OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study - 20/07/16
, Lawrence F. Eichenfield, MD gAbstract |
Background |
Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B.
Objectives |
We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD.
Methods |
This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks.
Results |
The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity.
Limitations |
Further confirmatory phase-III studies are required.
Conclusion |
OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.
Le texte complet de cet article est disponible en PDF.Key words : atopic dermatitis, atopic eczema, OPA-15406, phosphodiesterase type 4 inhibitor, topical agents, topical calcineurin inhibitor
Abbreviations used : AD, BSA, DLQI, EASI, IGA, IL, PDE4, VAS
Plan
| Supported by Otsuka Pharmaceutical Development and Commercialization Inc, Rockville, MD. |
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| Disclosure: Dr Hanifin served as a consultant to Anacor Pharmaceutical, Dermira, Leo Pharma, and Otsuka Pharmaceuticals and participated in studies in recent years for Pfizer, Merck, Chugai Pharmaceutical, and Anacor Pharmaceuticals. Dr Ellis served as a consultant to Celgene Corporation, Ferndale Healthcare, Johnson & Johnson, and Otsuka Pharmaceutical. Dr Frieden serves as the chair of the data and safety monitoring board for this OPA-15406 phase-II study, is an advisor for Galderma SA and Anacor Pharmaceuticals, and is a consultant with Laboratoires Pierre Fabre. Dr Fölster-Holst participated in studies in recent years for Novartis International AG, Astellas Pharma, Laboratoires Pierre Fabre, Regeneron Pharmaceuticals, and Pharmanet AG; delivered presentations for La Roche–Posay, ALK, Abbott Laboratories, and Neubourg GmbH; served on an advisory board for Johnson & Johnson; and is a member of the data and safety monitoring board for this OPA-15406 phase-II study. Dr Stein Gold is a member of the data and safety monitoring board for this OPA-15406 phase-II study and is an advisor and investigator for Anacor Pharmaceuticals and an investigator for GSK. Drs Secci, Zhao, and Kornyeyeva and Ms Smith are employees of Otsuka Pharmaceutical Development and Commercialization Inc. Dr Eichenfield served as a consultant and investigator for Anacor Pharmaceuticals and Otsuka Pharmaceutical. |
Vol 75 - N° 2
P. 297-305 - août 2016 Retour au numéro
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