Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy

Kushida et al have recently published their findings of a phase 3 randomsed clinical trial (the REST-ON trial) of a once-nightly sodium oxybate administration (ON-SXB) ¹. While sodium oxybate is considered effective for treatment of cataplexy, daytime sleepiness and disrupted sleep due to narcolepsy ² the body of supporting evidence is not large. The highest dose of sodium oxybate (9g nocte) being the most commonly assessed dosage in the literature, however a range of dosages have been assessed with twice-nightly doses also present in some studies. The sample sizes of these studies are quite small across the board.

While the authors conclusions may have some opposition ³, their results are encouraging nevertheless.  In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n = 107) or placebo (n = 105) with all three doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement versus placebo (all p < 0.001). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis which was consistent with other studies. The authors final conclusion was that ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single night time dose.

1. Clete A Kushida, Colin M Shapiro, Thomas Roth, Michael J Thorpy, Bruce C Corser, Akinyemi O Ajayi, Russell Rosenberg, Asim Roy, David Seiden, Jordan Dubow, Yves Dauvilliers, Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy, Sleep, Volume 45, Issue 6, June 2022, zsab200, https://doi.org/10.1093/sleep/zsab200

1. Morgenthaler, T. I., Kapur, V. K., Brown, T., Swick, T. J., Alessi, C., Aurora, R. N., Boehlecke, B., Chesson, A. L., Jr, Friedman, L., Maganti, R., Owens, J., Pancer, J., Zak, R., & Standards of Practice Committee of the American Academy of Sleep Medicine (2007). Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep, 30(12), 1705–1711. https://doi.org/10.1093/sleep/30.12.1705

• Franck Skobieranda, Shawn Candler, Wayne Macfadden, Once-nightly sodium oxybate (FT218) in the treatment of narcolepsy: a letter to the editor commenting on the recent publication by C. Kushida et al, Sleep, Volume 45, Issue 6, June 2022, zsab292, https://doi.org/10.1093/sleep/zsab292