Results of the phase 3 REST-ON study exhibited significant improvement in patients with narcolepsy treated with once-nightly sodium oxybate, FT218, versus placebo.
According to findings of the phase 3 REST-ON study, once-nightly sodium oxybate, called FT218, was shown to significantly improve symptoms of narcolepsy compared with placebo while also maintaining a safety profile similar to that of sodium oxybate.
In assessing the pharmacologic management of narcolepsy, sodium oxybate was noted by researchers as the only drug that has demonstrated efficacy across multiple narcolepsy symptoms, including disrupted nighttime sleep and excessive daytime sleepiness (EDS).
Although transformational for those who comply with the regimen, adherence can prove an issue as the therapy’s sedating nature requires twice-nightly dosing, with patients having to wake up 2.5 to 4 hours after the first dose to take the second dose.
“This forced awakening is disruptive to some patients and bed partners, especially considering that patients with narcolepsy typically already experience sleep fragmentation and poor sleep quality,” noted the study authors. “A serious adverse event resulting in hospitalization was reported due to accidentally ingesting the second dose of sodium oxybate immediately after the first dose.”
In prior research, FT218, an investigational, extended-release, once-nightly formulation of sodium oxybate, has been shown to be equivalent in systemic drug exposure when administered in a 6-g dose to immediate-release sodium oxybate given as 2 separate 3-g doses. Leveraging proprietary drug delivery technology, the treatment administers a single dose that provides an early single peak, followed by a gradual decline in sodium oxybate concentration.
Seeking to further examine the efficacy and safety of FT218, researchers randomized patients with narcolepsy aged 16 and older of the phase 3 REST-ON study to receive uptitration of the investigational therapy (4.5, 6, 7.5, and 9 g) or placebo at a 1:1 ratio (N = 212).
Participants were assessed for 3 co-primary endpoints, including change from baseline in mean sleep latency on the Maintenance of Wakefulness test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and weekly cataplexy attacks at 9, 7.5, and 6 g, with secondary endpoints of change from baseline on the Epworth Sleepiness Scale (ESS) evaluated as well.
In their findings, patients randomized to FT218 doses of 6-g and above exhibited clinically meaningful, statistically significant improvement in all 3 co-primary endpoints and ESS vs placebo (P < .001).
Comparing 9-g FT218 dosage vs placebo:
Exhibiting a safety profile consistent with sodium oxybate, common adverse reactions of FT218 included nausea, vomiting, headache, dizziness, and enuresis.
“Once-nightly sodium oxybate is under review at the FDA for the treatment of EDS and cataplexy in adults with narcolepsy with a Prescription Drug User Fee Act date of October 15, 2021,” concluded the study authors. “If approved, FT218 may represent a major advance for patients experiencing the burdensome symptoms of narcolepsy and for physicians who manage their patients with this chronic, debilitating sleep disorder.”
Kushida CA, Shapiro CM, Roth T, et al. Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy. Sleep. Published online August 6, 2021. doi:10.1093/sleep/zsab200