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Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study.
Pediatr Dermatol. 2016 Mar-Apr; 33(2):150-9.PD

Abstract

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.

Authors+Show Affiliations

University of California, San Diego and Rady Children's Hospital, San Diego, California.Anacor Pharmaceuticals, Palo Alto, California.Anacor Pharmaceuticals, Palo Alto, California.Anacor Pharmaceuticals, Palo Alto, California.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26777394

Citation

Tom, Wynnis L., et al. "Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents With Atopic Dermatitis: an Open-Label Phase 2a Study." Pediatric Dermatology, vol. 33, no. 2, 2016, pp. 150-9.
Tom WL, Van Syoc M, Chanda S, et al. Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study. Pediatr Dermatol. 2016;33(2):150-9.
Tom, W. L., Van Syoc, M., Chanda, S., & Zane, L. T. (2016). Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study. Pediatric Dermatology, 33(2), 150-9. https://doi.org/10.1111/pde.12780
Tom WL, et al. Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents With Atopic Dermatitis: an Open-Label Phase 2a Study. Pediatr Dermatol. 2016 Mar-Apr;33(2):150-9. PubMed PMID: 26777394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic Profile, Safety, and Tolerability of Crisaborole Topical Ointment, 2% in Adolescents with Atopic Dermatitis: An Open-Label Phase 2a Study. AU - Tom,Wynnis L, AU - Van Syoc,Merrie, AU - Chanda,Sanjay, AU - Zane,Lee T, Y1 - 2016/01/18/ PY - 2016/1/19/entrez PY - 2016/1/19/pubmed PY - 2017/1/14/medline SP - 150 EP - 9 JF - Pediatric dermatology JO - Pediatr Dermatol VL - 33 IS - 2 N2 - 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. SN - 1525-1470 UR - https://www.unboundmedicine.com/medline/citation/26777394/Pharmacokinetic_Profile_Safety_and_Tolerability_of_Crisaborole_Topical_Ointment_2_in_Adolescents_with_Atopic_Dermatitis:_An_Open_Label_Phase_2a_Study_ DB - PRIME DP - Unbound Medicine ER -