0752 JZP-258 Dose Titration and Transition from Sodium Oxybate in a Placebo-Controlled, Double-Blind, Randomized Withdrawal Study in Adult Participants With Narcolepsy With Cataplexy

Abstract

Introduction: Sodium oxybate (SXB) is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP‐258 is an oxybate product candidate (at same concentration as SXB) with 92% less sodium. JZP‐258 dose adjustment during titration was evaluated. Methods: At study entry, participants were taking SXB only, SXB+other anticataplectics, anticataplectics other than SXB, or were cataplexy treatment naive. JZP‐258 treatment began during a 12‐week, open‐label optimized treatment and titration period. Participants taking SXB only or SXB+other anticataplectics transitioned to JZP‐258 at the same gram‐for‐gram dose as SXB and titrated to an efficacious and tolerable (optimal) dose from weeks 3‐12. Participants taking other anticataplectics or who were anticataplectic naive initiated JZP‐258 at 4.5 g/night and were titrated to an optimal dose at 1‐1.5 g/night/week (maximum total dose, 9 g/night). A 2‐week stable‐dose period and 2‐week, double‐blind, randomized withdrawal period followed. Results: During the stable‐dose period, total nightly JZP‐258 dose (median [range]) was higher in participants taking SXB at study entry (SXB only, 7.5 g [4.5‐9.0], n=45; SXB +other anticataplectics, 9.0 g [6.0‐9.0], n=14) compared with those not taking SXB (other anticataplectics, 7.5 g [4.5‐9.0], n=23; anticataplectic naive, 7.0 g [3.0‐9.0], n=67), and dose adjustments were fewer. In most (69%) participants taking SXB at study entry who entered the stable‐dose period, no change in dose was required (median [range] number of adjustments was 0 ([0‐8]); for those with a change in dose, most changes were within one titration step (1.5 g/night). In participants not taking SXB at study entry, the median (range) number of adjustments was 3.0 (0‐7). Conclusions: Most participants taking SXB at study entry transitioned to JZP‐258 treatment at the same dose with retained effectiveness. Participants not previously taking SXB achieved a tolerable and efficacious dose of JZP‐258 after a median of 3 adjustments.