This study evaluated the effectiveness of low-sodium oxybate (LXB; Xywav^®) on daytime symptoms and functional impacts, including cognitive complaints and work productivity, in participants with narcolepsy or idiopathic hypersomnia (IH).

Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment) is a phase 4, prospective, multicenter, single-arm, open-label, multiple-cohort study (NCT05875974).

DUET comprised 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, 1- to 2-week end-of-treatment (EOT) period, and 2-week safety follow-up. The British Columbia Cognitive Complaints Inventory (BC-CCI) and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), both exploratory outcomes, were administered at BL and EOT.

Fifty-five participants with narcolepsy (72.7% female; 80.0% White) and 46 with IH (80.4% female; 85.0% White) took ≥1 dose of LXB after BL. BC-CCI total score improved from BL to EOT for narcolepsy, n=34 (mean [SD]: 8.9 [4.2] to 4.6 [3.4]; change score: −4.2 [4.0]) and IH, n=40 (10.1 [4.7] to 5.3 [4.4]; change score: −4.8 [4.0]). For narcolepsy, ratings of cognitive complaints at BL vs EOT, respectively, were “none or minimal,” 5 (14.7%) vs 18 (52.9%); “mild,” 12 (35.3%) vs 11 (32.4%); “moderate,” 14 (41.2%) vs 5 (14.7%); or “severe,” 3 (8.8%) vs 0 (0%). Respective cognitive complaint ratings for IH were “none or minimal,” 6 (15.0%) vs 19 (47.5%); “mild,” 11 (27.5%) vs 14 (35.0%); “moderate,” 16 (40.0%) vs 5 (12.5%); or “severe,” 7 (17.5%) vs 2 (5.0%). For WPAI:SHP, mean (SD) changes from BL to EOT were −36.1% (22.2%) and −32.4% (24.6%) for overall work impairment due to narcolepsy and IH, respectively. Treatment-emergent adverse events were consistent with the known LXB safety profile.

Open-label LXB treatment was associated with improvements in cognitive complaints and work productivity in participants with narcolepsy or IH.