Safety and Plasma Concentrations of a Cyclin-dependent Kinase 9 (CDK9) Inhibitor, FIT039, Administered by a Single Adhesive Skin Patch Applied on Normal Skin and Cutaneous Warts

• Published in: Clinical drug investigation Vol. 39; no. 1; pp. 55 - 61
• Main Authors: Sumi, Eriko, Nomura, Takashi, Asada, Ryuta, Uozumi, Ryuji, Tada, Harue, Amino, Yoko, Sawada, Teruo, Yonezawa, Atsushi, Hagiwara, Masatoshi, Kabashima, Kenji
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2019; Springer Nature B.V
• Subjects: Adhesives; Administration, Cutaneous; Adult; Aged; Clinical trials; Cryotherapy; Cryotherapy - methods; Cyclin-Dependent Kinase 9 - antagonists & inhibitors; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; Drug dosages; Female; Hepatitis; Human papillomavirus; Humans; Infections; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Original; Original Research Article; Papillomavirus Infections - drug therapy; Pharmacology/Toxicology; Pharmacotherapy; Pyridines - therapeutic use; Transdermal Patch; Viruses; Warts; Warts - drug therapy; Young Adult
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-018-0712-7

Background Cutaneous warts are caused by human papilloma virus (HPV) infection. FIT039, a specific inhibitor of CDK9, suppresses the proliferation of DNA viruses in vitro. Purpose We evaluated the safety, plasma concentrations, and efficacy of FIT039 delivered by single application of an adhesive skin patch on normal back skin and cutaneous warts. Patients and Methods In this placebo-controlled, dose-escalation, open-label, two-cohort phase I/II clinical trial, after a single administration of a 1% FIT039 patch, 3% FIT039 patch, or placebo on back skin, patients with cutaneous warts were treated with cryotherapy followed by a 1% FIT039 patch for 24 h in the first cohort. In the second cohort, cutaneous warts were treated with cryotherapy followed by a 3% FIT039 patch for 24 h. Adverse events and adverse drug reactions, the concentrations of FIT039, and surface area of cutaneous warts were evaluated. Results Neither irritant reactions nor symptoms related to FIT039 occurred when the FIT039 patches were applied to patients’ backs or on warts in ten patients. The concentrations of FIT039 were under 0.1 ng/ml at every time point. The median wart surface area at 1 week after application of the 1% FIT039 patch was similar to baseline, while that of the 3% FIT039 patch was smaller than baseline. Conclusion The FIT039 patch showed no topical or systemic adverse reactions when applied on normal skin or cutaneous warts. The safety and good adherence of the FIT039 patch are encouraging and support further studies to evaluate the efficacy of FIT039 in patients with cutaneous warts.