PURPOSE: To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia. PATIENTS AND METHODS: Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18-75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10-14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). RESULTS: The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1-4, n = 87 [56.5%]; weeks 13-16, n = 39 [31.7%]). CONCLUSION: During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.

Albert Einstein College of Medicine Bronx NY USA

Cleveland Clinic Sleep Disorders Center Department of Neurology Lerner College of Medicine Cleveland OH USA

Department of Neurology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Formerly Jazz Pharmaceuticals Palo Alto CA USA

Janet Weis Children's Hospital Geisinger Danville PA USA

Jazz Pharmaceuticals Palo Alto CA USA

Jazz Pharmaceuticals Philadelphia PA USA

Sleep and Wake Disorders Centre Department of Neurology Gui de Chauliac Hospital Montpellier France

Sleep Disorder Unit Pitié Salpêtrière Hospital and Sorbonne University Paris France

Stanford University Center for Sleep Sciences and Medicine Palo Alto CA USA

University of Montpellier INSERM Institute Neuroscience Montpellier Montpellier France

University of South Carolina School of Medicine Columbia SC USA

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Billiard M, Sonka K. Idiopathic hypersomnia. PubMed DOI

Trotti LM. Idiopathic hypersomnia. PubMed DOI PMC

American Academy of Sleep Medicine. Idiopathic hypersomnia. In:

Vernet C, Leu-Semenescu S, Buzare MA, Arnulf I. Subjective symptoms in idiopathic hypersomnia: beyond excessive sleepiness. PubMed DOI

Arnulf I, Leu-Semenescu S, Dodet P. Precision medicine for idiopathic hypersomnia. PubMed DOI

Evangelista E, Rassu AL, Barateau L, et al. Characteristics associated with hypersomnia and excessive daytime sleepiness identified by extended polysomnography recording. PubMed DOI

Ozaki A, Inoue Y, Nakajima T, et al. Health-related quality of life among drug-naive patients with narcolepsy with cataplexy, narcolepsy without cataplexy, and idiopathic hypersomnia without long sleep time. PubMed DOI PMC

Srivastava B, Morris S, Banderas B, Lowe C, Dauvilliers Y. Patient-reported symptoms and health-related quality of life impacts of idiopathic hypersomnia [abstract]. Presented at: Annual Meeting of the American Neurological Association; October 17-19, 2021.

Pizza F, Jaussent I, Lopez R, et al. Car crashes and central disorders of hypersomnolence: a French study. PubMed DOI PMC

Dauvilliers Y, Paquereau J, Bastuji H, Drouot X, Weil JS, Viot-Blanc V. Psychological health in central hypersomnias: the French Harmony study. PubMed DOI

Bogan RK, Thorpy MJ, Dauvilliers Y, et al. Efficacy and safety of calcium, magnesium, potassium, and sodium oxybates (lower-sodium oxybate [LXB]; JZP-258) in a placebo-controlled, double-blind, randomized withdrawal study in adults with narcolepsy with cataplexy. PubMed DOI PMC

Xywav

US Food and Drug Administration. Clinical superiority findings; 2021. Available from: https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/clinical-superiority-findings. Accessed July 9, 2021.

Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study. PubMed DOI

Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Correlation of the Idiopathic Hypersomnia Severity Scale (IHSS) score with other measures of sleep parameters in a phase 3 trial [poster 500]. Presented at: Annual Meeting of the Associated Professional Sleep Societies; June 10-13, 2021.

Rassu AL, Evangelista E, Barateau L, et al. Idiopathic Hypersomnia Severity Scale to better quantify symptoms severity and their consequences in idiopathic hypersomnia. PubMed DOI PMC

American Academy of Sleep Medicine. Idiopathic hypersomnia with long sleep time. In:

Johns MW. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. PubMed DOI

Dauvilliers Y, Evangelista E, Barateau L, et al. Measurement of symptoms in idiopathic hypersomnia: the Idiopathic Hypersomnia Severity Scale. PubMed DOI

Chasens ER, Ratcliffe SJ, Weaver TE. Development of the FOSQ-10: a short version of the Functional Outcomes of Sleep Questionnaire. PubMed DOI PMC

Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. PubMed DOI PMC

Evangelista E, Lopez R, Dauvilliers Y. Update on treatment for idiopathic hypersomnia. PubMed DOI

Schinkelshoek MS, Fronczek R, Lammers GJ. Update on the treatment of idiopathic hypersomnia. DOI

Bogan RK, Roth T, Schwartz J, Miloslavsky M. Time to response with sodium oxybate for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. PubMed DOI PMC

Mayer G, Benes H, Young P, Bitterlich M, Rodenbeck A. Modafinil in the treatment of idiopathic hypersomnia without long sleep time–a randomized, double-blind, placebo-controlled study. PubMed DOI

Inoue Y, Tabata T, Tsukimori N. Efficacy and safety of modafinil in patients with idiopathic hypersomnia without long sleep time: a multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study. PubMed DOI

US Bureau of Labor Statistics. Household data annual averages. 47. Absences from work of employed full-time wage and salary workers by occupation and industry; 2022. Available from: https://www.bls.gov/cps/cpsaat47.htm. Accessed 14 July 2022.

Trotti LM, Ong JC, Plante DT, Friederich Murray C, King R, Bliwise DL. Disease symptomatology and response to treatment in people with idiopathic hypersomnia: initial data from the Hypersomnia Foundation registry. PubMed DOI PMC

Šonka K, Šusta M, Billiard M. Narcolepsy with and without cataplexy, idiopathic hypersomnia with and without long sleep time: a cluster analysis. PubMed DOI

Vernet C, Arnulf I. Idiopathic hypersomnia with and without long sleep time: a controlled series of 75 patients. PubMed DOI PMC

Wickwire EM, Verma T. Value and payment in sleep medicine. PubMed DOI PMC

Schneider L, Stevens J, Husain A, Ito D, Fuller DS, Macfadden W. Characteristics and disease burden of patients with idiopathic hypersomnia with and without long sleep time: the Real-World Idiopathic Hypersomnia Outcomes Study (ARISE) [abstract]. Presented at: Annual Scientific Meeting of the Associated Professional Sleep Societies; June 4-8, 2022; Charlotte, NC.

Saad R, Ben-Joseph R, Prince P, Stack C, Bujanover S, Taylor B. Utilization of diagnostic sleep testing prior to idiopathic hypersomnia diagnosis among US adults: a real-world claims analysis [abstract 499]. DOI

Lammers GJ, Bassetti CLA, Dolenc-Groselj L, et al. Diagnosis of central disorders of hypersomnolence: a reappraisal by European experts. PubMed DOI

Nevsimalova S, Susta M, Prihodova I, Maurovich Horvat E, Milata M, Sonka K. Idiopathic hypersomnia: a homogeneous or heterogeneous disease? PubMed DOI

Leu-Semenescu S, Louis P, Arnulf I. Benefits and risk of sodium oxybate in idiopathic hypersomnia versus narcolepsy type 1: a chart review. PubMed DOI

Xyrem

U.S. Xyrem Multicenter Study Group. A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. PubMed

U.S. Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. PubMed DOI

Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. PubMed DOI

Xyrem International Study Group. A double-blind, placebo-controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. PubMed DOI

Husain AM, Bujanover S, Ryan R, Scheckner B, Black J, Profant J. Incidence and duration of common, early-onset adverse events occurring during 2 randomized, placebo-controlled, phase 3 studies of sodium oxybate in participants with narcolepsy. PubMed DOI PMC

Bogan RK, Foldvary-Schaefer N, Skowronski R, Chen A, Thorpy MJ. Timing and duration of treatment-emergent adverse events in a clinical trial of lower-sodium oxybate in participants with narcolepsy with cataplexy [poster 486]. Presented at: Annual Meeting of the Associated Professional Sleep Societies; June 10-13, 2021.

Finniss DG, Kaptchuk TJ, Miller F, Benedetti F. Biological, clinical, and ethical advances of placebo effects. PubMed DOI PMC

Pascoe M, Bena J, Foldvary-Schaefer N. Effects of pharmacotherapy treatment on patient-reported outcomes in a narcolepsy and idiopathic hypersomnia cohort. PubMed DOI PMC