Pharmacokinetics of pitolisant in children and adolescents with narcolepsy.

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.