Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open‐Label, Maximal‐Use Systemic Exposure Study. Issue 4 (18th May 2016)

• Record Type: Journal Article
• Authors: Zane, Lee T.; Kircik, Leon; Call, Robert; Tschen, Eduardo; Draelos, Zoe Diana; Chanda, Sanjay; Van Syoc, Merrie; Hebert, Adelaide A.
• Is Part Of: Pediatric dermatology. Volume 33:Issue 4(2016:Jul./Aug.)
• Page Start: 380
• Page End: 387
• Publication Date: 2016-05-18
• Subjects: Pediatric dermatology -- Periodicals; Children -- Diseases -- Periodicals; 618.925
• DOI: 10.1111/pde.12872
• Languages: English
• ISSNs: 0736-8046

Abstract

Abstract: Background: Phosphodiesterase‐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. Methods: This phase 1b, open‐label, maximal‐use study of crisaborole topical ointment, 2% applied twice daily (dose 3 mg/cm 2 ) 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. Results: Of 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 clear1 . Mean severity scores for AD signs and symptoms declined throughout the study. Conclusions: This 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.