Objective:

To evaluate safety/efficacy data of once-nightly sodium oxybate (ON-SXB) in the long-term, open-label RESTORE (NCT04451668) study for participants who were not taking an oxybate at study entry.  

Background:

Treatment with ON-SXB met primary/secondary efficacy endpoints for excessive daytime sleepiness, cataplexy, overall condition, and disrupted nighttime sleep, with a safety profile consistent with twice-nightly oxybates (TN-OXB), in the phase 3 REST-ON trial. 

Design/Methods:

Participants were aged ≥16 years with narcolepsy who completed REST-ON, were oxybate-naive, or switched from stable (≥1 mo) TN-OXB. If not taking oxybate at entry, ON-SXB was initiated at 4.5 g/night; doses were adjusted by ±1.5 g/night weekly as needed up to 9 g/night. Adverse drug reactions (ADRs; ie, adverse events [AEs] related to ON-SXB) were collected. Epworth Sleepiness Scale (ESS), daily diary (weekly cataplexy episodes, nighttime awakenings), and Clinical and Patient Global Impression of Improvement (CGI-I; PGI-I) data were collected for participants not taking an oxybate at study entry.

Results:

REST-ON completers/oxybate-naive participants (N=50) were mean age 32.7 (range, 16-72) years; 60% were female and 80% were white. Median ON-SXB exposure was 408.1 (range, 8-1098) days; 8 participants discontinued owing to an AE. Most common ADRs (≥4 participants) included nausea (24%), somnolence (12%), dizziness (10%), paresthesia (8%), and tremor (8%). In the modified intent-to-treat (mITT) population (n=47), baseline mean (SD) ESS score was 14.4 (4.5); least squares mean (LSM) change from baseline (CFB) was -7.9 (95% CI, -10.1, -5.7; P<0.0001). Cataplexy episodes were significantly reduced (mITT, n=31; baseline mean [SD], 13.4 [10.1]; LSM CFB, -8.3 [95% CI, -12.1, -4.6; P=0.0003]). Nighttime awakenings were significantly reduced (baseline mean [SD], 15.8 [10.9]; LSM CFB, -7.2 [95% CI, -9.8, -4.7; P<0.0001]). Overall condition improved for most participants (CGI-I, 80%; PGI-I, 80%).

Conclusions: