0581 Patient Preferences and Nocturnal Experiences With Oxybate Therapy for Narcolepsy: RESTORE Study Interim Analysis

Abstract Introduction Sodium oxybate (SXB) is a standard-of-care treatment for adults with narcolepsy. Existing oxybate formulations are immediate release (IR), requiring patients to awaken for a second dose 2.5–4 hours after the first bedtime dose. Once-nightly SXB (ON-SXB; FT218), an investigational extended-release formulation, replaces this middle-of-the-night dosing with a once-at-bedtime regimen. RESTORE (NCT04451668) is an open-label/switch study evaluating the safety/tolerability of ON-SXB and patient preferences for ON-SXB or IR oxybate. Methods RESTORE includes participants aged ≥16 years with narcolepsy type 1 or 2 who completed the phase 3 REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive. Initial doses for participants switching from IR oxybate are equivalent/closest to the previous total dose/night; incremental adjustments (1.5 g/week; maximum, 9 g/night) are allowed. A nocturnal adverse event (AE) questionnaire about switch participants’ IR oxybate experience in the previous 3 months was completed at baseline. Switch participants completed the preference questionnaire after 3 months of ON-SXB treatment. Results Data available from preference questionnaires (n=78) and nocturnal AE questionnaires (n=130) were analyzed at the interim data cutoff (01 July 2022). Most common AEs thus far were nausea, headache, and somnolence. The once-nightly dosing regimen was preferred by 93.6% (73/78) of participants. The second nightly IR oxybate dose was unintentionally missed in the previous 3 months by 65.4% (85/130) of switch participants; 80.2% (73/91) who intentionally and/or unintentionally missed the second dose felt worse the next day. Participants who took their second nightly IR oxybate dose >4 h after the first dose (51/130 [39.2%]) reported being somewhat, quite a bit, or extremely groggy/unsteady the next morning (26/51 [51.0%]). Inconvenience of the second dose was reported by 70.8%. Other issues related to the second dose were anxiety (29.2%) and the need to be woken by someone else (23.1%). In the past 3 months, 118 participants (90.8%) arose from bed after waking to take the second dose; 9 of these participants reported having fallen, with 5 reporting injuries. Conclusion These interim RESTORE data demonstrate patient preference for once-at-bedtime dosing of ON-SXB and indicate treatment burden associated with twice-nightly IR oxybate. Support (if any) Avadel Pharmaceuticals