0589 Dose Titration of Once-Nightly Sodium Oxybate: Analysis of Interim Data From RESTORE Free

FT218 (LUMRYZ™) is an investigational once-nightly sodium oxybate (ON-SXB) for treatment of adults with narcolepsy type 1 (NT1) or type 2 (NT2). The efficacy and safety of ON-SXB at doses 6, 7.5, and 9 g in patients with NT1/NT2 were confirmed in the phase 3 REST-ON clinical trial (NCT02720744). RESTORE is an ongoing, open-label extension/switch study to assess long-term safety and tolerability of ON-SXB (NCT04451668).

Individuals aged ≥16 years with NT1/NT2 are enrolled in Group A (participants who completed the REST-ON trial with no current oxybate use), Group B (participants who switched from twice-nightly immediate-release oxybates), or Group C (participants who are oxybate-naive). Initial ON-SXB dose is 4.5 g/night for Groups A/C and is the nearest equivalent or closest single dose to their previous nightly dose for Group B. Investigators may alter the nightly dose by 1.5 g/week (maximum, 9 g/night) based on effectiveness and tolerability.

A total of 184 participants were enrolled (180, ≥1-dose) as of July 1, 2022. Most participants are white (n=150 [83.3%]) and female (n=122 [67.8%]), and mean age is 35 years. Most participants in Groups A/C (n=43/50 [86.0%]) increased from the 4.5-g initial dose and had 2–4 dose adjustments during initial titration (median [range], 3 [0–5]); 47% (17/36) are stable at 7.5 g. The most common initial doses in Group B were 7.5 g (50/130 [38.5%]) and 9 g (47/130 [36.2%]). Most in Group B reaching a stable dose maintained their initial dose (70/118 [59.3%]); 43 increased (36.4%) and 5 decreased (4.2%) their initial ON-SXB dose. In Group B, 49.1% (53/108) had no dose adjustments (median [range], 1 [0–5]) and 83.0% (n=39/47) who started at 9 g maintained this dose. Most common treatment-related adverse events (>3%; safety population [n=180]) are nausea (11.7%), somnolence (6.7%), headache (5.0%), enuresis (5.0), dizziness (3.9%), tremor (3.9%), somnambulism (3.9%), and vomiting (3.3%).

Most study participants had successful titration of ON-SXB to a therapeutic and tolerable dose within 1 month. If granted final approval by the US Food and Drug Administration, ON-SXB will offer a once-nightly treatment for adults with narcolepsy.

Avadel Pharmaceuticals