Mixed Salts Oxybate Improves Daytime Performance in Individuals with Idiopathic Hypersomnia
As published by The Lancet Neurology, mixed salts (calcium, magnesium, potassium, sodium) oxybate (Xywav; Jazz Pharmaceuticals, Dublin, Ireland) phase 3 trial (NCT03533114) shows clinically meaningful improvement in idiopathic hypersomnia (IH) symptoms, such as excessive daytime sleepiness (EDS), prolonged sleep duration, and sleep inertia. The trial analyzed the change the change in the Epworth Sleepiness Scale (ESS) score and measurements that assessed patients’ perceptions of the changes in their idiopathic hypersomnia overall (PGIc).
All participants in the study received oxybates and their mean ESS score dropped from mean 16.1±3.6 points to 6.3±4.3 to 7.0±5.0. After their ESS score dropped, participants were randomly assigned to continue getting oxybates or to have it replaced with placebo. The group of participants who continued oxybates maintained ESS mean scores of 6.3±4.3 to 7.0±5.0, which is within the typical range of people without IH or other sleep disorders. The group who received placebo had their scores increase (worsen) by 5.8±3.7 to 13.3±4.1 points, indicating levels of daytime sleepiness consistent with IH.
The difference between mean scores in participants who had oxybate vs placebo was 6.5 points (95% Cl, -8.0 to -5.0; P<.0001). The participants mean baseline IHSS score was 32.1±8.0, which dropped to 15.5± to 16.9±8.1 and was maintained with oxybate treatment. Participants who switched to placebo had IHSS score increase from 15.2±7.8 to 28.5±9.0, a 12.0-point difference from oxybates (95%CI, -15.0 to -8.0; P<.0001). A score of 22 or more is considered diagnostic of IH on the IHSS score.
Clinically meaningful and statistically significant changes also occurred with oxybates vs placebo on the Clinical Global Impression of Change (CGIc), the Functional Outcomes of Sleep Questionnaire (FOSQ-10).
“The full data set from the largest global phase 3 trial in adults with idiopathic hypersomnia represents a major advance in this condition and will enable physicians to make more informed, evidence-driven treatment decisions,” said Yves Dauvilliers, MD, PhD, lead investigator of the study and director of the Sleep and Wake Disorders Centre in the Department of Neurology at the Gui de Chauliac Hospital in Montpellier, France. “The trial results demonstrate that Xywav offers significant and clinically meaningful improvements to multiple aspects of this debilitating condition that can benefit the sleep and daily lives of adults diagnosed with this unique sleep disorder.”
Treatment-emergent adverse events (TEAEs) reported by more than 10% of the participants in the trial included anxiety (11%), dizziness (12%), headache (18%), nausea (22%), and vomiting (11%). Most participants experienced TEAEs that were mild or moderate and no deaths occurred during the trial.