Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open‐Label Phase 2a Study

Pediatric Dermatology - Tập 33 Số 2 - Trang 150-159 - 2016
Wynnis L. Tom1, Merrie Van Syoc2, Sanjay Chanda2, Lee T. Zane2
1University of California San Diego and Rady Children's Hospital, San Diego, California
2Anacor Pharmaceuticals, Palo Alto, California

Tóm tắt

AbstractBackgroundPhosphodiesterase‐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).MethodsAdolescent 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.ResultsTwenty‐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%.ConclusionThese results provide preliminary evidence for the limited systemic exposure, safety, and effectiveness of crisaborole topical ointment, 2% in adolescents with mild to moderate AD.

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Tài liệu tham khảo

10.1016/j.jaad.2014.03.023

10.1056/NEJMra074081

10.1016/j.jaci.2006.03.045

10.2310/7750.2013.12119

10.1542/peds.105.4.794

10.1016/j.jaad.2005.01.010

Addendum: Update on Calcineurin Inhibitor Pediatric Literature Review. U.S. Food and Drug Administration 2011 [online].http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM255140.pdf. (accessed August 31 2015).

10.1038/sj.jid.5700622

10.1001/jamadermatol.2014.4305

10.1016/j.jaad.2015.02.1116

Dastidar SG, 2007, Therapeutic benefit of PDE4 inhibitors in inflammatory diseases, Curr Opin Investig Drugs, 8, 364

10.2174/187152807780077318

10.1016/j.febslet.2012.07.058

Higgs G, 2010, Is PDE4 too difficult a drug target?, Curr Opin Investig Drugs, 11, 495

10.1016/j.bmcl.2009.03.007

Nazarian R, 2009, AN‐2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis, Curr Opin Investig Drugs, 10, 1236

Hanifin JM, 1980, Diagnostic features of atopic dermatitis, Acta Derm Venereol Suppl (Stockh), 60, 44, 10.2340/00015555924447

Apremilast [package insert].Summit NJ:Celgene 2014.

Roflumilast [package insert].Wilmington DE:AstraZeneca Pharmaceuticals 2015.

10.1016/j.jaad.2015.03.049

10.1136/annrheumdis-2013-205056

10.1016/S0140-6736(14)62410-7

Murrell DF, 2015, Crisaborole topical ointment, 2% in adults with atopic dermatitis: a phase 2a, vehicle‐controlled, proof‐of‐concept study, J Drugs Dermatol, 14, 1108

Stein Gold LF, 2015, A phase 2, randomized, controlled, dose‐ranging study evaluating AN2728 topical ointment, 0.5% and 2% in adolescents with mild to moderate atopic dermatitis, J Drugs Dermatol, 14, 611

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Pediatric Dermatology

Tập 33 Số 2

150-159

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