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

Jon Hanifin, Charles N. Ellis, Ilona J. Frieden, Regina Fölster-Holst, Linda F. Stein Gold, Angelo Secci, Angela J. Smith, Cathy Zhao, Elena Kornyeyeva, Lawrence F. Eichenfield

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51 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalJournal of the American Academy of Dermatology
DOIs
StateAccepted/In press - 2016

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Keywords

  • Atopic dermatitis
  • Atopic eczema
  • OPA-15406
  • Phosphodiesterase type 4 inhibitor
  • Topical agents
  • Topical calcineurin inhibitor

ASJC Scopus subject areas

  • Dermatology

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