title: Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study.
abstract: To evaluate the efficacy and safety of oral JZP-110, a second-generation wake-promoting agent with dopaminergic and noradrenergic activity, for treatment of impaired wakefulness and excessive sleepiness in adults with narcolepsy.
  
  
  
  This was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 28 centers in the United States. Patients were adults with narcolepsy who had baseline scores ≥ 10 on the Epworth Sleepiness Scale (ESS) and baseline sleep latency ≤ 10 min on the Maintenance of Wakefulness Test (MWT). Patients received a daily placebo (n = 49) or JZP-110 (n = 44) 150 mg/day weeks 1-4 and 300 mg/day weeks 5-12. Primary efficacy endpoints were change from baseline in average MWT sleep latency, and the Clinical Global Impression-Change (CGI-C); secondary endpoints were change from baseline in ESS score and Patient Global Impression-Change.
  
  
  
  Improvements were significantly greater with JZP-110 versus placebo on mean MWT sleep latency (4 w, 9.5 versus 1.4 min, P < 0.0001; 12 w, 12.8 versus 2.1 min, P < 0.0001), percentage of patients with CGI-C improvement (4 w, 80% versus 51%, P = 0.0066; 12 w, 86% versus 38%, P < 0.0001), and mean change in ESS (4 w, -5.6 versus -2.4, P = 0.0038; 12 w, -8.5 versus -2.5, P < 0.0001). Three JZP-110-treated patients (6.8%) discontinued due to adverse events (AEs). The most common AEs with JZP-110 versus placebo were insomnia (23% versus 8%), headache (16% versus 10%), nausea (14% versus 6%), diarrhea (11% versus 6%), decreased appetite (14% versus 0%), and anxiety (11% versus 0%).
  
  
  
  At doses of 150-300 mg/day, JZP-110 was well tolerated and significantly improved the ability to stay awake and subjective symptoms of excessive sleepiness in adults with narcolepsy.
  
  
  
  Clinicaltrials.gov identifier NCT01681121.
authors.affiliation: Stanford University Sleep Medicine Center, Redwood City, CA.
authors.forename: Chad
authors.initials: C
authors.lastname: Ruoff
authors.affiliation: Neurology and Sleep Medicine Consultants of Houston, University of Texas-Houston School of Medicine, Houston, TX.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Swick
authors.affiliation: Sleep Disorders Center of Alabama, Birmingham, AL.
authors.forename: Robert
authors.initials: R
authors.lastname: Doekel
authors.affiliation: The Center for Sleep & Wake Disorders, Chevy Chase, MD.
authors.forename: Helene A
authors.initials: HA
authors.lastname: Emsellem
authors.affiliation: St Petersburg Sleep Disorders Center at Palms of Pasadena Hospital, St Petersburg, FL.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Feldman
authors.affiliation: NeuroTrials Research, Atlanta, GA.
authors.forename: Russell
authors.initials: R
authors.lastname: Rosenberg
authors.affiliation: Aerial BioPharma, Morrisville, NC.
authors.forename: Gary
authors.initials: G
authors.lastname: Bream
authors.affiliation: Aerial BioPharma, Morrisville, NC.
authors.forename: Moise A
authors.initials: MA
authors.lastname: Khayrallah
authors.affiliation: Jazz Pharmaceuticals, Inc., Palo Alto, CA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Stanford University Sleep Medicine Center, Redwood City, CA.|Jazz Pharmaceuticals, Inc., Palo Alto, CA.
authors.forename: Jed
authors.initials: J
authors.lastname: Black
mesh_terms: D000328:Adult; D000368:Aged; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000188:drug therapy* / Q000503:physiopathology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012894:Sleep Stages / Q000187:drug effects; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects; D064690:Wakefulness-Promoting Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002219:Carbamates; D064690:Wakefulness-Promoting Agents; D010649:Phenylalanine; C000623308:solriamfetol
keywords: JZP-110; excessive sleepiness; narcolepsy; wakefulness