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: Not yet recruiting
• 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 (Estimated): 123
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: [email protected]

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Is a man or woman who 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 study entry. If currently taking oxybate medication, has an ESS score > 10 at the Baseline polysomnography Visit (after washout period).
• 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.

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.
• Has a history or presence of any unstable or clinically significant medical condition, 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.
• Is being treated with or has planned treatment with any central nervous system sedating agents, including but not limited to benzodiazepines or other sedating anxiolytics, sedating antidepressants, hypnotics, sedatives, neuroleptics, opioids, barbiturates, phenytoin, ethosuximide, medications containing valproic acid or its sodium salt (eg, Depakene® and Depakote®), other sedating antiseizure medications, melatonin, muscle relaxants, general anesthetics, or any other medication from which the participant experiences sedation.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score in Participants With IH and Narcolepsy Treated With XYWAV	Baseline up to End of Treatment (approximately 10-21 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient Global Impression of Change (PGI-C) Score in Participants With IH and Narcolepsy Treated With XYWAV (Overall, Sleep Inertia, and Fatigue)	End of Treatment (approximately 10-21 weeks)
Change From Baseline in the Level of Rested or Refreshed Upon Awakening in Participants With IH and Narcolepsy Treated With XYWAV (Sleep Diary)	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in Patient Global Impression of Severity (PGI-S) Score in Participants With IH and Narcolepsy Treated With XYWAV (Overall, Sleep Inertia, and Fatigue)	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in Idiopathic Hypersomnia Severity Scale (IHSS) Total Score in Participants With IH Treated With XYWAV	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in the Number of Stage Shifts of Sleep in Participants With Narcolepsy Treated With XYWAV	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in the Duration of Sleep Stages in Participants With Narcolepsy Treated With XYWAV	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in the Percentage of Sleep Stages in Participants With Narcolepsy Treated With XYWAV	Baseline up to End of Treatment (approximately 10-21 weeks)
Change From Baseline in the Number of Arousals and Awakenings in Participants With Narcolepsy Treated With XYWAV	Baseline up to End of Treatment (approximately 10-21 weeks)
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) In a Subset of Participants With Narcolepsy Treated With XYWAV	PK (optional for narcolepsy patients only): Predose, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour post-first dose and post-second 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	PK (optional for narcolepsy patients only): Predose, 0.5 hour, 0.75 hour, 1 hour, 1.5 hour post-first dose and post-second dose; 8 hour post-first dose

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

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): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

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