A Study to Investigate the Effect of XYWAV on Sleepiness, Polysomnography, and Functional Outcomes in Participants With Idiopathic Hypersomnia or Narcolepsy

A Prospective, Open-Label, Single-Arm, Multicenter Study to Evaluate the Effect of Low-Sodium Oxybate Oral Solution (XYWAV) on Sleepiness, Polysomnography, and Functional Outcomes in Adult Participants Aged 18 to 75 Years With Idiopathic Hypersomnia or Narcolepsy

This study will assess the safety and efficacy of JZP258 (XYWAV) on sleepiness, polysomnography, and functional outcomes in patients with idiopathic hypersomnia (IH) or narcolepsy.

Study Overview

• Status: Completed
• Conditions: Narcolepsy; Idiopathic Hypersomnia
• Intervention / Treatment: Drug: JZP258 (XYWAV)

Detailed Description

This prospective, multicenter, single-arm, open-label interventional study will assess the safety and efficacy of JZP258 on sleepiness, polysomnography measurements (eg, sleep stage transitions, sleep patterns, and sleep quality), daytime and nighttime symptoms, pharmacokinetics (in narcolepsy), and patient-reported outcomes that include subjective sleep quality and quality of life in patients with IH or narcolepsy.

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Heritage Medical Research Clinic, University of Calgary
  • Ontario
    • Markham, Ontario, Canada, L3R 1A3
      • AMNDX Inc
    • Toronto, Ontario, Canada, M5S 3A3
      • Johda Tishon Inc
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Sleep Disorders Center of Alabama
  • Arizona
    • Scottsdale, Arizona, United States, 85253
      • Perseverance Research Center, LLC
  • California
    • Irvine, California, United States, 92604
      • Amnova Clinical Research
    • Lakewood, California, United States, 90805
      • Long Beach Research Institute
    • Los Angeles, California, United States, 90025
      • Santa Monica Clinical Trials
    • Redwood City, California, United States, 94063
      • Stanford School of Medicine
    • San Ramon, California, United States, 94583
      • TriValley Sleep Center
    • Santa Ana, California, United States, 92705
      • SDS Clinical Trials, Inc.
  • Florida
    • Brandon, Florida, United States, 33511
      • Meris Clinical Research, LLC
    • Miami, Florida, United States, 33176
      • PharmaDev Clinical Research Institute, LLC
    • Winter Park, Florida, United States, 32789
      • Florida Hospital for Children
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research, Inc.
    • Rincon, Georgia, United States, 31326
      • Centricity Research Rincon - DBA IACT Health Southeast Lung Associates Research
  • Massachusetts
    • Newtown, Massachusetts, United States, 02459
      • Neurocare, Inc., dba Neurocare Center for Research
  • Michigan
    • Sterling Heights, Michigan, United States, 48314
      • Clinical Neurophysiology Services, P.C.
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Lukes Hospital Medical Center
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
    • Huntersville, North Carolina, United States, 28078
      • Stern Research Partners, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus - Clinical Research Unit
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine and Neuroscience Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates, LTD
    • Scranton, Pennsylvania, United States, 18510
      • Geisinger Clinic
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants, LLC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Houston, Texas, United States, 77030
      • Comprehensive Sleep Medicine Associates
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center
    • Sugar Land, Texas, United States, 77479
      • Tricoastal Narcolepsy and Sleep Disorders Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Is 18 to 75 years of age (inclusive) at the time of signing the informed consent form (ICF)
• Has a primary diagnosis of IH meeting International Classification of Sleep Disorders, Third Edition (ICSD-3) criteria or narcolepsy (Type 1 or Type 2) meeting ICSD-3 or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.
• If not currently taking oxybate medication, has clinically significant symptoms of Excessive daytime sleepiness (EDS) with an ESS score > 10 at Screening Visit 1. If currently taking oxybate medication, has an ESS score > 10 at the Baseline Visit 2 polysomnography (after washout period). Note: Not applicable for participants entering the Narcolepsy >9-gram cohort (see additional criteria below for the Narcolepsy >9-gram cohort).
• If currently treated with anticataplectics and/or alerting agents, has been taking the same dosage for at least 1 month prior to Screening Visit 1 and has no current plans to adjust the dosage during the study period. Note: Alerting agents refer to either traditional stimulants (eg, amphetamines, methylphenidates) or wake-promoting agents (eg, modafinil, pitolisant, solriamfetol).

