"Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy"

A Twelve-week, Double-blind, Placebo-controlled, Randomized, Parallel-group, Multicenter Study of the Safety and Efficacy of JZP-110 [(R)-2-amino-3-phenylpropylcarbamate Hydrochloride] in the Treatment of Excessive Sleepiness in Subjects With Narcolepsy

This trial is a 12-week, randomized, double-blind, placebo controlled, multicenter, 4-treatment parallel group study of the safety and efficacy of JZP-110 in the treatment of excessive sleepiness in adult subjects with narcolepsy.

Study Overview

• Status: Completed
• Conditions: Narcolepsy
• Intervention / Treatment: Drug: JZP-110; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M4P 1P2
      • Toronto Sleep Institute
    • Toronto, Ontario, Canada, m5K 2A7
      • Toronto Psychiatric Research Foundation
    • Toronto, Ontario, Canada, M6J 3S3
      • Pediatric Sleep Research Inc.
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • CARSM Sleep Laboratory & Clinic
• Finland
  • Helsinki, Finland, 00420
    • Helsinki Sleep Clinic
• France
  • Lille, France, 59000
    • Hospital Roger Salengro
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Paris, France, 75004
    • Universite Paris 5 Hôtel-Dieu
• Germany
  • Berlin, Germany, 10117
    • Advanced Sleep Research GmbH
  • Kassel, Germany, 34131
    • Studienzentrum Wilhelmshoehe
  • Schwerin, Germany, 19053
    • Somni bene GmbH Institut für Medizinische Forschung und Schlafmedizin Schwerin GmbH
  • Bayern
    • Regensburg, Bayern, Germany, 93053
      • medbo Bezirksklinikum Regensburg Schlafmedizinisches Zentrum
  • North Rhine-Westphalia
    • Muenster, North Rhine-Westphalia, Germany, 48149
      • Universitaetsklinikum Muenster
• Netherlands
  • Noord Holland
    • Heemstede, Noord Holland, Netherlands, 2103 SW
      • Sleep Wake Center SEIN Heemstede
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Sleep Disorders Center of Alabama
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Pulmonary Associates
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
  • California
    • Los Angeles, California, United States, 90048
      • So Cal Institute for Respiratory Diseases, Inc.
    • Oceanside, California, United States, 92054
      • Pacific Sleep Medicine
    • Orange, California, United States, 92868
      • SDS Clinical Trials
    • Redwood City, California, United States, 94063
      • Stanford University Center for Narcolepsy
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc.
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Critical care Pulmonary & Sleep Associates, LLC
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Saint Petersburg, Florida, United States, 33707
      • Clinical Research Group of St. Petersburg
    • Winter Park, Florida, United States, 32789
      • Florida Pediatric Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory Sleep Center
    • Atlanta, Georgia, United States, 30342
      • Neurotrials
    • Macon, Georgia, United States, 31201
      • SleepMed of Central Georgia
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University, Feinberg School of Medicine
    • Chicago, Illinois, United States, 60612
      • University of Illinois Chicago, College of Nursing
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Veritas Clinical Specialties LTD
  • Kentucky
    • Louisville, Kentucky, United States, 40218
      • Kentucky Research Group
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • The Center for Sleep & Wake Disorders
  • Massachusetts
    • Newton, Massachusetts, United States, 24590
      • Neurocare, Inc.
  • Michigan
    • Sterling Heights, Michigan, United States, 48314
      • Clinical Neurophysiology Services
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Lung Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri
    • Saint Louis, Missouri, United States, 63143
      • Clayton Sleep Institute
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • New York University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Hickory, North Carolina, United States, 28602
      • Hickory Research Center
    • Huntersville, North Carolina, United States, 28078
      • Hickory Research Center, ARSM Research, LLC
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • North Coast Clinical Trials Inc.
    • Cincinnati, Ohio, United States, 45245
      • Sleep Management Institute
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44130
      • Southwest Cleveland Sleep Research Center
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine & Neuroscience Institute
    • Toledo, Ohio, United States, 43606
      • Mercy St. Anne & Mercy St. Charles Sleep Disorders Center
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Lowcountry Lung Critical Care
    • Columbia, South Carolina, United States, 29201
      • Sleep Med of South Carolina
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology LP
    • Houston, Texas, United States, 77063
      • Todd J. Swick
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Major Inclusion Criteria:

1. Males and females between 18 and 75 years of age, inclusive
2. Diagnosis of narcolepsy according to ICSD-3 or DSM-5 criteria
3. Body mass index from 18 to <45 kg/m2
4. Consent to use a medically acceptable method of contraception
5. Willing and able to provide written informed consent

