A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle Controlled Clinical Study to Assess the Safety and Efficacy of a Halobetasol/Tazarotene Fixed Combination in the Treatment of Plaque Psoriasis
March 2017 | Volume 16 | Issue 3 | Original Article | 197 | Copyright © March 2017
Jeffrey L. Sugarman MD PhD,a Linda Stein Gold MD,b Mark G. Lebwohl MD,c David M. Pariser MD,d Binu J. Alexander MD,e and Radhakrishnan Pillai PhDf
aUniversity of California, San Francisco, CA bHenry Ford Hospital, Detroit, MI cIcahn School of Medicine at Mount Sinai, New York, NY dVirginia Clinical Research, Inc., Norfolk, VA eValeant Pharmaceuticals, North America, LLC, Bridgewater, NJ fDow Pharmaceutical Sciences Inc. (a division of Valeant Pharmaceuticals, North America LLC), Petaluma, CA
Abstract
BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. Topical corticosteroids are the mainstay of treatment, however long-term safety remains a concern, particularly with the more potent formulations. Combination therapy with a corticosteroid and tazarotene may improve psoriasis signs at a lower corticosteroid concentration providing a superior safety profile. OBJECTIVE: To investigate the efficacy and safety of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its monads and vehicle in subjects with moderate-to-severe plaque psoriasis. METHODS: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Subjects randomized (2:2:2:1 ratio) to receive HP/TAZ, individual monads, or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of ‘Clear’ or 'Almost Clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion. Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as 2 weeks. At week 8, 52.5% of subjects had treatment success compared with 33.3%, 18.6%, and 9.7% in the HP (P=0.033), TAZ (P less than 0.001), and vehicle (P less than 0.001) groups, respectively. HP/TAZ lotion was superior to its monads and vehicle in reducing the psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. At week 8, a 2-grade improvement in IGA was achieved by 54.2% of subjects for erythema, 67.8% for plaque elevation, and 64.4% for scaling. Most frequently reported TEAEs were application site reactions, and were more likely associated with the tazarotene component. Side effects such as skin atrophy were rare. CONCLUSIONS: HP/TAZ lotion was consistently more effective than its monads or vehicle in achieving treatment success and reducing psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. Safety data were consistent with the known safety profile of halobetasol propionate and tazarotene, and did not reveal any new safety concerns with the combination product.
J Drugs Dermatol. 2017;16(3):197-204.
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INTRODUCTION
Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression and affects approximately 2% of the population.1-3 Treatment options focus on relieving symptoms, reducing in ammation, induration, and scaling, and controlling the extent of the disease. Many sufferers have localized disease where topical therapy can provide the cornerstone of treatment.4Topical treatments are first-line therapies for the majority of patients since approximately 80% of the patients have mild or moderate psoriasis (defined as <10% body surface area [BSA] involvement).5 Use of topical corticosteroids is commonplace; however, long-term safety remains a concern, particularly with the more potent formulations with increased risk of local cutaneous adverse events (AEs), including skin atrophy, and infrequently, adrenal suppression.5-7 Combination therapy may also increase the duration of treatment benefit as well as length of remission.8 Tazarotene has been shown to be an effective treatment for psoriasis.9 Use of topical tazarotene is limited by its potential
