Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study.
adolescent
apremilast
children
pediatric
pharmacokinetics
plaque psoriasis
safety
Journal
Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
17
01
2019
revised:
26
07
2019
accepted:
03
08
2019
pubmed:
14
8
2019
medline:
21
8
2020
entrez:
14
8
2019
Statut:
ppublish
Résumé
No oral systemic treatments are approved for pediatric patients with psoriasis. To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis. This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index. A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children. No children weighing less than 20 kg were enrolled. This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.
Sections du résumé
BACKGROUND
BACKGROUND
No oral systemic treatments are approved for pediatric patients with psoriasis.
OBJECTIVE
OBJECTIVE
To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis.
METHODS
METHODS
This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index.
RESULTS
RESULTS
A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children.
LIMITATIONS
CONCLUSIONS
No children weighing less than 20 kg were enrolled.
CONCLUSIONS
CONCLUSIONS
This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.
Identifiants
pubmed: 31408686
pii: S0190-9622(19)32566-6
doi: 10.1016/j.jaad.2019.08.019
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Phosphodiesterase 4 Inhibitors
0
Thalidomide
4Z8R6ORS6L
apremilast
UP7QBP99PN
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
389-397Informations de copyright
Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.