Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study.
Chad Ruoff,Todd J. Swick,Robert C. Doekel,Helene A. Emsellem,Neil T. Feldman,Russell Rosenberg,Gary Bream,Moise A. Khayrallah,Yuan Lu,Jed Black +9 more
TLDR
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.Abstract:
STUDY OBJECTIVES 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. METHODS 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. RESULTS 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%). CONCLUSIONS 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. CLINICAL TRIALS REGISTRATION Clinicaltrials.gov identifier NCT01681121.read more
Citations
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Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.
Claudio L. Bassetti,Antoine Roger Adamantidis,Denis Burdakov,Denis Burdakov,Denis Burdakov,Fang Han,Ulf Kallweit,Ramin Khatami,Frits Koning,Brigitte R. Kornum,Gert Jan Lammers,Roland S. Liblau,Pierre H. Luppi,Pierre H. Luppi,Geert Mayer,T. Pollmacher,Takeshi Sakurai,Federica Sallusto,Federica Sallusto,Thomas E. Scammell,Mehdi Tafti,Yves Dauvilliers,Yves Dauvilliers +22 more
TL;DR: Current understanding of how genetic, environmental and immune-related factors contribute to a prominent orexin signalling deficiency in patients with NT1 are focused on, along with uncertainties concerning the ‘narcoleptic borderland’, including narcolepsy type 2 (NT2).
Journal ArticleDOI
Solriamfetol for Excessive Sleepiness in Obstructive Sleep Apnea (TONES 3). A Randomized Controlled Trial.
Paula K. Schweitzer,Russell Rosenberg,Gary Zammit,Mark H. Gotfried,Dan Chen,Lawrence P. Carter,Hao Wang,Yuan Lu,Jed Black,Atul Malhotra,Kingman P. Strohl,Tones Study Investigators +11 more
TL;DR: Solriamfetol significantly increased wakefulness and reduced sleepiness in participants with obstructive sleep apnea and excessive sleepiness; most adverse events were mild or moderate in severity.
Journal ArticleDOI
A randomized study of solriamfetol for excessive sleepiness in narcolepsy.
Michael J. Thorpy,Colin M. Shapiro,Geert Mayer,Bruce C. Corser,Helene A. Emsellem,Giuseppe Plazzi,Dan Chen,Lawrence P. Carter,Hao Wang,Yuan Lu,Jed Black,Yves Dauvilliers +11 more
TL;DR: This phase 3 study evaluated the safety and efficacy of solriamfetol in narcolepsy with a single dose of JZP‐110.
Journal ArticleDOI
Solriamfetol for the Treatment of Excessive Sleepiness in OSA: A Placebo-Controlled Randomized Withdrawal Study
Patrick J. Strollo,Jan Hedner,Nancy A. Collop,Daniel G. Lorch,Dan Chen,Lawrence P. Carter,Yuan Lu,Lawrence Lee,Jed Black,Jean-Louis Pépin,Susan Redline,Markku Partinen,Olli Polo,Tarja Saaresranta,Christine Paschen,Lena Leissner,Bradley Block,Robert C. Doekel,Stephen P. Duntley,Guillermo Giangreco,Rachel J. Givelber,Andrew D. Krystal,Chitra Lal,Mitchell Lee,James Maynard,Daniel Norman,Russell Rosenberg,Vernon Rowe,Kathleen Sarmiento,Andrew Schreiber,Richard Schwab,David Seiden,Morteza Shamsnia,J. Catesby Ware +33 more
TL;DR: This study demonstrated maintenance of solriamfetol efficacy and safety over 6 weeks and common adverse events included headache, dry mouth, nausea, dizziness, and insomnia.
Journal ArticleDOI
Recently Approved and Upcoming Treatments for Narcolepsy
TL;DR: This review summarises the mechanisms of action, pharmacokinetics, efficacy, and safety/tolerability of recently approved and emerging treatments for narcolepsy.
References
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