An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy

Study Overview
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Brief Summary
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The rationale for the interventional, open-label, single-arm design of JZP258-401 is to evaluate the clinical experience in participants with narcolepsy transitioning treatment from Xyrem to XYWAV.

Official Title
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A Phase 4 Multicenter, Open-label, Single-arm Study of Safety, Tolerability, Effectiveness and Treatment Optimization in Participants Switching From Xyrem to XYWAV for the Treatment of Narcolepsy

Conditions
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Narcolepsy

Intervention / Treatment
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* Drug: JZP-258


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age Participant must be 18 to 80 years of age (inclusive), at the time of signing the informed consent. Type of Participant and Disease Characteristics Participants who have a primary diagnosis of Type 1 or Type 2 narcolepsy that meets ICSD-3 criteria or DSM-5 criteria (Ruoff and Rye 2016), and are being currently treated with Xyrem, with or without additional anticataplectics or stimulants. Participants who have been taking Xyrem (with or without additional anticataplectics or stimulants eg, TCA, SNRI, SSRI, atomoxetine) in a stable dose and regimen for at least two months prior to screening, with evidence of clinical improvement on their current regimen, per the investigator's judgement. Only Xyrem will be substituted with XYWAV, with dose and regimen of any concomitant anticataplectics or stimulants remaining unchanged throughout the study. Sex and Contraceptive/Barrier Requirements Participant is male or female A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) as defined in Appendix 3 OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency, as described in Appendix 3, during the study Intervention period and for at least 7 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (serum) during screening. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Informed Consent Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria: Medical Conditions Have a diagnosis of narcolepsy, secondary to another medical condition (eg, central nervous system injury or lesion) Are currently prescribed a Xyrem regimen exceeding a dose of 9 grams nightly, or any single dose in excess of 6 grams. Have been diagnosed with restless leg syndrome (RLS) requiring treatment other than iron supplements Exhibit succinic semi-aldehyde dehydrogenase deficiency (SSADH) Have uncontrolled hypothyroidism Have a history of seizures, excluding early childhood non-pathological febrile seizures Have a history of head trauma associated with loss of consciousness in the past 5 years, or if the event occurred more than 5 years prior to screening and the participant experiences sequelae due to the event Show evidence of untreated or inadequately treated sleep-disordered breathing including: Presence of clinically significant and untreated obstructive or central sleep apnea (as determined by the investigator or documented previously); or one of the following: Apnea index (AI) >10 if on Obstructive Sleep Apnea (OSA) treatment or untreated, or Clinically significant hypoventilation, or Noncompliance with primary OSA therapy Note: Non-compliance is defined as positive airway pressure use of <4 hours per night on <70% of nights (<5 of 7 nights/week) per historical report (with investigator concurrence) of use of an oral appliance on <70% of nights (≥5 of 7 nights/week), or receipt of an effective surgical intervention for OSA symptoms. Experience parasomnias (eg, sleep walking, REM Sleep Behavior Disorder, etc.) considered by the investigator to negatively impact the conduct of the study. Parasomnia events associated with physical injury to the participant (or others) shall be discussed with the sponsor Medical Monitor. Meet criteria for current major depression based on clinical interview Have any clinically relevant medical, behavioral, or psychiatric disorder (other than narcolepsy) that is associated with excessive sleepiness Have a history or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria Have a history or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or history or presence of another neurological 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 Display relevant suicidality as indicated by Columbia Suicide Severity Rating Scale (C-SSRS) evaluation at screening Display moderate to severe depression as indicated by the Participant Health Questionnaire - 9 (PHQ-9) at screening Are a female participant who is pregnant or breastfeeding Prior/Concomitant Therapy Have undergone treatment with any prohibited central nervous system (CNS) agents, including but not limited to benzodiazepines, non-benzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics, opioids, barbiturates, phenytoin, ethosuximide, or MCT inhibitors, eg, diclofenac, valproate, ibuprofen, within 2 weeks prior to enrollment. Discontinuation for the purpose of study enrollment is permitted only if considered safe by the investigator and approved by the Medical Monitors. Prior/Concurrent Clinical Study Experience Received any other investigational drug within 30 days or five half-lives (whichever is longer) prior to screening, or plan to use an investigational drug (other than the study intervention) during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Conversion and Treatment Optimization<br>Conversion from Xyrem to XYWAV, maintaining the dose and regimen of any concomitant anticataplectics or stimulants unchanged throughout study. | Drug: JZP-258<br>* Maximum nightly dosage of 9 grams, administered once, twice or thrice nightly, with no single dose > 6 g<br>* Other names: XYWAV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Converted from Xyrem to XYWAV |  | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Epworth Sleepiness Scale (ESS) | Changes in ESS scores between the Baseline period and ET or E/D, as applicable | Baseline to Week 8 | 
| Number of Participants with Participant Global Impression of Change (PGIc) Values | PGIc values will be measured at the ET or E/D, as applicable. The number of participants with each response will be summarized. | Week 8 | 
| Time to Achieve Optimized Dose and Regimen | Defined as the time from the first dose and regimen to the optimized dose and regimen of XYWAV, where the optimized dose and regimen indicates the final dose and regimen that remains unchanged throughout the remainder of the Intervention period. | Baseline to Week 8 | 
| Number of Changes from the First Dose and Regimen to Optimized Dose and Regimen |  | Baseline to Week 8 | 
| Number of Participants Dosing Fasted Versus Dosing Without Consideration of Food |  | Baseline to Week 8 | 
| Duration of time between the last meal relative to dosing | The difference between the time of day that participants ate their last meal and the time of day participants take their first dose. | Baseline to Week 8 | 
| Characterization of Meals Relative to Dosing |  | Baseline to Week 8 | 
| Change in Weekly Rate of Cataplexy Attacks |  | Baseline to Week 8 | 
| Change in the Nausea Visual Analog Scale (NVAS) | Tolerability associated with Xyrem and XYWAV will be measured based on an NVAS assessment administered electronically. | Baseline to Week 8 |