title: Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study.
abstract: BACKGROUND
  Phosphodiesterase type 4 (PDE4) inhibition is a well-known anti-inflammatory mechanism. However, the clinical use of PDE4 inhibitors has been compromised by the occurrence of mechanism-associated adverse reactions, which often limit the maximum tolerated dose. To minimize systemic exposure, a topically active PDE4 inhibitor with low transdermal bioavailability could be clinically useful. The purpose of this study was to evaluate the efficacy of a novel topical PDE4 inhibitor, E6005, in patients with atopic dermatitis.
  
  
  METHODS
  This randomized, investigator-blinded, vehicle-controlled, multiple ascending dose study included 40 adult male patients with atopic dermatitis, who were randomly assigned to 10 days of treatment with either E6005 ointment (0.01, 0.03, 0.1 or 0.2%) or vehicle ointment.
  
  
  RESULTS
  Of 81 patients screened, 40 who had typical lesions on their posterior trunk were randomized into the study. One patient receiving 0.03% E6005 treatment discontinued because of acute gout and one receiving vehicle treatment discontinued because of progression of atopic dermatitis. The targeted lesion severity scores decreased in a concentration-dependent manner in patients treated with E6005. This drop was significant in the 0.2% E6005 ointment treatment group (mean percent change: -54.30%, p = 0.007).
  
  
  CONCLUSIONS
  E6005 ointment showed anti-inflammatory efficacy in adult patients with atopic dermatitis.
authors.affiliation: a Eisai Product Creation Systems, Eisai Co Ltd , Tokyo , Japan ;
authors.forename: Fuminori
authors.initials: F
authors.lastname: Ohba
authors.affiliation: b Sugioka Memorial Hospital Clinical Research Center , Fukuoka , Japan ;
authors.forename: Shunji
authors.initials: S
authors.lastname: Matsuki
authors.affiliation: c Imayama Shuhei Clinic and Laboratory , Fukuoka , Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Imayama
authors.affiliation: b Sugioka Memorial Hospital Clinical Research Center , Fukuoka , Japan ;
authors.forename: Kyoko
authors.initials: K
authors.lastname: Matsuguma
authors.affiliation: a Eisai Product Creation Systems, Eisai Co Ltd , Tokyo , Japan ;
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Hojo
authors.affiliation: a Eisai Product Creation Systems, Eisai Co Ltd , Tokyo , Japan ;
authors.forename: Maiko
authors.initials: M
authors.lastname: Nomoto
authors.affiliation: a Eisai Product Creation Systems, Eisai Co Ltd , Tokyo , Japan ;
authors.forename: Hideto
authors.initials: H
authors.lastname: Akama
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009824:Ointments / Q000627:therapeutic use; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage*; D010795:Phthalic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D009824:Ointments; D058988:Phosphodiesterase 4 Inhibitors; D010795:Phthalic Acids; D011799:Quinazolines; C583128:methyl 4-(((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl)amino)carbonyl)benzoate
keywords: Atopic eczema; clinical trial; phosphodiesterase 4 inhibitor; topical treatment