Ph4 PSG Combined JZP258-407

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
Idiopathic Hypersomnia, Narcolepsy

Intervention / Treatment
-----------------
* Drug: JZP258 (XYWAV)


Participation Criteria
=================
Eligibility Criteria
-----------------
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 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JZP258<br>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)<br>* Initiate dosage per XYWAV label and titrate to variable dosage.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epworth Sleepiness Scale (ESS) Total Score in Participants With IH and Narcolepsy Treated With XYWAV |  | Baseline up to End of Treatment (approximately 10-36 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 10-36 weeks) | 
| 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 10-36 weeks) | 
| 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 10-36 weeks) | 
| Idiopathic Hypersomnia Severity Scale (IHSS) Total Score in Participants With IH Treated With XYWAV |  | Baseline up to End of Treatment (approximately 10-21 weeks) | 
| Number of Stage Shifts of Sleep in Participants With Narcolepsy Treated With XYWAV |  | Baseline up to End of Treatment (approximately 10-36 weeks) | 
| Duration of Sleep Stages in Participants With Narcolepsy Treated With XYWAV |  | Baseline up to End of Treatment (approximately 10-36 weeks) | 
| Percentage of Sleep Stages in Participants With Narcolepsy Treated With XYWAV |  | Baseline up to End of Treatment (approximately 10-36 weeks) | 
| Number of Arousals and Awakenings in Participants With Narcolepsy Treated With XYWAV |  | 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 |  | 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 |  | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Idiopathic Hypersomnia, Narcolepsy, Excessive daytime sleepiness, Polysomnography, JZP258, XYWAV, Oxybate