0853 Sleep Architecture with Low-Sodium Oxybate Treatment in Idiopathic Hypersomnia: Results from the DUET Study

Abstract Introduction Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, multiple-cohort, open-label study (NCT05875974) evaluating the effectiveness of low-sodium oxybate (LXB, Xywav®) treatment on outcomes including polysomnography (PSG)-based sleep architecture in participants with idiopathic hypersomnia or narcolepsy. This abstract will include results from the idiopathic hypersomnia cohort. Methods DUET included a screening period (2-week washout for current oxybate users), an 8-day baseline (BL) period, a 2- to 8-week LXB titration period, a 2-week stable-dose period (SDP), an 8-day end-of-treatment period (EOT), and a 2-week safety follow-up. Participants underwent nocturnal PSG using an ad libitum protocol at BL and EOT. PSGs were scheduled to allow a minimum of 10 hours in bed, unless the participant naturally awakened earlier; bedtime was determined by habitual bedtime. PSG recordings were centrally scored. Data were analyzed for participants in the idiopathic hypersomnia cohort completer set. P-values were uncontrolled for multiplicity and therefore considered nominal. Results Forty-six participants with idiopathic hypersomnia enrolled; 40 completed the study. Most were female (80%) and White (85%) with a mean±SD age of 38.1±11.8 years. Mean±SD total sleep time (TST) at BL and EOT was 467.5±111.9 and 413.4±97.9 minutes, respectively (LSM change [95% CI], –54.1 [–81.3, –26.9]; P=.0003). Mean±SD number of total shifts from deeper to lighter sleep stages at BL and EOT was 60.8±30.1 and 43.7±27.0, respectively (LSM [95% CI], –17.1 [–23.7, –10.5]; P<.0001). Mean±SD time spent in N1 at BL and EOT was 47.8±26.1 and 33.0±22.4 minutes (LSM [95% CI], –14.8 [–20.3, –9.3]; P<.0001), % of stage was 10.3% and 8.0% (P=.0017); in N2, 270.0±64.8 and 225.8±72.8 minutes (LSM [95% CI], –44.3 [–66.7, –21.9]; P=.0003), 58.5% and 54.2% (P=.0286); in N3, 51.9±35.3 and 92.5±53.5 minutes (LSM [95% CI], 40.6 [25.8, 55.4]; P<.0001), 11.2% and 22.8% (P<.0001); and in REM, 97.7±47.0 and 62.1±35.4 minutes (LSM [95% CI], –35.7 [–46.0, –25.3]; P<.0001), 20.0% and 15.0% (P<.0001). Conclusion Participants with idiopathic hypersomnia treated with open-label LXB demonstrated reduced TST on ad libitum polysomnography compared with baseline, increases in N3 sleep, and changes in sleep architecture. Support (if any) Jazz Pharmaceuticals