A Randomized, Parallel Group, Open Label, Multicenter Study to Assess the Potential for Adrenal Suppression and Systemic Drug Absorption Following Multiple Dosing with Clobetasol Propionate Cream (Impoyz™), 0.025% versus Clobetasol Propionate (Temovate®)

Abstract

Importance: Topical corticosteroids continue to play an important role in therapy for individuals with moderate-to-severe psoriasis, particularly in cases where systemic therapy is contraindicated or in which combination topical-systemic therapy is needed to achieve desired results. Although super-high-potency corticosteroids such as clobetasol propionate have the potential to produce desired results, side effects related to systemic absorption may limit their clinical utility. Objectives: To evaluate the potential of a new, lower-concentration clobetasol propionate cream 0. 025% (Impoyz Cream, [IMP]) to suppress the hypothalamic-pituitary-adrenal (HPA) axis as compared to clobetasol propionate, 0.05% cream (Temovate Cream, [TMV]) under maximal use conditions in patients with moderate-to-severe plaque psoriasis. To compare the plasma concentrations of clobetasol propionate before and after 2 weeks of topical treatment with either IMP Cream or TMV Cream under maximal use conditions.Design, Setting, and Participants: Randomized, multi-center, open-label study conducted across 15 clinical sites in the United States. Eligible subjects were males or females, at least 18 years old, with a clinical diagnosis of stable (at least 3 months) plaque-type psoriasis that involved 20% to 50% of the body surface area (BSA). 50 patients with an Investigator Global Assessment (IGA) grade of at least 3 (moderate) at Baseline were randomized (1:1) to twice daily treatment with either IMP Cream or TMV Cream for 15 consecutive days.Main Outcomes and Measures: Primary safety assessments included hypothalamic-pituitary-adrenal axis suppression (as measured by ACTH stimulation test) and systemic drug absorption (as measured by plasma clobetasol propionate levels drawn at baseline and on Day 15 of treatment at 0, 1, 3, and 6 hours after final study product application). Secondary safety assessments included serum DHEAS at Days 8 and 15 and local cutaneous adverse events. The primary efficacy assessment was Investigator Global Assessment (IGA) score, measured at Days 8 and 15 of treatment.Results: Upon conclusion of the treatment period, the mean serum concentration of clobetasol propionate was significantly lower in the IMP Cream group vs the TMV group (56.3 vs 152.5 pg/mL, p=0.014). A lower proportion of subjects in the IMP group experienced HPA-axis suppression compared to the TMV group, although this did not reach statistical significance (12.5% vs 36.4%, p=0.086). In terms of efficacy, the two treatment groups displayed similar marked improvement in psoriasis severity after 15 days of treatment, with 50% of the subjects in each group having an IGA score of 2 (mild) and 16.7% in the IMP group and 18.1% in the TMV group having a score of 0 or 1 (none or minimal). Conclusions and Relevance: Subjects with moderate-to-severe plaque psoriasis treated with a 15 day course of IMP Cream demonstrate lower levels of plasma clobetasol propionate than those treated with TMV, suggesting lower levels of systemic corticosteroid exposure with IMP versus those with TMV. Additionally, in this sample, topical therapy with IMP was associated with a trend towards a lower incidence of HPA axis suppression than TMV without comprising efficacy. Trial Registration: Registered 6 May, 2014.