487 Effect of Lower-Sodium Oxybate on Sleep Inertia in Idiopathic Hypersomnia in a Double-Blind, Randomized Withdrawal Study. (3rd May 2021)

• Record Type: Journal Article
• Authors: Bogan, Richard; Dauvilliers, Yves; Thorpy, Michael; Chandler, Patricia; Chen, Abby; Chen, Dan; Arnulf, Isabelle
• Is Part Of: Sleep. Volume 44(2021)Supplement 2
• Page Start: A192
• Page End: A192
• Publication Date: 2021-05-03
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsab072.486
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder characterized by excessive daytime sleepiness. A common feature is sleep inertia, which is prolonged difficulty waking up accompanied by confusion, disorientation, poor motor coordination, and repeated returns to sleep. Sleep inertia is burdensome to patients, resulting in missed work or school, and patients may be dependent on others to wake them. No treatment is currently approved for IH. The efficacy and safety of lower-sodium oxybate (LXB; Xywav™), a novel oxybate treatment with 92% less sodium than sodium oxybate (Xyrem®), was evaluated in a phase 3 study (NCT03533114) in adults with IH. We focus here on the drug effect on sleep inertia. Methods: Eligible participants aged 18–75 years with IH began LXB treatment with an open-label treatment titration and optimization period (OLTTOP; 10–14 weeks), followed by a 2-week, open-label, stable-dose period (SDP). Participants were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). The primary efficacy endpoint was change in Epworth Sleepiness Scale score. The visual analog scale for sleep inertia (VAS-SI) was included as an exploratory endpoint. The VAS-SI, administered daily during the last 2 weeks of screening before baseline, SDP, and DBRWP, is a self-reported retrospective measure of difficulty awakening each morning using a 100-mm line with anchors 0 (very easy) and 100 (very difficult). Results: The safety population included 154 participants (mean±SD age, 40±14 years; 68% female); modified intent-to-treat population, n=115. VAS-SI scores gradually decreased from week 2 of screening (mean±SD, 56.6±25.1) to week 2 of SDP (29.0±20.8). During week 2 of DBRWP, VAS-SI scores worsened in participants randomized to placebo (n=59) compared with maintenance of improvement in participants continuing LXB treatment (n=56); LS mean difference (95% CI) in change from SDP, −22.2 (−29.7, −14.8); P<0.0001 (nominal). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%). Conclusion: Sleep inertia improved with LXB treatment and significant differences were seen between placebo and LXB after DBRWP. The overall safety profile in participants with IH is consistent with that of LXB in narcolepsy. Support (if any): Jazz Pharmaceuticals, Inc