Abstract Introduction Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) was the first study to evaluate effectiveness/safety of low-sodium oxybate (LXB; Xywav®) 9 g/night (outside the recommended range: 6–9 g/night). This analysis evaluated changes in patient-reported hypersomnolence measures in participants with narcolepsy taking LXB 9 g/night compared with LXB 9 g/night. Methods DUET was a phase 4, prospective, open-label study with screening, 8-day LXB 9 g/night (9g-baseline), titration/optimization, stable-dose, and 8-day end-of-treatment (EOT) optimized LXB 9 g/night (up to 12g; 9g-EOT) periods. Patient-reported measures included Epworth Sleepiness Scale (ESS), electronic sleep diaries (completed daily during 9g-baseline and 9g-EOT; subjective total sleep time TST, number of awakenings, sleep efficiency TST divided by time in bed, sleep quality 5-point scale; “very good” to “very poor”, and how rested/refreshed the participant felt upon awakening 5-point scale; “very well” to “not at all”), Karolinska Sleepiness Scale (KSS; administered 90 minutes post-polysomnography awakening at 9g-baseline and 9g-EOT), and Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10). LSM differences (95% CI) from 9g-baseline to 9g-EOT (nominal P-values) were 9g-baseline-adjusted. Results Forty-eight participants took LXB 9g (mean±SD age: 39.2±10.9 years; 62.5% female). Total stable-dose LXB (mean±SD) was 11.1±1.0 g/night (n=45). From 9g-baseline to 9g-EOT, ESS scores improved (LSM 95% CI: –3.1 –4.2, –1.9; P 0.0001; n=44), nocturnal TST increased (0.3h 0.1, 0.4; P=0.0163; n=26), sleep efficiency increased (3.8% 1.7, 5.9; P=0.0011; n=26), and number of awakenings remained stable (–0.2 –0.7, 0.3; P=0.3959; n=26). Percentage of participants rating sleep quality as “very good”/”good” increased from 26.9% (9g-baseline) to 61.5% (9g-EOT), as did rested sleep (“very well”/”well”/”somewhat” rested) from 57.7% to 69.2%, respectively. From 9g-baseline to 9g-EOT, KSS scores decreased (–0.9 –1.4, –0.4; P=0.0004; n=39); FOSQ-10 scores also increased (1.3 0.5, 2.0; P=0.0014; n=40). Of 48 participants, 36 (75.0%) experienced ≥1 TEAE (mostly mild/moderate and 1 serious syncope, unrelated to treatment). No changes in respiratory polysomnography measures were observed. Conclusion Participants with narcolepsy who optimized to LXB 9 g/night, relative to 9 g/night, reported increased sleep quality and restfulness that paralleled improvements in daytime sleepiness and daytime functioning. TEAEs were consistent with those at lower dosages. Support (if any) Jazz Pharmaceuticals
BOGAN et al. (Fri,) studied this question.