Validating Pitolisant in Pediatric Patients With Narcolepsy

Pitolisant is a selective histamine H3-receptor inverse agonist that was approved for the treatment of adult patients with narcolepsy with or without cataplexy. In an article published in The Lancet Neurology, researchers led by Yves Dauvilliers, MD, evaluated pitolisant in a cohort of pediatric patients with narcolepsy with or without cataplexy.

Based on changes in Ullanlinna Narcolepsy Scale (UNS) scores, Dr. Dauvilliers and colleagues concluded pitolisant therapy improved symptoms compared with placebo in their patients. Authors noted that the UNS tool was not validated for children with narcolepsy when they began the study. A decrease in UNS total score indicated a decrease in excessive daytime sleepiness and cataplexy.

The double-blind, multicenter, phase 3, randomized, controlled trial enrolled patients aged 6 to 17 years with narcolepsy. All participants had a Pediatric Daytime Sleepiness Scale score of at least 15 and had not received psychostimulants for at least 2 weeks prior to enrollment. Additionally, patients on an anticataleptic had to be on a stable dose for at least 1 month.

Pitolisant Also Valuable for Children With Narcolepsy

After a 4-week screening period with a 2-week baseline period, the cohort was randomized 2:1 to pitolisant or placebo. Treatment consisted of 4 weeks of individualized up-titration of pitolisant or placebo from 5 mg to a maximum of 40 mg daily. Treatment was continued at a stable dose for 4 weeks, followed by a 1-week placebo period.

The primary end point of the study was change in UNS total score from baseline to the end of the double-blind period in all patients who received at least 1 dose of treatment and had at least 1 baseline UNS score.

A total of 110 patients (55% male; mean age, 12.9±3.0 years), of whom 90 (82%) had cataplexy, were randomized between pitolisant (n=72) or placebo (n=38). Of these, 70 patients in the pitolisant group and 37 in the placebo group completed the double-blind period.

Researchers calculated the mean adjusted difference from baseline in UNS total score was −6.3 (standard error [SE], 1.1) in the pitolisant group and −2.6 (SE, 1.4) in the placebo group after the double-blind period (least squares mean difference, −3.7; 95% CI, −6.4 to −1.0; P=.007).

Investigators reported treatment-emergent adverse events in 22 (31%) of 72 patients in the pitolisant group and 13 (34%) of 38 patients in the placebo group, the most common of which were headache (pitolisant, 14 [19%]; placebo, 3 [8%]) and insomnia (pitolisant, 5 [7%]; placebo, 1 [3%]).

Overall, Dr. Dauvilliers and colleagues concluded that pitolisant improved narcolepsy symptoms in children with narcolepsy and had a safety profile similar to that in adult patients. The article noted an open-label follow-up is ongoing, but “further studies are needed to confirm long-term safety.”

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