Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study

Abstract

Introduction: 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). Conclusion: E6005 ointment showed anti-inflammatory efficacy in adult patients with atopic dermatitis.

Keywords:

• Atopic eczema
• clinical trial
• phosphodiesterase 4 inhibitor
• topical treatment

Acknowledgements

We gratefully acknowledge the contributions of patients and staff at Kyushu Clinical Pharmacology Research Clinic. We also thank Toshifumi Saito for clinical operation, Chizuko Matsumura for support in data management, and Mikiko Kawakatsu for editorial support in writing the clinical study report. Gratitude is expressed to Prof. Akiyoshi Fukamizu (University of Tsukuba) for his critical reading of the manuscript.

Disclosure statement

Fuminori Ohba, Maiko Nomoto, Seiichiro Hojo, and Hideto Akama are employed by Eisai Co. Ltd., which holds patents on E6005 (US7939540, EP1992622, JP4778550). Eisai Co, Ltd. manufactured the E6005 ointment and sponsored the present studies, and was involved in the design and execution of the studies; data collection, analysis and interpretation; and preparation, review and approval of the manuscript before submission. Shunji Matsuki, Kyoko Matsuguma and Shuhei Imayama disclose no conflicts of interest.