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SLEEP LATENCY RESPONSE WITH FT218, A ONCE-NIGHTLY SODIUM OXYBATE: POST-HOC RESPONDER ANALYSES FROM THE PHASE 3 REST-ON CLINICAL TRIAL

      TOPIC: Sleep Disorders
      TYPE: Original Investigations
      PURPOSE: Sodium oxybate is efficacious across multiple narcolepsy symptom domains, including excessive daytime sleepiness; currently approved formulations require twice-nightly dosing. The efficacy and safety of FT218, an investigational, extended-release formulation of once-nightly sodium oxybate (ON-SXB), were analyzed in adults with narcolepsy in the pivotal REST-ON trial (NCT02720744). ON-SXB treatment was associated with significant improvements vs placebo on the coprimary endpoints of Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement, and weekly cataplexy attacks at all 3 tested doses (6, 7.5, and 9 g; all P<0.001). This post hoc responder analysis from REST-ON assessed improvement in mean sleep latency on the MWT.
      METHODS: REST-ON was a 13-week, phase 3, double-blind, placebo-controlled, multicenter, randomized clinical trial. Participants with narcolepsy age ≥16 years were randomized 1:1 to receive ON-SXB (4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and then 9 g for 5 weeks) or matching placebo once nightly before bedtime. Efficacy and safety assessments were completed at the end of each dosing period. Mean sleep latency was measured using the MWT across 5 trials of up to 30 minutes each. The percentage of participants in each treatment arm whose sleep latency improved ≥5, ≥10, ≥15, and ≥20 min from baseline and percentage with a mean MWT=30 min was determined. Two-sided P-values were calculated (Fisher's exact test).
      RESULTS: In total, 212 participants enrolled in REST-ON (ON-SXB, n=107; placebo, n=105). Baseline mean (SD) sleep latency on the MWT was 5.0 (3.1) min and 4.7 (2.6) min for the ON-SXB and placebo arms, respectively. Mean MWT was =30 min for 5.7% vs 0% (P<0.05), 10.5% vs 1.3% (P<0.05), and 13.2% vs 5.1% (P=0.14) of participants receiving ON-SXB 6, 7.5, and 9 g vs placebo, respectively. A significantly greater proportion of participants in the ON-SXB treatment group had increased mean sleep latency vs placebo at the 6-g dose (week 3; ≥5 min, 57.5% vs 25.0%, P<0.001; ≥10 min, 35.6% vs 9.1%, P<0.001; ≥15 min, 18.4% vs 3.4%, P=0.001; ≥20 min, 10.3% vs 1.1%, P<0.01), 7.5-g dose (week 8; ≥5 min, 63.2% vs 28.2%, P<0.001; ≥10 min, 43.4% vs 11.5%, P<0.001; ≥15 min, 31.6% vs 3.8%, P<0.001; ≥20 min, 15.8% vs 1.3%, P<0.001), and 9-g dose (week 13; ≥5 min, 66.2% vs 37.2%, P<0.001; ≥10 min, 50.0% vs 19.2%, P<0.001; ≥15 min, 32.4% vs 10.3%, P<0.01; ≥20 min, 17.6% vs 6.4%, P<0.05).
      CONCLUSIONS: ON-SXB treatment was associated with significant improvement vs placebo as shown by the mean sleep latency on the MWT; significantly more participants who received ON-SXB than placebo experienced increased mean sleep latency ranging between ≥5 min to ≥20 min. This improvement was evident as early as week 3 at the 6-g dose and continued to improve for the 7.5- and 9-g doses at week 8 and 13, respectively.
      CLINICAL IMPLICATIONS: ON-SXB is an efficacious treatment for daytime sleepiness in adults with narcolepsy.
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