OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study

• Published in: Journal of the American Academy of Dermatology 2016-08, Vol.75 (2), p.297-305
• Main Authors: Hanifin, Jon M., MD, Ellis, Charles N., MD, Frieden, Ilona J., MD, Fölster-Holst, Regina, MD, Stein Gold, Linda F., MD, Secci, Angelo, MD, Smith, Angela J., PA, Zhao, Cathy, PhD, Kornyeyeva, Elena, MD, PhD, Eichenfield, Lawrence F., MD
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adolescent; Adult; Anisoles - adverse effects; Anisoles - blood; Anisoles - therapeutic use; atopic dermatitis; atopic eczema; Child; Dermatitis, Atopic - complications; Dermatitis, Atopic - drug therapy; Dermatology; Double-Blind Method; Female; Humans; Male; Middle Aged; Nitriles - adverse effects; Nitriles - blood; Nitriles - therapeutic use; OPA-15406; Phosphodiesterase 4 Inhibitors - adverse effects; Phosphodiesterase 4 Inhibitors - blood; Phosphodiesterase 4 Inhibitors - therapeutic use; phosphodiesterase type 4 inhibitor; Pruritus - drug therapy; Pruritus - etiology; Severity of Illness Index; topical agents; topical calcineurin inhibitor; Young Adult
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2016.04.001

Background Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. Objectives We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. Methods This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks. Results The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group ( P  = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P  = .0005), even larger in week 2 (39.0% vs 3.0%; P  = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P  = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. Limitations Further confirmatory phase-III studies are required. Conclusion OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.