title: Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: Results from a randomized, vehicle-controlled exploratory trial.
abstract: This exploratory study was designed to evaluate the safety and efficacy profile of the topical phosphodiesterase 4 inhibitor E6005 in Japanese children with mild-to-moderate atopic dermatitis. The present randomized, multicenter study included 62 patients who were treated with 0.05% E6005, 0.2% E6005 or vehicle ointment twice daily for 2 weeks. Safety and pharmacokinetics were assessed with a focus on the occurrence of adverse events and the whole blood concentrations of E6005 and its metabolite. Exploratory efficacy evaluations included assessments of lesion severity and pruritus score. The 2-week application of topical E6005 was safe and well tolerated with no cutaneous adverse events. The whole blood concentration of E6005 was quantified in only one subject receiving 0.2% E6005 treatment, while its major metabolite was undetectable. The 0.2% E6005 group showed a greater decrease in the severity score than the vehicle group (-45.94% vs -32.26%), although this difference was not statistically significant. Similarly, the treatment success rate according to the investigator's global assessment of the total application sites was higher in the 0.2% E6005 group than in the vehicle group (34.4% vs 20.0%). Moreover, the 0.2% E6005 group showed a greater decrease in the pruritus score than the vehicle group (-37.5% vs -6.7%) in a predefined subpopulation. The efficacy of 0.05% E6005 treatment was comparable to that of vehicle treatment. These results suggest that topical 0.2% E6005 treatment is safe and effective in children with atopic dermatitis, although further large confirmatory clinical trials are warranted.
authors.affiliation: Kojinkai Sapporo Skin Clinic, Hokkaido, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nemoto
authors.affiliation: Department of Dermatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Japan/Asia Clinical Research, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Kitahara
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.affiliation: Global Pharmacokinetics & Bioanalysis, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Hojo
authors.affiliation: Global Pharmacokinetics & Bioanalysis, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Nomoto
authors.affiliation: Japan/Asia Clinical Research, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shima
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000982:Antipruritics / Q000008:administration & dosage / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage* / Q000097:blood; D010795:Phthalic Acids / Q000008:administration & dosage* / Q000097:blood; D011799:Quinazolines / Q000008:administration & dosage* / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000982:Antipruritics; 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: E6005; atopic dermatitis; children; phosphodiesterase 4 inhibitor; topical drug