Major Exclusion Criteria:

1. Female subjects who are pregnant, nursing, or lactating
2. Moderate or severe sleep apnea on the baseline PSG.
3. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness
4. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria
5. History or presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy, safety, PK assessments, or the ability of the subject to complete the trial per the judgment of the Investigator
6. History of bariatric surgery within the past year or a history of any gastic bypass procedure
7. Presence or history of significant cardiovascular disease
8. Use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness
9. Use of any medications that could affect the evaluation of cataplexy
10. Received an investigational drug in the past 30 days or five half-lives (whichever is longer)
11. Previous exposure to or participation in a previous clinical trial of JZP-110 (ADX-N05, R228060, YKP10A)
12. History of phenylketonuria (PKU) or history of hypersensitivity to phenylalanine-derived products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 75 mg of JZP-110; Once Daily Dosing	Drug: JZP-110
Active Comparator: 300 mg of JZP-110; Once Daily Dosing	Drug: JZP-110
Active Comparator: 150 mg JZP-110; Once Daily Dosing	Drug: JZP-110
Placebo Comparator: Placebo; Once Daily Dosing	Drug: Placebo oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ESS Score From Baseline to Week 12	Change in Epworth Sleepiness Scale (ESS) score from Baseline to Week 12. A negative change from baseline represents improvement in excessive sleepiness. The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. An analysis of covariance (ANCOVA) was used for the analysis of ESS scores. The response variable was the change in ESS score from baseline.	Baseline to Week 12
Change in Maintenance of Wakefulness Test (MWT) From Baseline to Week 12	Change in mean sleep latency time (in minutes) as determined from the first 4 trials of a 40-minute MWT from baseline to Week 12. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicating greater ability to stay awake; a positive change from baseline represents improvement in the sleep latency time. Mean sleep latency defined as the average of the first 4 MWT trials, if 3 or 4 of them are non-missing.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects Reported Improved on the Patient Global Impression of Change (PGIc) at Week 12	Percentage of subjects reported as improved (minimally, much, or very much) on the PGIc at Week 12. PGIc was rated by subjects and measures the change in their condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse	Baseline to Week 12
Change in Sleep Latency Time on MWT Trial 1 at Week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.	Change from baseline for sleep latency in MWT during trial 1 at week 12
Change in Sleep Latency Time on MWT Trial 2 at Week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.	Change from baseline for sleep latency in MWT during trial 2 at week 12
Change in Sleep Latency Time on MWT Trial 3 at Week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.	Change from baseline for sleep latency in MWT during trial 3 at week 12
Change in Sleep Latency Time on MWT Trial 4 at Week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.	Change from baseline for sleep latency in MWT during trial 4 at week 12
Change in Sleep Latency Time on MWT Trial 5 at Week 12	Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at Week 12.	Change from baseline for sleep latency in MWT during trial 5 at week 12
Change in the Mean Sleep Latency Time as Determined From the First 4 Trials of a 40-Minute MWT From Baseline to Week 4	Change in mean sleep latency time (in minutes) as determined from the first 4 trials of a 40-minute MWT from Baseline to Week 4.	Baseline to Week 4

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Publications and helpful links

General Publications

• Rosenberg R, Thorpy MJ, Dauvilliers Y, Schweitzer PK, Zammit G, Gotfried M, Bujanover S, Scheckner B, Malhotra A. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022 Jan 1;18(1):235-244. doi: 10.5664/jcsm.9550.
• Rosenberg R, Baladi M, Bron M. Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea. J Clin Sleep Med. 2021 Apr 1;17(4):711-717. doi: 10.5664/jcsm.9006. Erratum in: J Clin Sleep Med. 2021 Nov 1;17(11):2343.
• Dauvilliers Y, Shapiro C, Mayer G, Lammers GJ, Emsellem H, Plazzi G, Chen D, Carter LP, Lee L, Black J, Thorpy MJ. 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. CNS Drugs. 2020 Jul;34(7):773-784. doi: 10.1007/s40263-020-00744-2.
• Emsellem HA, Thorpy MJ, Lammers GJ, Shapiro CM, Mayer G, Plazzi G, Chen D, Carter LP, Villa KF, Lee L, Menno D, Black J, Dauvilliers Y. Measures of functional outcomes, work productivity, and quality of life from a randomized, phase 3 study of solriamfetol in participants with narcolepsy. Sleep Med. 2020 Mar;67:128-136. doi: 10.1016/j.sleep.2019.11.1250. Epub 2019 Dec 4.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 22, 2015
• First Posted (Estimate): January 28, 2015

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 21, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Sleepiness; Narcolepsy
• Other Study ID Numbers: 14-002