Oral JZP-110 (ADX-N05) for the treatment of excessive daytime sleepiness in adults with narcolepsy: Results of a randomised, double-blind, placebo-controlled trial

Objective: Evaluate JZP‐110, a wake‐promoting agent with dopaminergic and noradrenergic activity, for treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy. Methods: This double‐blind, placebo‐controlled study randomised adults with narcolepsy to once‐daily placebo (n = 49) or JZP‐110 (n = 44) doses of 150 mg/day (weeks 1‐4) increased to 300 mg/day (weeks 5‐12). Efficacy endpoints included change from baseline in average sleep onset latency (SOL) on the 40‐min Maintenance of Wakefulness Test; Clinical Global Impression‐Change (CGI‐C); and change from baseline on the Epworth Sleepiness Scale (ESS). Results: Week 4 changes from baseline were significantly greater with JZP‐110 150 mg vs. placebo: increased SOL (9.5 vs 1.4 min; P < 0.0001), decreased ESS scores (5.6 points vs 2.4 points; P = 0.0038), and more patients with CGI‐C improvement (80% vs 51%; P = 0.0066). At week 12, following 8 weeks of 300 mg/day, JZP‐110 resulted in greater improvement from baseline than placebo on SOL (12.8 vs 2.1 min; P < 0.0001), ESS (8.5 points vs 2.5 points; P < 0.0001), and percentage of patients with CGI‐C improvement (86% vs 38%; P < 0.0001). Three subjects (6.8%) on JZP‐110 discontinued due to adverse events (AEs). The most common AEs with JZP‐110 vs placebo were headache (16% vs 10%), nausea (14% vs 6%), diarrhoea (11% vs 6%), insomnia (14% vs 2%), decreased appetite (14% vs 0%), and anxiety (11% vs 0%). Two serious AEs (conversion disorder, acute cholecystitis) in the JZP‐110 group were considered unrelated to treatment. Conclusion: In adults with narcolepsy, JZP‐110 doses of 150‐ 300 mg/day were well‐tolerated, and objective and subjective symptoms of EDS were significantly improved.