Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis

Abstract

Objectives: The purpose of the present studies was to assess the safety, tolerability and pharmacokinetics of topical application of a novel phosphodiesterase inhibitor, E6005, in healthy volunteers and in patients with atopic dermatitis (AD). Methods: In two randomized, investigator-blind, vehicle-controlled studies, we evaluated the topical application of E6005 ointment at concentrations ranging from 0.01% to 0.2% in healthy volunteers (Study 001) and in patients with AD (Study 101). Results: Thirty-six subjects were enrolled in Study 001 and 40 in Study 101. Neither skin irritation nor photosensitization was observed with application of E6005 in Study 001. Four subjects receiving E6005 in Study 001 experienced a treatment-emergent adverse event (application site edema, increased alanine aminotransferase or erythema); three of these subjects discontinued the study. Two subjects receiving E6005 in Study 101 experienced an adverse event (gout or enterocolitis); one discontinued the study. Plasma concentrations of E6005 were below the limit of quantification (1 ng/ml) in both studies. Conclusion: E6005 ointment exhibited acceptable safety and tolerability. Topical application of E6005 ointment resulted in very low systemic exposure to E6005 in healthy volunteers and in patients with AD.

• Atopic eczema
• clinical trial
• patch test
• phosphodiesterase-4 inhibitor
• photopatch test
• topical treatment

Acknowledgements

We would like to thank the investigators and their teams at the Sekino Clinical Pharmacology Clinic and the Kyushu Clinical Pharmacology Research Clinic. Gratitude is expressed to Professor Akiyoshi Fukamizu (University of Tsukuba) for his critical reading of the article.

Declaration of interest

F.O., M.N., S.H. and H.A. are employed by Eisai Co., Ltd., which holds patents on E6005 (US7939540, EP1992622, JP4778550). Eisai Co, Ltd. manufactured the E6005 ointment, sponsored the present studies, was involved in the design and execution of the studies; in the collection, analysis and interpretation of data; and in the preparation, review and approval of the article prior to submission.