BACKGROUND
Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. We aimed to evaluate the efficacy and safety of pitolisant, a selective histamine H3-receptor antagonist with wake-promoting effects, for treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment.
METHODS
In an international multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mg/day over 12 weeks. Primary endpoint was the change in the Epworth Sleepiness score. Key secondary endpoints were maintenance of wakefulness assessed by the Oxford Sleep Resistance Test, safety, clinical global impressions of severity, patient's global opinion, EQ-5D quality-of-life, and Pichot Fatigue questionnaire scores.
RESULTS
268 obstructive sleep apnea patients (75% male; mean age: 52 years, Apnea-hypopnea index: 49/hour, baseline sleepiness score: 15.7) were randomized (200 pitolisant; 68 placebo) and analyzed in intention to treat. The Epworth Sleepiness score was more reduced with pitolisant than with placebo -2.8 (95% CI: [-4.0;-1.5]) (p<.001). Wake maintenance tests were not improved. The Pichot fatigue score was reduced with pitolisant. The overall impact of pitolisant was confirmed by both physicians' and patients' questionnaires. Adverse event incidence, mainly headache, insomnia, nausea, and vertigo, was similar in the pitolisant and placebo groups (29.5% and 25.4%, respectively), with no cardiovascular or other significant safety concerns.
CONCLUSIONS
Pitolisant significantly reduced self-reported daytime sleepiness, fatigue and improved patient-reported outcomes and physician disease severity assessment in sleepy patients with obstructive sleep apnea refusing or non-adherent to continuous positive airway pressure. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01072968.