TY - JOUR
T1 - Pharmacokinetics of pitolisant in children and adolescents with narcolepsy
AU - Lecendreux, Michel
AU - Plazzi, Giuseppe
AU - Franco, Patricia
AU - Jacqz-Aigrain, Evelyne
AU - Robert, Philippe
AU - Duvauchelle, Thierry
AU - Schwartz, Jean Charles
N1 - Funding Information:
This study was funded by Bioprojet Pharma, Paris, France . Technical editorial and medical writing assistance was provided under the direction of the authors by Kulvinder Singh, PharmD, and Nancy Holland, PhD, of Synchrony Medical Communications, LLC, West Chester, PA, USA, and funded by Harmony Biosciences, LLC, Plymouth Meeting, PA, USA .
Funding Information:
M.L. reports serving as a consultant and participating in advisory boards for NLS Pharma, Jazz Pharmaceuticals, UCB Pharma, and Bioprojet; and receiving grant support from Shire. G.P. reports participating in advisory boards for UCB, Jazz Pharmaceuticals, and Bioprojet. P.F. reports serving on the speakers’ bureau and participating in advisory boards for UCB and Procter & Gamble; and serving as an investigator for clinical studies sponsored by Bioprojet. E.J.A. reports no conflicts of interest. P.R. is an employee of Bioprojet Biotech. T.D. is an employee of Bioprojet Pharma. J.C.S. is a co-founder of Bioprojet Pharma. The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: https://doi.org/10.1016/j.sleep.2019.10.024 .
Publisher Copyright:
© 2019
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - Objective: To evaluate the pharmacokinetic profile and tolerability of pitolisant, a selective histamine 3 (H3)−receptor antagonist/inverse agonist, in children and adolescents with narcolepsy. Methods: This multicenter, open-label, single-dose study of pitolisant 17.8 mg enrolled patients aged 6 through 17 years with a diagnosis of narcolepsy. Blood samples were collected at prespecified time points for analysis of pharmacokinetic parameters, including maximum serum concentration (Cmax) and area under the serum concentration–time curve from time 0–10 h (AUC0–10h). Pharmacokinetic parameters were compared across three prespecified age groups: younger pediatric patients (aged 6 to <12 years), older pediatric patients (aged 12 to <18 years), and a historical comparison group of young adults (aged 18 to <45 years). Results: Of the 25 enrolled patients, 24 were included in the pharmacokinetic analysis. Pitolisant Cmax and AUC0–10h were greater (by 52% and 73%, respectively) in the younger (n = 12) versus older (n = 12) pediatric subgroup. These parameters were lower in the young adult group (n = 13) by 51% and 48%, respectively, compared with the older pediatric patients, and by 68% and 70%, respectively, compared with the younger pediatric patients. There were six treatment-emergent adverse events: headache (three), dizziness (one), diarrhea (one), and vomiting (one). Conclusions: After single-dose administration, the exposure parameters of pitolisant were significantly greater in the younger compared with older pediatric patients with narcolepsy. Pitolisant doses up to 17.8 mg/d (in children with body weight <40 kg) or 35.6 mg/d are appropriate for further evaluation in pediatric patients. Trial registration: EudraCT Number: 2013-001505-93.
AB - Objective: To evaluate the pharmacokinetic profile and tolerability of pitolisant, a selective histamine 3 (H3)−receptor antagonist/inverse agonist, in children and adolescents with narcolepsy. Methods: This multicenter, open-label, single-dose study of pitolisant 17.8 mg enrolled patients aged 6 through 17 years with a diagnosis of narcolepsy. Blood samples were collected at prespecified time points for analysis of pharmacokinetic parameters, including maximum serum concentration (Cmax) and area under the serum concentration–time curve from time 0–10 h (AUC0–10h). Pharmacokinetic parameters were compared across three prespecified age groups: younger pediatric patients (aged 6 to <12 years), older pediatric patients (aged 12 to <18 years), and a historical comparison group of young adults (aged 18 to <45 years). Results: Of the 25 enrolled patients, 24 were included in the pharmacokinetic analysis. Pitolisant Cmax and AUC0–10h were greater (by 52% and 73%, respectively) in the younger (n = 12) versus older (n = 12) pediatric subgroup. These parameters were lower in the young adult group (n = 13) by 51% and 48%, respectively, compared with the older pediatric patients, and by 68% and 70%, respectively, compared with the younger pediatric patients. There were six treatment-emergent adverse events: headache (three), dizziness (one), diarrhea (one), and vomiting (one). Conclusions: After single-dose administration, the exposure parameters of pitolisant were significantly greater in the younger compared with older pediatric patients with narcolepsy. Pitolisant doses up to 17.8 mg/d (in children with body weight <40 kg) or 35.6 mg/d are appropriate for further evaluation in pediatric patients. Trial registration: EudraCT Number: 2013-001505-93.
KW - Adolescent
KW - Child
KW - Narcolepsy
KW - Pediatric
KW - Pharmacokinetics
KW - Pitolisant
UR - http://www.scopus.com/inward/record.url?scp=85078007587&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078007587&partnerID=8YFLogxK
U2 - 10.1016/j.sleep.2019.10.024
DO - 10.1016/j.sleep.2019.10.024
M3 - Article
C2 - 31978866
AN - SCOPUS:85078007587
VL - 66
SP - 220
EP - 226
JO - Sleep Medicine
JF - Sleep Medicine
SN - 1389-9457
ER -