to the following definition for HPA axis suppression: subjects with a pre-stimulation value of cortisol below the normal range of 7[micro]g/dl, and/or a post-stimulation value lower than 20[micro]g/dl were considered to be suppressed. Values of pre- and post-stimulation are provided in Table 2.