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

  • J Am Acad Dermatol. 2016 Aug;75(2):297-305. doi: 10.1016/j.jaad.2016.04.001.
Jon M Hanifin  1 ,  Charles N Ellis  2 ,  Ilona J Frieden  3 ,  Regina Fölster-Holst  4 ,  Linda F Stein Gold  5 ,  Angelo Secci  6 ,  Angela J Smith  6 ,  Cathy Zhao  6 ,  Elena Kornyeyeva  7 ,  Lawrence F Eichenfield  8
Affiliations
  • 1. Oregon Health and Science University, Portland, Oregon.
  • 2. Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan.
  • 3. University of California, San Francisco School of Medicine, San Francisco, California.
  • 4. University Clinics of Schleswig-Holstein, Campus Kiel, Germany.
  • 5. Henry Ford Health Systems, Detroit, Michigan.
  • 6. Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey.
  • 7. Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey. Electronic address: [email protected].
  • 8. University of California, San Diego School of Medicine and Rady Children's Hospital, San Diego, California.
PMID: 27189825 DOI: 10.1016/j.jaad.2016.04.001
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.

Keywords
OPA-15406; atopic dermatitis; atopic eczema; phosphodiesterase type 4 inhibitor; topical agents; topical calcineurin inhibitor.
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