Long-term efficacy and safety of pitolisant for residual sleepiness due to Obstructive Sleep Apnea

In people with obstructive sleep apnea (OSA) excessive daytime sleepiness is a prominent symptom and can persist despite adherence to continuous positive airway pressure (CPAP), the first line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (HAROSA 1) and the other in patients refusing or not tolerating CPAP (HAROSA 2).Does the efficacy and safety of pitolisant persist when these patients take it long-term?All adults included in the HAROSA RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/day) following completion of the short-term double-blind phase, (i.e., from week 13) in an open-label cohort study. The primary efficacy outcome was the change in the Epworth Sleepiness Score (ESS) between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE), serious TEAE and special interest TEAE.Out of 512 adults included in the two RCTs, 376 completed the 1-year follow-up. The pooled mean difference in ESS from baseline to one year for the Intention to Treat sample was -8.0 [-8.3, -7.5]. The overall proportions of TEAE, TESAE and TEAESI were 35.1%, 2.0% and 11.1%, respectively, without any significant difference between patients in the initial pitolisant and placebo arms. No cardiovascular safety issues were reported.Pitolisant is effective in reducing daytime sleepiness over one year in adults with OSA, with or without CPAP treatment. Taken for one year it has a good safety profile (including cardiovascular).gov registry: HAROSA-1 NCT01071876 and HAROSA-2 NCT01072968.