To explore the impact of low-sodium oxybate (LXB; Xywav^®) dosages >9 g/night on cognitive complaints, functional impairments, work productivity, and symptom severity in participants with narcolepsy who may benefit from higher LXB dosages, per investigator judgement.

Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment), a prospective, open-label study (NCT05875974), evaluated LXB effectiveness/safety in narcolepsy or idiopathic hypersomnia.

Participants with narcolepsy underwent screening, 8-day assessment on LXB 9 g/night (“9g”), 2–8-week gradual titration, 2-week stable-dose period (SDP), 8-day end-of-treatment period on the optimized dosage (total ≤12 g; “>9g”), and 2-week safety follow-up. Secondary outcomes included Patient Global Impression of Severity (PGI-S) and Change (PGI-C). Exploratory outcomes included British Columbia Cognitive Complaints Inventory (BC-CCI), Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), and Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP [narcolepsy]). LSM differences (with nominal P-values) were baseline adjusted.

Forty-eight participants enrolled/took LXB >9g (mean±SD age: 39.2±10.9 years; 62.5% female). Total LXB dosage (mean±SD) at SDP (n=45) was 11.1±1.0 g/night. PGI-S (n=44) endorsement of ‘severe’ overall disease (moderately/severe/extremely) was 61.4% (9g) versus 29.5% (>9g), with 92.3% of participants reporting overall disease improvement on PGI-C (n=39; minimally/much/very much). Mean±SE BC-CCI total scores decreased from 6.9±0.6 on 9g to 5.1±0.7 on >9g (n=44; LSM, −1.84; P=0.0004) with fewer participants reporting moderate-to-severe cognitive complaints (34.1% to 18.2%). Mean±SE 9g/>9g FOSQ-10 total scores were 13.6±0.6/14.8±0.6 (n=40; LSM, 1.3; P=0.0014). Mean±SE 9g/>9g WPAI:SHP values were: absenteeism (work time missed; n=20), 5.8%±1.8%/6.4%±2.2% (LSM, 0.7%; P=0.6602); presenteeism (impairment while working; n=20), 40.0%±5.8%/26.5%±4.9% (LSM, −13.5%; P=0.0058); overall work impairment (n=20), 42.6%±6.0%/30.1%±5.6% (LSM, −12.5%; P=0.0191); and activity impairment (n=37), 56.2%±4.4%/34.1%±4.8% (LSM, −22.2; P<0.0001). Treatment-emergent adverse events were consistent with known LXB safety profile.

Participants identified to optimize to LXB dosages >9 g/night experienced improvements (versus 9 g/night) in cognitive complaints, daily functioning, work productivity, and overall disease burden.