Additional Inclusion Criteria for Participants in the Exploratory Narcolepsy >9-Gram Cohort

• Is on a current treatment regimen including XYWAV at a dosage of 9 grams

Key Exclusion Criteria:

• Shows evidence of a previous untreated or inadequately treated sleep disorder considered by the investigator to negatively impact the conduct of the study, including sleep-disordered breathing, parasomnias, circadian rhythm sleep disorders, or restless legs syndrome determined by a previous sleep-laboratory diagnosis or interview utilizing modules of the Diagnostic Interview for Sleep Patterns and Disorders.
• Shows evidence of untreated or inadequately treated sleep-disordered breathing during Baseline Visit 2 polysomnography defined as an Apnea/Hypopnea Index (AHI) > 10, using the US Centers for Medicare and Medicaid Services rules (CMS.gov).
• Has a history or presence of any unstable or clinically significant medical condition (chronic pain condition that may impact sleep), behavioral or psychiatric disorder (including active suicidal ideation or current or past [within 1 year] major depressive episode), or history or presence of another neurologic disorder or surgical history that might affect the participant's safety and/or interfere with the conduct of the study, in the opinion of the investigator.

• Has recently taken (ie, within 1 month prior to screening), is taking, or plans to take any of the following:

  • A substance or medication contraindicated with XYWAV use, ie. specifically alcohol and sedative hypnotics
  • A medication with a known drug-drug interaction with XYWAV
  • A medication that may have similar EEG effects to XYWAV
  • Medications known to have clinically significant CNS sedative effects
  • Other medications, natural health products, or substances from which the participant experiences clinically significant sedation

Additional Exclusion Criterion for Participants in the Exploratory Narcolepsy >9-Gram Cohort

• Any past or current medical conditions or experience that, in the investigator's clinical judgment, would preclude further increases in the current oxybate medication dosage beyond 9 grams

