0862 Sleep Architecture with Low-Sodium Oxybate Treatment in Narcolepsy: 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 effectiveness of low-sodium oxybate (LXB, Xywav®) treatment on outcomes including polysomnography (PSG)-based sleep architecture in participants with idiopathic hypersomnia or narcolepsy (type 1 [NT1] or 2 [NT2]). Methods DUET included a screening period (2-week washout for current oxybate users), 8-day baseline (BL) period, 2- to 8-week LXB titration period, 2-week stable-dose period (SDP), 8-day end-of-treatment period (EOT), and 2-week safety follow-up. Participants underwent nocturnal PSG (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 narcolepsy cohort completer set. Total shifts from deeper to lighter sleep stages was defined as N1/N2/N3/REM to wake and N2/N3/REM to N1. Key secondary endpoints (total stage shifts, N3 duration) were controlled for multiplicity with sequential testing; other P-values are considered nominal. Results Fifty-five participants with narcolepsy enrolled (NT1, n=26; NT2, n=29); 34 completed the study (NT1, n=16; NT2, n=18). Most were female (73%) and White (80%) (mean±SD age, 33.4±12.9 years). Mean±SD total sleep time (TST) at BL/EOT was 453.2±80.1/452.4±70.0 minutes (LSM change [95% CI]: –0.78 [–23.7, 22.1]; P=.9451). Mean±SD number of total shifts from deeper to lighter sleep stages at BL/EOT was 54.6±28.0/41.6±25.6 (LSM [95% CI]: –13.1 [–19.0, –7.1]; P<.0001 [controlled for multiplicity]). Mean±SD time spent in N1 at BL/EOT was 45.3±28.4/37.2±25.2 minutes (LSM [95% CI]: –8.1 [–14.9, –1.4]; P=.0196), % of stage was 10.4%/8.2% (P=.0037); in N2 was 241.8±61.2/243.3±76.1 minutes (LSM [95% CI]: 1.5 [–23.6, 26.6]; P=.9040), 53.1%/53.2% (P=.9869); in N3 was 61.1±34.8/106.1±69.5 minutes (LSM [95% CI]: 45.0 [27.0, 63.0]; P<.0001 [controlled for multiplicity]), 13.7%/24.0% (P<.0001); and in REM was 105.0±42.7/65.8±33.1 minutes (LSM [95% CI]: –39.2 [–50.8, –27.5]; P<.0001), 22.8%/14.7% (P<.0001). Conclusion Participants with narcolepsy taking open-label LXB showed negligible change in TST and N2, increased N3, decreased N1 and REM, and fewer shifts from deeper to lighter stages of sleep. Support (if any) Jazz Pharmaceuticals