title: Crisaborole Topical Ointment, 2% in Patients Ages 2 to 17 Years with Atopic Dermatitis: A Phase 1b, Open-Label, Maximal-Use Systemic Exposure Study.
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 clear . 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.
authors.affiliation: Anacor Pharmaceuticals, Palo Alto, California.
authors.forename: Lee T
authors.initials: LT
authors.lastname: Zane
authors.affiliation: DermResearch, Louisville, Kentucky.
authors.forename: Leon
authors.initials: L
authors.lastname: Kircik
authors.affiliation: St. Louis University, St Louis, Missouri.
authors.forename: Robert
authors.initials: R
authors.lastname: Call
authors.affiliation: Academic Dermatology Associates, Albuquerque, New Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tschen
authors.affiliation: Dermatology Consulting Services, High Point, North Carolina.
authors.forename: Zoe Diana
authors.initials: ZD
authors.lastname: Draelos
authors.affiliation: Anacor Pharmaceuticals, Palo Alto, California.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chanda
authors.affiliation: Anacor Pharmaceuticals, Palo Alto, California.
authors.forename: Merrie
authors.initials: M
authors.lastname: Van Syoc
authors.affiliation: University of Texas Health Science Center, Houston, Texas.
authors.forename: Adelaide A
authors.initials: AA
authors.lastname: Hebert
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D001896:Boron Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D009824:Ointments / Q000627:therapeutic use; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D009824:Ointments; D058988:Phosphodiesterase 4 Inhibitors; C543085:crisaborole