title: 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.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Further confirmatory phase-III studies are required.
  
  
  CONCLUSIONS
  OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.
authors.affiliation: Oregon Health and Science University, Portland, Oregon.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Hanifin
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Ellis
authors.affiliation: University of California, San Francisco School of Medicine, San Francisco, California.
authors.forename: Ilona J
authors.initials: IJ
authors.lastname: Frieden
authors.affiliation: University Clinics of Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Fölster-Holst
authors.affiliation: Henry Ford Health Systems, Detroit, Michigan.
authors.forename: Linda F
authors.initials: LF
authors.lastname: Stein Gold
authors.affiliation: Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey.
authors.forename: Angelo
authors.initials: A
authors.lastname: Secci
authors.affiliation: Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey.
authors.forename: Cathy
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey. Electronic address: elena.kornyeyeva@otsuka-us.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Kornyeyeva
authors.affiliation: University of California, San Diego School of Medicine and Rady Children's Hospital, San Diego, California.
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Eichenfield
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000840:Anisoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D003876:Dermatitis, Atopic / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000840:Anisoles; C119208:MM 36; D009570:Nitriles; D058988:Phosphodiesterase 4 Inhibitors
keywords: OPA-15406; atopic dermatitis; atopic eczema; phosphodiesterase type 4 inhibitor; topical agents; topical calcineurin inhibitor