Poster
125
(#125) Greater Than 9 Gram Dosage of Low-Sodium Oxybate in Study Participants With Narcolepsy: Effectiveness and Safety Results From the DUET Study
Psych Congress 2025
Abstract: Introduction: Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment), a prospective, multicenter, multiple-cohort, single-arm, open-label study (NCT05875974), evaluated effectiveness/safety of low-sodium oxybate (LXB; Xywav®) in participants with narcolepsy (type 1 [NT1]; type 2 [NT2]) or idiopathic hypersomnia. The recommended LXB dosage range is 6-9 g/night. This analysis evaluated effectiveness/safety of LXB dosages >9 g/night (dosages >9 g/night have not been studied and ordinarily should not be administered) in participants with narcolepsy.
Methods: Participants underwent screening, 8-day baseline (BL) on LXB 9 g/night, 2-8-week gradual titration, 2-week stable-dose, 8-day end-of-treatment (EOT) on optimized total nightly dosage up to 12 g, and 2-week safety follow-up. Endpoints included Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale (NSS), apnea-hypopnea index (AHI), and mean oxygen saturation (SpO2). BL AHI >10 was exclusionary.
Results: Forty-eight participants took LXB in the >9-g cohort (mean±SD age: 39.2±10.9 years; 62.5% female). Mean±SD total LXB dosage (stable-dose period; n=45) was 11.1±1.0 g/night (46.7% at 12g/night). For completers (n=44), mean±SE BL/EOT ESS scores were 11.4±0.8/8.3±0.9. NT1 (n=26) mean±SE BL/EOT NSS scores were 17.3±2.2/9.4±2.1. NT2 (n=16) mean±SE BL/EOT NSS-2 scores were 9.7±1.7/4.3±1.6. Mean±SE BL/EOT AHI was 1.8±0.4/1.6±0.3; mean±SE SpO2 was 95.8±0.2/95.8±0.1. Common TEAEs (mostly mild/moderate) included nausea (12.5%), vomiting (12.5%), and headache (10.4%); 3 TEAEs were severe (hypnagogic hallucinations, nausea, syncope).
Conclusion: Participants taking LXB dosages >9 g/night experienced improvements in narcolepsy symptoms compared with BL (9 g/night). No changes in respiratory polysomnography measures were observed. TEAEs align with the safety profile at lower dosages, supporting individualized clinical decision-making.
Short Description: This poster shows that participants with narcolepsy from the phase 4, prospective, multicenter, single-arm, open-label, multiple-cohort DUET study (NCT05875974) treated with low-sodium oxybate dosages >9 g/night experience additional symptom benefit (reduced excessive daytime sleepiness and symptom burden) compared to treatment with 9 g/night (at baseline; approved recommended dosage is 6-9 g/night). Participants with narcolepsy taking LXB dosages >9 g/night maintained a similar safety profile as those taking ≤9 g/night (including no respiratory safety signals).
Name of Sponsoring Organization(s): Jazz Pharmaceuticals
Methods: Participants underwent screening, 8-day baseline (BL) on LXB 9 g/night, 2-8-week gradual titration, 2-week stable-dose, 8-day end-of-treatment (EOT) on optimized total nightly dosage up to 12 g, and 2-week safety follow-up. Endpoints included Epworth Sleepiness Scale (ESS), Narcolepsy Severity Scale (NSS), apnea-hypopnea index (AHI), and mean oxygen saturation (SpO2). BL AHI >10 was exclusionary.
Results: Forty-eight participants took LXB in the >9-g cohort (mean±SD age: 39.2±10.9 years; 62.5% female). Mean±SD total LXB dosage (stable-dose period; n=45) was 11.1±1.0 g/night (46.7% at 12g/night). For completers (n=44), mean±SE BL/EOT ESS scores were 11.4±0.8/8.3±0.9. NT1 (n=26) mean±SE BL/EOT NSS scores were 17.3±2.2/9.4±2.1. NT2 (n=16) mean±SE BL/EOT NSS-2 scores were 9.7±1.7/4.3±1.6. Mean±SE BL/EOT AHI was 1.8±0.4/1.6±0.3; mean±SE SpO2 was 95.8±0.2/95.8±0.1. Common TEAEs (mostly mild/moderate) included nausea (12.5%), vomiting (12.5%), and headache (10.4%); 3 TEAEs were severe (hypnagogic hallucinations, nausea, syncope).
Conclusion: Participants taking LXB dosages >9 g/night experienced improvements in narcolepsy symptoms compared with BL (9 g/night). No changes in respiratory polysomnography measures were observed. TEAEs align with the safety profile at lower dosages, supporting individualized clinical decision-making.
Short Description: This poster shows that participants with narcolepsy from the phase 4, prospective, multicenter, single-arm, open-label, multiple-cohort DUET study (NCT05875974) treated with low-sodium oxybate dosages >9 g/night experience additional symptom benefit (reduced excessive daytime sleepiness and symptom burden) compared to treatment with 9 g/night (at baseline; approved recommended dosage is 6-9 g/night). Participants with narcolepsy taking LXB dosages >9 g/night maintained a similar safety profile as those taking ≤9 g/night (including no respiratory safety signals).
Name of Sponsoring Organization(s): Jazz Pharmaceuticals