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JZP258; Participants will self-administer an oral dose of JZP258 (XYWAV) as per label and titrate to an optimal dosage for each participant.	Drug: JZP258 (XYWAV); Narcolepsy Cohort: Initiate dosage per XYWAV label and titrate to effect. IH Cohort: Initiate dosage per XYWAV label and titrate to effect. Exploratory Narcolepsy >9-Gram Cohort: XYWAV titrated to a dosage of >9 to 12 grams.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score in Participants With IH and Narcolepsy Treated With XYWAV	The ESS total score (the sum of 8 item scores, each 0 to 3) can range from 0 to 24. Higher ESS total scores are associated with higher sleep propensity in daily life, also referred to as "daytime sleepiness."	Baseline up to End of Treatment (approximately 10-36 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Idiopathic Hypersomnia Severity Scale (IHSS) Total Score in Participants With IH Treated With XYWAV	The IHSS is a 14-item self-reported instrument that assesses the severity and functional consequences of IH symptoms. Questions capture symptoms of excessive sleepiness, sleep inertia, and long sleep duration. IHSS total scores range from 0 to 50 with higher score indicating worse clinical outcome.	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in Number of Stage Shifts of Sleep in Participants With Narcolepsy Treated With XYWAV	Stage shifts of sleep are defined as the count of transitions of bouts of sleep from deeper to lighter stages of sleep/wake (ie from N3/N2/N1/REM to wake and from N3/N2/REM to N1).	Baseline up to End of Treatment (approximately 10-36 weeks)
Change From Baseline in Duration of Sleep Stages in Participants With Narcolepsy Treated With XYWAV	Duration of sleep stages is measured in minutes (ie N1/N2/N3/REM) and is recorded from sleep onset to awakening during the nocturnal polysomnograph.	Baseline up to End of Treatment (approximately 10-36 weeks)
Change From Baseline in Number of Nocturnal Awakenings and Nocturnal Arousals in Participants With Narcolepsy Treated With XYWAV		Baseline up to End of Treatment (approximately 10-36 weeks)
Change From Baseline in Percentage of Sleep Stages in Participants With Narcolepsy Treated With XYWAV	The percentage of sleep stages is measured as minutes of each sleep stage (N3/N2/N1/REM) per hour of sleep time from sleep onset to awakening in the nocturnal polysomnograph.	Baseline up to End of Treatment (approximately 10-36 weeks)
Patient Global Impression of Change (PGI-C) in Participants With IH and Narcolepsy Treated With XYWAV (Overall, Sleep Inertia, and Fatigue)	The PGI-C is a single-item 7-point, Likert-type scale for rating change in disease or symptom severity. Responses for each question ranged from 1 (very much improved) to 7 (very much worse) relative to baseline. Participants rated the change from baseline in their overall (IH or narcolepsy) symptoms, sleep inertia (difficulty waking in the morning), and fatigue (extreme tiredness resulting from mental or physical exertion).	End of Treatment (approximately 10-36 weeks)
Level of Rested or Refreshed Upon Awakening in Participants With IH and Narcolepsy Treated With XYWAV (Sleep Diary)	The participant was asked "How rested or refreshed did you feel when you woke up for the day?"	Baseline up to End of Treatment (approximately 10-36 weeks)
Patient Global Impression of Severity (PGI-S) Score in Participants With IH and Narcolepsy Treated With XYWAV (Overall, Sleep Inertia, and Fatigue)	The PGI-S is a single-item, 7-point, Likert-type scale for rating disease or symptom severity. Responses ranged from 0 (not present) to 7 (extremely severe). Participants rated the severity of their overall (IH or narcolepsy) symptoms, sleep inertia, and fatigue. Higher scores indicate worse clinical outcome.	Baseline up to End of Treatment (approximately 10-36 weeks)
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) In a Subset of Participants With Narcolepsy Treated With XYWAV	Blood samples were processed to obtain plasma samples and then analyzed for oxybate concentrations using a validated bioanalytical method.	PK: Predose, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour post-first dose and post-second dose, 6 hour post-first dose, 8 hour post-first dose
Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) In a Subset of Participants With Narcolepsy Treated With XYWAV	Blood samples were processed to obtain plasma samples and then analyzed for oxybate concentrations using a validated bioanalytical method.	PK: Predose, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour post-first dose and post-second dose, 6 hour post-first dose, 8 hour post-first dose

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Publications and helpful links

General Publications

• Schneider LD, Ruoff CM, Plante DT, Nichols DA, Steininger TL, Fuller DS, Kirby MT, Akerman S, Alexander JK, Whalen M, Cairns A. Effectiveness and Safety of Low-Sodium Oxybate in Participants with Narcolepsy: Primary Results from the DUET Study. Neurol Ther. 2026 Aug;15(4):1613-1641. doi: 10.1007/s40120-026-00921-3. Epub 2026 Apr 30.
• Plante DT, Cairns A, Schneider LD, Nichols DA, Steininger TL, Fuller DS, Kirby MT, Akerman S, Alexander JK, Whalen M, Ruoff CM. Effectiveness and Safety of Low-Sodium Oxybate in Participants with Idiopathic Hypersomnia: Primary Results from the DUET Study. CNS Drugs. 2026 Jun;40(6):803-822. doi: 10.1007/s40263-025-01262-9. Epub 2026 Mar 14.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): March 13, 2025

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Polysomnography; Narcolepsy; Idiopathic Hypersomnia; Excessive daytime sleepiness; Oxybate; XYWAV; JZP258
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Disorders of Excessive Somnolence; Narcolepsy; Idiopathic Hypersomnia
• Other Study ID Numbers: JZP258-407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No