In patients with obstructive sleep apnea (OSA) who refuse or are nonadherent to continuous positive airway pressure (CPAP) therapy, treatment with pitolisant may reduce self-reported excessive daytime sleepiness, according to study results published in the American Journal of Respiratory and Critical Care Medicine.
Researchers conducted a phase 3, prospective, double-blind, randomized, placebo-controlled, parallel-design clinical trial (ClinicalTrials.gov Identifier: NCT01072968) in 28 hospital sleep clinics in 10 European countries between October 6, 2011, and May 7, 2014.
The investigators sought to assess the efficacy and safety of the selective histamine
H3-receptor antagonist pitolisant during a 12-week period for the treatment of daytime sleepiness in patients with moderate to severe OSA (defined as apnea-hypopnea index ≥15/h with an Epworth Sleepiness Scale [ESS] score of ≥12) without significant cardiovascular disease. All of the patients either refused or were not adherent to CPAP therapy.
The primary study end point was change in ESS score. Secondary end points included the following: maintenance of wakefulness as evaluated by the Oxford Sleep Resistance Test, safety, clinical global impressions of disease severity, patient’s global opinion, EuroQoL (EQ-5D) quality-of-life questionnaire, and Pichot Fatigue scale score.
A total of 268 patients with OSA were randomly assigned in a 3:1 ratio to receive pitolisant, titrated up to 20 mg/d (n=201) or placebo (n=67) over 12 weeks. Overall, 75.4% of the patients were men and the mean patient age was 52 years.
Results of the study demonstrated that ESS scores were significantly reduced among patients in the pitolisant group compared with placebo (-2.8 reduction in ESS with pitolisant; 95% CI, -4.0 to -1.5; P <.001). Wake maintenance tests, however, were not improved with pitolisant. In addition, treatment with pitolisant was associated with reductions in Pichot Fatigue scores, with a significant mean change between groups (-3.6±5.6 vs -1.0±6.3; P =.005). Both patients’ and physicians’ questionnaires confirmed the overall effect of treatment with pitolisant.
The incidence of adverse events was similar in both the pitolisant and placebo groups (29.5% vs 25.4.%, respectively), consisting mainly of headache, insomnia, nausea, and vertigo. No cardiovascular or other significant safety concerns were reported.
According to the investigators, a limitation of the study was its 12-week duration; however, long-term efficacy and safety are being evaluated in an extension study.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Dauvilliers Y, Verbraecken J, Partinen M, et al; on behalf of the HAROSA II study group. Pitolisant for daytime sleepiness in obstructive sleep apnea patients refusing CPAP: a randomized trial [published online January 9, 2020]. Am J Respir Crit Care Med. doi:10.1164/rccm.201907-1284OC