Poster
120
(#120) Effectiveness and Safety of Low-Sodium Oxybate in Participants With Narcolepsy With or Without Psychiatric Comorbidities: Results From the Phase 4 DUET Study
Psych Congress 2025
Abstract: Introduction: This post-hoc analysis of DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) evaluated effectiveness/safety of low-sodium oxybate (LXB; Xywav®) in participants with narcolepsy with or without psychiatric comorbidities (PsychCM; per medical history).
Methods: DUET included screening, 8-day baseline (BL), 2-8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT), and 2-week safety follow-up periods. Outcomes included Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scales (NSS; for narcolepsy types 1 and 2 [NT1/NT2]), Patient Global Impression of Change (PGI-C), and Patient Health Questionnaire-9 (PHQ-9). Least squares mean (LSM) changes were adjusted for baseline values.
Results: Fifty-five narcolepsy participants enrolled; 27 had concurrent PsychCM (most commonly depression and attention-deficit/hyperactivity disorder). Most participants (with/without PsychCM) were female (77.8%/67.9%) and White (92.6%/67.9%); thirty-four completed the study. Participants showed improved ESS and NSS scores from BL to EOT-LSM changes (95% CI): ESS, with PsychCM −8.3 (−10.8, −5.7), without PsychCM −6.9 (−9.8, −4.0); NSS-NT1, with PsychCM −22.0 (−27.7, −16.2), without PsychCM −17.2 (−23.4, −11.0); NSS-NT2, with PsychCM −12.3 (−16.6, −8.0), without PsychCM −9.5 (−15.2, −3.8). At EOT, a majority of participants (with/without PsychCM) reported "much"/"very much" PGI-C improvement for overall disease (82.4%/69.2%), and "none to minimal"/"mild" severity of depressive symptoms on PHQ-9 (88.9%/100.0%). Percentages of participants with/without PsychCM reporting ≥1 treatment-emergent adverse event (TEAE) were 76.9%/48.3%; common TEAEs included nausea, dizziness, and headache in both subgroups.
Conclusions: Results demonstrated effectiveness of LXB in participants with narcolepsy regardless of psychiatric comorbidities. TEAEs were consistent with the known LXB safety profile.
Short Description: This post hoc analysis of DUET (NCT05875974) evaluated the effectiveness/safety of low-sodium oxybate (LXB) treatment on narcolepsy in participants with or without psychiatric comorbidities. LXB-treated participants in both subgroups demonstrated improvements in Epworth Sleepiness Scale and Narcolepsy Severity Scales (NT1 and NT2) scores. Both subgroups showed improvements in Patient Global Impression of Change for overall disease and Patient Health Questionnaire-9 scores. Treatment-emergent adverse events in both subgroups were consistent with the known LXB safety profile.
Name of Sponsoring Organization(s): Jazz Pharmaceuticals
Methods: DUET included screening, 8-day baseline (BL), 2-8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT), and 2-week safety follow-up periods. Outcomes included Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scales (NSS; for narcolepsy types 1 and 2 [NT1/NT2]), Patient Global Impression of Change (PGI-C), and Patient Health Questionnaire-9 (PHQ-9). Least squares mean (LSM) changes were adjusted for baseline values.
Results: Fifty-five narcolepsy participants enrolled; 27 had concurrent PsychCM (most commonly depression and attention-deficit/hyperactivity disorder). Most participants (with/without PsychCM) were female (77.8%/67.9%) and White (92.6%/67.9%); thirty-four completed the study. Participants showed improved ESS and NSS scores from BL to EOT-LSM changes (95% CI): ESS, with PsychCM −8.3 (−10.8, −5.7), without PsychCM −6.9 (−9.8, −4.0); NSS-NT1, with PsychCM −22.0 (−27.7, −16.2), without PsychCM −17.2 (−23.4, −11.0); NSS-NT2, with PsychCM −12.3 (−16.6, −8.0), without PsychCM −9.5 (−15.2, −3.8). At EOT, a majority of participants (with/without PsychCM) reported "much"/"very much" PGI-C improvement for overall disease (82.4%/69.2%), and "none to minimal"/"mild" severity of depressive symptoms on PHQ-9 (88.9%/100.0%). Percentages of participants with/without PsychCM reporting ≥1 treatment-emergent adverse event (TEAE) were 76.9%/48.3%; common TEAEs included nausea, dizziness, and headache in both subgroups.
Conclusions: Results demonstrated effectiveness of LXB in participants with narcolepsy regardless of psychiatric comorbidities. TEAEs were consistent with the known LXB safety profile.
Short Description: This post hoc analysis of DUET (NCT05875974) evaluated the effectiveness/safety of low-sodium oxybate (LXB) treatment on narcolepsy in participants with or without psychiatric comorbidities. LXB-treated participants in both subgroups demonstrated improvements in Epworth Sleepiness Scale and Narcolepsy Severity Scales (NT1 and NT2) scores. Both subgroups showed improvements in Patient Global Impression of Change for overall disease and Patient Health Questionnaire-9 scores. Treatment-emergent adverse events in both subgroups were consistent with the known LXB safety profile.
Name of Sponsoring Organization(s): Jazz Pharmaceuticals
