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.
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