Low-Sodium Oxybate Reduces Excessive Sleep Time in Idiopathic Hypersomnia

Low-sodium oxybate (LXB; Xywav; Jazz Pharmaceuticals) was associated with significant reductions in total sleep time, nighttime sleep, and daytime napping in adults with idiopathic hypersomnia, according to a post hoc analysis of a phase 3 randomized-withdrawal trial.¹ During open-label treatment, median 24-hour total sleep time decreased by 39 minutes from baseline (P = .0005), with further evidence of treatment effect seen after randomization, as patients who switched to placebo experienced increases in overall sleep duration and nap time, whereas those continuing LXB remained stable.

Prolonged nighttime sleep and excessive total sleep time are hallmark features of idiopathic hypersomnia, a chronic neurologic sleep disorder associated with profound functional impairment.² LXB is currently the only treatment approved by the FDA for idiopathic hypersomnia, based on demonstrated efficacy and safety in a double-blind, placebo-controlled, randomized-withdrawal trial.³ This new post hoc analysis from that pivotal study examined how LXB affects sleep duration across the 24-hour day.¹

The analysis drew on data from a multicenter clinical trial (NCT03533114) that enrolled adults aged 18 to 75 years with a primary diagnosis of idiopathic hypersomnia. Participants initiated LXB during an open-label titration and optimization period lasting 10 to 14 weeks, followed by a 2-week stable-dose period. They were then randomized to either continue LXB or switch to placebo during a 2-week double-blind randomized-withdrawal period. Sleep outcomes were assessed using daily electronic sleep diaries, which captured 24-hour total sleep time (TST), nocturnal TST, and total nap duration.

After data cleaning to remove erroneous diary entries, 3917 valid daily records from 148 participants were included in the safety population, with 91 participants comprising the efficacy population. At baseline, more than half of the participants were taking concomitant alerting agents, and approximately 80% had idiopathic hypersomnia without long sleep time as judged by investigators.

During open-label LXB treatment, sleep duration decreased consistently across measures. From baseline to the end of the stable-dose period, median 24-hour TST fell from 513.3 minutes to 468.8 minutes, representing an estimated median reduction of 39 minutes. Median nocturnal TST declined from 495.0 to 454.3 minutes, while median total nap duration decreased from 16.3 minutes to 7.8 minutes. The average number of daily naps also dropped markedly, from 0.8 to 0.2 naps per day.

Reductions in sleep time were most pronounced among participants with longer baseline sleep durations. Those reporting less than 7 hours of baseline sleep showed slight increases in sleep time, whereas participants in higher baseline sleep categories (≥ 7 hours) experienced clear reductions in 24-hour and nocturnal sleep and in nap duration. Similar patterns were observed when participants were grouped by baseline sleep tertiles.

LXB-related decreases in sleep time were evident regardless of concomitant alerting agent use, although numerically larger reductions were observed in treatment-naïve participants. Sleep reductions were also more pronounced on nonworking days than on working days, suggesting that LXB particularly reduced excessive “catch-up” sleep on weekends or days off.

Across LXB dose categories during the stable-dose period, median 24-hour TST and total nap duration decreased at all dose levels, with statistically significant reductions most evident at higher nightly doses (7.5–9.0 g). Nocturnal TST showed modest decreases across dose groups.

The randomized-withdrawal phase provided further evidence of treatment effect. Participants who switched to placebo experienced a worsening of symptoms, with median 24-hour TST increasing by nearly 30 minutes and nap duration rising from 3.7 to 20.0 minutes. In contrast, participants who continued LXB maintained stable sleep durations. The estimated median difference between LXB and placebo was −25 minutes for 24-hour TST and −12 minutes for total nap duration.

Correlations between diary-based sleep measures and patient-reported outcomes on the Idiopathic Hypersomnia Severity Scale were generally weak to moderate, with the strongest associations observed between nocturnal sleep duration and patients’ perceived ideal sleep time.

LXB was generally well tolerated. The most common treatment-emergent adverse events (≥ 10% of participants) were nausea, headache, dizziness, anxiety, and vomiting, most of which were mild to moderate in severity.

Overall, this post hoc analysis shows that open-label treatment with LXB is associated with meaningful reductions in excessive total sleep time, nighttime sleep duration, and napping in adults with idiopathic hypersomnia, supporting its role in addressing one of the disorder’s core clinical features, the authors concluded.

References

1. Morse AM, Dauvilliers Y, Schneider LD, et al. Effects of low-sodium oxybate on diary-based sleep time in a clinical study in adults with idiopathic hypersomnia. Sleep Med. 2026;138:108710. doi:10.1016/j.sleep.2025.108710
2. Dauvilliers Y, Bogan RK, Arnulf I, Scammell TE, St Louis EK, Thorpy MJ. Clinical considerations for the diagnosis of idiopathic hypersomnia. Sleep Med Rev. 2022;66:101709. doi:10.1016/j.smrv.2022.101709
3. Gavidia M. FDA approves Jazz Pharmaceuticals’ Xywav for idiopathic hypersomnia. AJMC. August 12, 2021. Accessed February 11, 2026. https://www.ajmc.com/view/fda-approves-jazz-pharmaceuticals-xywav-for-idiopathic-hypersomnia