Pitolisant safe, improved symptoms of narcolepsy in children

Key takeaways:

• Pitolisant 5 mg to 40 mg a day improved symptoms of narcolepsy in children aged 6 to 17 years.
• Safety profile similar to that seen in adults, with generally mild adverse events.

Treatment with pitolisant demonstrated significant efficacy in reducing excessive daytime sleepiness and cataplexy in children aged 6 years and older, according to research presented in The Lancet Neurology.

“Narcolepsy is a rare neurological disorder commonly starting in childhood and adolescence, with a peak of onset at the age of approximately 15 years,” Yves Dauvilliers, MD, professor of neurology and physiology at the University of Montpellier in France, and colleagues wrote. “Narcolepsy is currently treated with lifestyle advice and symptomatic pharmacological treatment aiming to alleviate symptoms and improve daily functioning and the disease burden.”

Pitolisant, a selective histamine H3 receptor inverse agonist, has demonstrated good safety and efficacy in adults with narcolepsy, prompting researchers to assess its effects in children and adolescents.

Dauvilliers and colleagues conducted a double-blind, randomized, placebo-controlled study of patients aged 6 to 17 years with narcolepsy, with or without cataplexy, at 11 sleep centers in Italy, France, Netherlands, Russia, Finland. Of 115 individuals screened for eligibility, 110 participants (mean age, 12.9 years; 55% boys; 82% with cataplexy) with a score of at least 15 on the Pediatric Daytime Sleepiness Scale and who did not receive psychostimulants at least 14 days before enrollment were assigned on a 2:1 basis to receive pitolisant or placebo.

After a 4-week screening period including a 2-week baseline period, participants were given pitolisant or placebo for 8 weeks in escalating doses, up to 40 mg per day for patients who weighed more than 40 kg. All patients received placebo for a 1-week washout.

The primary outcome was change in the 11-item Ullanlinna Narcolepsy Scale (UNS) total score from baseline to the end of the double-blind period, with a decrease indicating reductions in excessive daytime sleepiness and cataplexy.

From the initial treatment cohort, 107 participants (pitolisant, n = 70; placebo, n = 37) completed the 8-week, double-blind period. Researchers reported the adjusted difference in UNS total score from baseline to the end of treatment was –6.3 for those given pitolisant and –2.6 for placebo recipients (least squares mean difference = –3.7; 95% CI –6.4 to –1).

Treatment-emergent adverse events were reported in 31% of pitolisant recipients and 34% in the placebo group, with no deaths, serious adverse events or pitolisant discontinuations reported as a result of treatment. The most frequently reported adverse events in either group were headaches and insomnia.

“The safety profile of pitolisant was consistent with that observed in adults and adverse events were generally mild, suggesting good benefit-risk profile,” Dauvilliers and colleagues wrote.