A Randomized, Placebo-Controlled, Phase 3 Study of the Safety and Efficacy of Solriamfetol (JZP-110) for the Treatment of Excessive Sleepiness (ES) in Participants with Narcolepsy Types 1 and 2 (NT1/2) (CT.003)

Objective: Phase 3 study to assess safety and efficacy of solriamfetol in participants with narcolepsy types 1 and 2 (NT1/2).

Background: Solriamfetol is a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects. In 2 prior clinical studies, solriamfetol significantly improved wakefulness and reduced ES.

Design/Methods: A 12-week, double-blind, randomized, placebo-controlled, parallel-group study. Participants with or without cataplexy were randomized to receive solriamfetol 75 mg, 150 mg, 300 mg, or placebo for 12 weeks. Key eligibility criteria: NT1/2 diagnosis; mean sleep latency <25 minutes on the Maintenance of Wakefulness Test (MWT); Epworth Sleepiness Scale (ESS) score ≥10; nightly sleep time ≥6 hours. Key exclusion criteria: medications that could affect ES or cataplexy; nighttime or variable shift work; conditions besides NT1/2 that cause ES.

Results: Of 236 participants who received ≥1 dose of solriamfetol, 67.2% were female; 80.2% were white. Baseline ESS score was 17.2; baseline MWT mean sleep latency was 7.5 minutes. Solriamfetol significantly increased MWT sleep latency at week 12 (P<0.0001 for 300 mg and 150 mg). Least squares (LS) mean change from baseline to week 12 was 12.3 minutes for 300 mg, 9.8 for 150 mg, 4.7 for 75 mg, and 2.1 for placebo. Solriamfetol significantly decreased ESS scores at week 12 (P<0.0001 for 150 mg and 300 mg; P<0.05 for 75 mg). LS mean change from baseline in ESS was −6.4 for 300 mg, −5.4 for 150 mg, −3.8 for 75 mg, and −1.6 for placebo. Most common treatment-emergent adverse events (TEAEs; ≥5%) were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. One participant in solriamfetol 150 mg group had 2 serious TEAEs considered unrelated to study drug (continued in study without dose modification). Discontinuations due to TEAEs were more frequent in solriamfetol 150 mg and 300 mg groups.

Conclusions: Solriamfetol improved wakefulness and reduced ES in participants with NT1/2. Safety and tolerability were consistent with previous studies of solriamfetol.

Study Supported by:

Jazz Pharmaceuticals.

Disclosure: Dr. Thorpy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received consultancy fees from Jazz Pharmaceuticals, Merck & Co, Inc., and Teva Pharmaceutical Industries Ltd; and has been a member of the speakers’ bureau for Jazz Pharmaceuticals and Cephalon, Inc. (now Teva Pharmaceutical Industries, Ltd.). Dr. Thorpy has received research support from has received research/grant support and consultancy fees from Jazz Pharmaceuticals, Merck & Co, Inc., and Teva Pharmaceutical Industries Ltd. Dr. Shapiro has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with speakers’ bureau for Jazz Pharmaceuticals. Dr. Shapiro has received compensation for serving on the Board of Directors of board member, with stock/stock options, of Neurozone. Dr. Shapiro has received research support from received research funding from the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Mayer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with speakers’ bureaus for UCB Pharma and Sanofi. Dr. Mayer has received compensation for serving on the Board of Directors of a board member of the European Narcolepsy Network. Dr. Mayer has received research support from honoraria from the Paul Ehrlich Institute, Germany. Dr. Corser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with . BCC has received consultancy fees from and served on the speakers’ bureaus for Merck and Pernix. Dr. Emsellem has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received consultancy fees, honoraria, and/or has been a speakers’ bureau member for Jazz Pharmaceuticals, NightBalance, Philips North America, and Vanda Pharmaceuticals. Dr. Emsellem has received compensation for serving on the Board of Directors of is a board member of the National Sleep Foundation. Dr. Emsellem has received research support from has received research funding from Jazz Pharmaceuticals, Vanda Pharmaceuticals, Eisai, Flamel, and Merck & Co, Inc. Dr. Plazzi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Plazzi has participated in advisory boards for UCB and Jazz Pharmaceuticals. Dr. Chen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with DC is an employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with JL is an employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Carter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with LPC is an employee of Jazz Pharmaceuticals who, in the course of this employment, has received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with HW was an employee of Jazz Pharmaceuticals who, in the course of this employment, had received stock options exercisable for, and other stock awards of, ordinary shares of Jazz Pharmaceuticals plc. Dr. Black has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr Black is a part-time employee of Jazz Pharmaceuticals and shareholder of Jazz Pharmaceuticals plc. Dr. Dauvilliers has nothing to disclose.