Clobetasol propionate 0.05% lotion in the treatment of moderate to severe atopic dermatitis: a randomized evaluation versus clobetasol propionate emollient cream

Journal of Drugs in Dermatology, May-June, 2005 by Debra Breneman, Alan B. Fleischer, Jr., David Kaplan, Mark Lebwohl, Bruce Miller, David Pariser, Toivo Rist, L. Swinyer, Yin Liu, Valerie Foley

Safety was monitored by assessing telangiectasia and skin atrophy, concomitant therapies and adverse events (AEs). Skin atrophy and telangiectasia were scored on a 0 (none) to 3 (severe) scale at all application sites.

Statistics

To detect with a 90% power a difference of 1 point in mean DSS score, the primary efficacy variable between the 2 active treatments by a 2-sided t-test with [alpha] = 0.05, a sample of 168 evaluable subjects at least (84 per group) was needed.

To compare the lotion with its vehicle, a significant difference was needed for both primary efficacy variables; therefore, a power of 95% was needed for each variable separately to provide a 90% power of finding a significant difference on both. A total enrollment of 224 subjects (approximately 96 per active treatment, 32 for the vehicle) was planned, accounting for the anticipated subject ineligibility (10% to 15%) for efficacy at week 2 and the designed randomization ratio of 3:3:1 for the 2 active treatment groups and the vehicle group, respectively.

Clobetasol propionate lotion was compared to its vehicle to demonstrate superior efficacy. Comparisons between clobetasol propionate lotion and clobetasol propionate emollient cream were conducted to demonstrate non-inferiority.

Results

Subjects

A total of 229 subjects were randomized and treated: 96 received clobetasol propionate lotion, 100 received clobetasol propionate emollient cream and 33 received lotion vehicle. A total of 205 subjects in the ITT population completed 2 weeks of treatment with study medication. One subject treated with clobetasol propionate lotion had the disease condition cleared after 1 week of treatment and, therefore, entered the treatment-free period early.

Twenty-three subjects discontinued from the study: nine (9.4%) subjects receiving clobetasol propionate lotion, 7 (7.0%) subjects receiving clobetasol propionate emollient cream, and 7 (21.2%) subjects receiving lotion vehicle. Subject request and loss to follow-up were the major reasons for discontinuation in each treatment group. In the lotion vehicle group, one subject discontinued due to an adverse event (worsening of AD), and one was discontinued due to protocol deviation for over use of study medication.

Baseline demographics are shown in Table 1. There were no significant differences reported in disease characteristics among the treatment groups (p > .05).

Efficacy

At week 2 end point (LOCF) the proportion of subjects who achieved "success" was significantly higher in the lotion group compared to the vehicle group (72.9% vs. 36.4%; p = .001) there was no difference between the active treatments (72.9% vs. 74.0%) (Figure 1). At all other time points, success rates for the lotion group were statistically significantly higher than for the vehicle group (p < .05), and were non-inferior to the emollient cream group (p > .05). After the 2-week treatment-free period, success rates for both the lotion and cream groups remained significantly higher relative to those observed in the lotion vehicle group, with a success rate decreasing by 14.5% in the clobetasol propionate lotion group as compared to an 18.0% decrease in the cream group.

At week 2 the full-scale GSS for the lotion group was significantly lower than that for the vehicle group (p = .001); there was no difference between the 2 clobetasol propionate formulations. Statistically significant differences at week 1 and week 4/follow-up were observed between the lotion group and its vehicle group (p < .05) for the GSS, whereas it was comparable in both active treatment groups.