A total of 190 participants were included in the mITT population (ON-SXB, n = 97; placebo, n = 93). The safety population included 212 participants (ON-SXB, n = 107; placebo, n = 105). Full participant demographics and disposition information have been previously published [14].

Baseline mean (SD) ESS scores were similar for participants receiving ON-SXB (16.6 [3.8]) and placebo (17.5 [4.1]). Numerical improvement with ON-SXB treatment compared with placebo was seen at week 1 with the 4.5-g dose (LSMD, − 0.7 [95% CI − 1.6 to 0.2]; P = 0.143; Fig. 2). A significant improvement in ESS score with ON-SXB treatment compared with placebo was observed at week 2 with the 6-g dose (LSMD, − 1.3 [95% CI − 2.4 to − 0.2]; P < 0.02).

Change from baseline in ESS score. ESS, Epworth Sleepiness Scale; LSM, least squares mean; LSMD, least squares mean difference; ON-SXB, once-nightly sodium oxybate (FT218). *P < 0.05; ***P < 0.001. Note: data for weeks 3–13 have been previously published [14]

For participants receiving ON-SXB and placebo, baseline mean (SD) sleep quality on the VAS was 53.8 (20.8) and 55.9 (22.6), respectively. Significantly greater improvement in sleep quality was observed with ON-SXB treatment relative to placebo at week 1 (LSMD, 3.6 [95% CI 1.1–6.1]; P < 0.01; Fig. 3) with the 4.5-g dose and at week 2 (LSMD, 7.0 [95% CI 3.8–10.1]; P < 0.001) with the 6-g dose.

Change from baseline in sleep quality. LSM, least squares mean; LSMD, least squares mean difference; ON-SXB, once-nightly sodium oxybate (FT218); VAS, visual analog scale. **P < 0.01; ***P < 0.001. Note: data for weeks 3–13 have been previously published [14]

Baseline mean (SD) refreshing nature of sleep on the VAS was 46.5 (21.8) and 49.9 (23.3) in the ON-SXB and placebo arms, respectively. Significantly greater improvement in the refreshing nature of sleep was observed with ON-SXB treatment relative to placebo at week 1 (LSMD, 3.2 [95% CI 0.5–5.9]; P < 0.05; Fig. 4) with the 4.5-g dose and at week 2 (LSMD, 5.8 [95% CI 2.3–9.4]; P = 0.001) with the 6-g dose.

Change from baseline in refreshing nature of sleep. LSM, least squares mean; LSMD, least squares mean difference; ON-SXB, once-nightly sodium oxybate (FT218); VAS, visual analog scale. *P < 0.05; ***P ≤ 0.001. Note: data for weeks 3–13 have been previously published [14]

At week 1 (4.5-g ON-SXB), the most common ADRs (≥ 5% of participants over time) among participants receiving ON-SXB (n = 107) were headache (6.5%), nausea (5.6%), dizziness (5.6%), decreased appetite (3.7%), vomiting (2.8%), anxiety (2.8%), and enuresis (1.9%) [14]. One participant per treatment arm experienced one SAE (ON-SXB, 0.9%, inadequate control of diabetes mellitus; placebo, 1.0%, drug hypersensitivity; both not related to study drug). Among the seven (6.5%) participants who discontinued ON-SXB owing to an AE at week 1 (4.5-g dose), the reported AEs included dizziness, anxiety, painful respiration, dysphagia, inadequately controlled diabetes mellitus, and delirium. Additionally, one (1.0%) participant receiving placebo discontinued at week 1 owing to an AE, which was identified as an allergic reaction to amoxicillin. At week 2 (6-g ON-SXB), the most common ADRs (≥ 5% of participants over time) in the ON-SXB treatment arm (n = 104) were nausea (5.8%), dizziness (3.8%), headache (3.8%), enuresis (3.8%), vomiting (2.9%), and decreased appetite (2.9%). One participant experienced an SAE of paresthesia (ON-SXB, 1.0%; not related to study drug). Three (3.1%) participants discontinued ON-SXB at week 2 (6-g dose) owing to an AE, which included nausea, enuresis, dyspnea, dizziness, headache, and restlessness. In the placebo group, one (1.0%) participant discontinued at week 2 owing to nausea, anxiety, and vomiting.