PMID- 26777394
OWN - NLM
STAT- MEDLINE
DCOM- 20170112
LR  - 20190827
IS  - 1525-1470 (Electronic)
IS  - 0736-8046 (Linking)
VI  - 33
IP  - 2
DP  - 2016 Mar-Apr
TI  - Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical 
      Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study.
PG  - 150-9
LID - 10.1111/pde.12780 [doi]
AB  - BACKGROUND: Phosphodiesterase-4 (PDE4) is an emerging target in treating 
      inflammatory skin diseases. Crisaborole topical ointment, 2% is a novel, 
      boron-based, topical PDE4 inhibitor under investigation for treatment of mild to 
      moderate atopic dermatitis (AD). METHODS: Adolescent patients aged 12 to 17 years 
      with treatable AD lesions involving >/= 10% to </= 35% body surface area (BSA) were 
      enrolled into a phase 2a, open-label study comprising pharmacokinetic (PK), 
      safety, tolerability, and efficacy assessments. Crisaborole topical ointment, 2% 
      was applied twice daily to affected areas for 28 days, with dosage based on 
      baseline treatable BSA. PK blood samples were collected on days 1, 2, 4, 6, 8, 
      and 9. Safety assessments included adverse events (AEs), laboratory parameters, 
      and vital signs. Efficacy assessments included the Investigator's Static Global 
      Assessment (ISGA) score and severity of AD signs and symptoms. RESULTS: 
      Twenty-three patients were enrolled; 22 completed the study (1 patient 
      discontinued due to an AE [application site dermatitis]). PK analysis 
      demonstrated limited exposure to crisaborole topical ointment, 2% after 8 days of 
      dosing. Ten patients reported a total of 19 AEs, most commonly application site 
      pain and nasopharyngitis (3 patients each). There were no clinically meaningful 
      changes in laboratory or vital sign parameters. Efficacy was demonstrated by 
      reductions in mean ISGA and AD sign and symptom severity scores. At day 29, eight 
      patients (35%) had achieved an ISGA score </= 1 with >/= 2-grade improvement. Mean 
      treatable BSA declined from 17.6% to 8.2%. CONCLUSION: These results provide 
      preliminary evidence for the limited systemic exposure, safety, and effectiveness 
      of crisaborole topical ointment, 2% in adolescents with mild to moderate AD.
CI  - (c) 2016 Wiley Periodicals, Inc.
FAU - Tom, Wynnis L
AU  - Tom WL
AD  - University of California, San Diego and Rady Children's Hospital, San Diego, 
      California.
FAU - Van Syoc, Merrie
AU  - Van Syoc M
AD  - Anacor Pharmaceuticals, Palo Alto, California.
FAU - Chanda, Sanjay
AU  - Chanda S
AD  - Anacor Pharmaceuticals, Palo Alto, California.
FAU - Zane, Lee T
AU  - Zane LT
AD  - Anacor Pharmaceuticals, Palo Alto, California.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160118
PL  - United States
TA  - Pediatr Dermatol
JT  - Pediatric dermatology
JID - 8406799
RN  - 0 (Boron Compounds)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Ointments)
RN  - 0 (Phosphodiesterase 4 Inhibitors)
RN  - Q2R47HGR7P (crisaborole)
SB  - IM
MH  - Administration, Topical
MH  - Adolescent
MH  - Boron Compounds/*administration & dosage/pharmacokinetics/toxicity
MH  - Bridged Bicyclo Compounds, Heterocyclic/*administration & 
      dosage/pharmacokinetics/toxicity
MH  - Child
MH  - Dermatitis, Atopic/*drug therapy
MH  - Drug Tolerance
MH  - Female
MH  - Humans
MH  - Male
MH  - Ointments
MH  - Phosphodiesterase 4 Inhibitors/*administration & dosage
EDAT- 2016/01/19 06:00
MHDA- 2017/01/14 06:00
CRDT- 2016/01/19 06:00
PHST- 2016/01/19 06:00 [entrez]
PHST- 2016/01/19 06:00 [pubmed]
PHST- 2017/01/14 06:00 [medline]
AID - 10.1111/pde.12780 [doi]
PST - ppublish
SO  - Pediatr Dermatol. 2016 Mar-Apr;33(2):150-9. doi: 10.1111/pde.12780. Epub 2016 Jan 
      18.