Solriamfetol for the Treatment of Excessive Daytime Sleepiness in Participants with Narcolepsy with and without Cataplexy: Subgroup Analysis of Efficacy and Safety Data by Cataplexy Status in a Randomized Controlled Trial

Abstract

Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, improved wakefulness and reduced excessive daytime sleepiness (EDS) in studies of participants with narcolepsy with and without cataplexy. Prespecified subgroup analyses of data from a 12-week randomized, double-blind, placebo-controlled, phase III trial of solriamfetol for EDS in narcolepsy evaluated the efficacy and safety of solriamfetol by cataplexy status. Participants with narcolepsy received solriamfetol (75, 150, or 300mg/day) or placebo and were stratified by cataplexy status. Coprimary endpoints were change from baseline on Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS); Patient Global Impression of Change (PGI-C) was the key secondary endpoint. Change in frequency of cataplexy attacks was evaluated in participants reporting cataplexy at baseline. Safety was evaluated. No adjustments were made for multiple comparisons; therefore p values are nominal. There were 117 participants in the cataplexy subgroup and 114 in the non-cataplexy subgroup. At week 12, least-squares (LS) mean (95% confidence interval [CI]) differences from placebo on change from baseline in MWT for solriamfetol 75, 150, and 300mg in the cataplexy subgroup were 1.6 (-3.6 to 6.9), 6.1 (0.7-11.4), and 8.9 (3.5-14.2) minutes, respectively (p < 0.05; 150 and 300mg), and in the non-cataplexy subgroup were 3.4 (-1.9 to 8.7), 9.1 (3.8-14.3), and 11.2 (5.8-16.6) minutes, respectively (p < 0.001; 150 and 300mg). At week 12, LS mean (95% CI) differences from placebo on ESS change from baseline for solriamfetol 75, 150, and 300mg in the cataplexy subgroup were -1.3 (-3.9 to 1.3), -3.7 (-6.4 to -1.1), and -4.5 (-7.1 to -1.9), respectively (p < 0.01; 150 and 300mg), and in the non-cataplexy subgroup were -3.0 (-5.6 to -0.4), -3.7 (-6.3 to -1.2), and -4.9 (-7.6 to -2.2), respectively (p < 0.05; all doses). For PGI-C at week 12, the mean percentage difference from placebo (95% CI) for solriamfetol 75, 150, and 300mg in the cataplexy subgroup was 10% (-15 to 35), 33% (9-57), and 39% (16-61), respectively (p < 0.05; 150 and 300mg), and in the non-cataplexy subgroup was 48% (25-70), 44% (21-67), and 52% (30-73), respectively (p < 0.001; all doses), with somewhat differential treatment effects for 75mg by cataplexy status. No changes in the number of cataplexy attacks were observed for solriamfetol compared with placebo (mean ± standard deviation changes: -3.6 ± 13.3 [combined solriamfetol] and -3.5 ± 9.8 [placebo]). Common adverse events (headache, nausea, decreased appetite, and nasopharyngitis) were similar between cataplexy subgroups. These data strongly indicate that solriamfetol was effective in treating EDS in participants with narcolepsy with or without cataplexy, as indicated by robust effects on MWT, ESS, and PGI-C. The safety profile was similar regardless of cataplexy status. ClinicalTrials.gov NCT02348593. 28 January 2015.