Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study

Pediatric Dermatology - Tập 33 Số 4 - Trang 380-387 - 2016
Lee T. Zane1, Leon Kircik2, Robert S. Call3, Eduardo Tschen4, Zoe Diana Draelos5, Sanjay Chanda1, Merrie Van Syoc1, Adelaide A. Hebert6
1Anacor Pharmaceuticals, Palo Alto, California
2DermResearch, Louisville, Kentucky
3St. Louis University, St. Louis, Missouri
4Academic Dermatology Associates, Albuquerque, New Mexico
5Dermatology Consulting Services, High Point, North Carolina
6University of Texas Health Science Center, Houston, Texas

Tóm tắt

AbstractBackgroundPhosphodiesterase‐4 (PDE4) is a promising target in atopic dermatitis (AD) treatment. The pharmacokinetics (PK), safety, and efficacy of crisaborole topical ointment, 2% (formerly AN2728) (Anacor Pharmaceuticals, Palo Alto, CA), a boron‐based benzoxaborole PDE4 inhibitor, were evaluated in children with mild to moderate AD.MethodsThis phase 1b, open‐label, maximal‐use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg/cm2) for 28 days enrolled patients ages 2 to 17 years with extensive AD involving 25% or more or 35% or more treatable body surface area, depending on age. Primary PK and safety assessments included systemic exposure to crisaborole and its metabolites after 7 days of treatment and the incidence of treatment‐emergent adverse events (TEAEs). Secondary efficacy assessments included change from baseline in Investigator Static Global Assessment (ISGA), treatment success (ISGA score ≤1 with a two‐grade or greater improvement from baseline), and improvement in five AD signs and symptoms.ResultsOf 34 patients enrolled, 31 completed the study. Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8. Twenty‐three of 34 patients reported one or more TEAEs; 95% were mild or moderate and one patient discontinued because of a TEAE. Mean ISGA scores declined from 2.65 at baseline to 1.15 at day 29, 47.1% of patients achieved treatment success, and 64.7% of patients achieved ISGA scores of clear (0) or almost clear . Mean severity scores for AD signs and symptoms declined throughout the study.ConclusionsThis open‐label study provides evidence that crisaborole topical ointment, 2% was well tolerated, with limited systemic exposure under maximal‐use conditions in patients ages 2 years and older.

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Thông tin xuất bản

Pediatric Dermatology

Tập 33 Số 4

380-387

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