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

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

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.

Study Overview

• Status: Completed
• Conditions: Narcolepsy
• Intervention / Treatment: Drug: JZP-258

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • Wright Clinical Research, LLC
    • Birmingham, Alabama, United States, 35213
      • Sleep Disorders Center of Alabama
    • Birmingham, Alabama, United States, 35254
      • Pulmonary Associates of the Southeast, PC
  • California
    • Los Angeles, California, United States, 90048
      • Southern California Institute For Respiratory Diseases, Inc.
    • Los Angeles, California, United States, 90025
      • Santa Monica Clinical Trials
    • Los Angeles, California, United States, 90048
      • Southern California Institute For Respiratory Diseases, Inc./ Tower Sleep Medicine
    • Redwood City, California, United States, 94063
      • Stanford University- Sleep Medicine
    • Santa Ana, California, United States, 92705
      • SDS Clinical Trials, Inc
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves, Inc.
  • Florida
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialists, PA d/b/a PDS Research
    • Tampa, Florida, United States, 33606
      • Clinical Research of West Florida, Inc
    • Winter Park, Florida, United States, 32789
      • Florida Pediatric Research Institute, LLC
  • Georgia
    • Macon, Georgia, United States, 31210
      • Sleep Practitioners LLC
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Institute
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • The Center for Sleep & Wake Disorders
  • Michigan
    • Kalamazoo, Michigan, United States, 49008
      • WMed Center for Clinical Research
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Lung Center
  • Missouri
    • Saint Louis, Missouri, United States, 63123
      • Clayton Sleep Institute, LLC
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research LLC
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, Sleep Disorders Center
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine Institute
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Clinic
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants, LLC
    • North Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences
    • Rock Hill, South Carolina, United States, 29732
      • Clinical Research of Rock Hill
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age

1. Participant must be 18 to 80 years of age (inclusive), at the time of signing the informed consent. Type of Participant and Disease Characteristics
2. 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.

3. 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

4. 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

5. 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

1. Have a diagnosis of narcolepsy, secondary to another medical condition (eg, central nervous system injury or lesion)
2. Are currently prescribed a Xyrem regimen exceeding a dose of 9 grams nightly, or any single dose in excess of 6 grams.
3. Have been diagnosed with restless leg syndrome (RLS) requiring treatment other than iron supplements
4. Exhibit succinic semi-aldehyde dehydrogenase deficiency (SSADH)
5. Have uncontrolled hypothyroidism
6. Have a history of seizures, excluding early childhood non-pathological febrile seizures
7. 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

8. Show evidence of untreated or inadequately treated sleep-disordered breathing including:

   1. Presence of clinically significant and untreated obstructive or central sleep apnea (as determined by the investigator or documented previously); or one of the following:
   2. Apnea index (AI) >10 if on Obstructive Sleep Apnea (OSA) treatment or untreated, or
   3. Clinically significant hypoventilation, or
   4. 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.
9. 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.
10. Meet criteria for current major depression based on clinical interview
11. Have any clinically relevant medical, behavioral, or psychiatric disorder (other than narcolepsy) that is associated with excessive sleepiness
12. Have a history or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria
13. 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
14. Display relevant suicidality as indicated by Columbia Suicide Severity Rating Scale (C-SSRS) evaluation at screening
15. Display moderate to severe depression as indicated by the Participant Health Questionnaire - 9 (PHQ-9) at screening

16. Are a female participant who is pregnant or breastfeeding

    Prior/Concomitant Therapy

17. 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

18. 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.

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: Open-Label Conversion and Treatment Optimization; Conversion from Xyrem to XYWAV, maintaining the dose and regimen of any concomitant anticataplectics or stimulants unchanged throughout study.	Drug: JZP-258; Maximum nightly dosage of 9 grams, administered once, twice or thrice nightly, with no single dose > 6 g; Other Names: XYWAV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weekly Rate of Cataplexy Attacks	Mean weekly rate of cataplexy attack = (total number of cataplexy attacks reported during the period/number of days during the period where a diary was completed) x 7.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in the Nausea Visual Analog Scale (NVAS)	Tolerability associated with Xyrem and XYWAV was measured based on an NVAS assessment administered electronically. NVAS was captured daily during the last 7 days of the Baseline (Xyrem-stable dose and regimen) period and the last 7 days of the Intervention period (on XYWAV) prior to the ET visit or prior to the E/D visit, if possible. For participants with at least one day of NVAS data, the NVAS for that week was the average daily score from days with non-missing data within the week, then multiplied by 7. The NVAS ranges 0-100 mm, with higher scores representing more severe/intense nausea.	Baseline to Week 8
Number of Participants With Patient Global Impression of Change (PGIc) Values	The PGIc is a 7-point Likert-type rating based on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). PGIc values were measured at the ET or E/D, as applicable.	Week 8
Change in Epworth Sleepiness Scale (ESS)	The ESS questionnaire included a set of 8 questions regarding how likely the participant would be to doze off or fall asleep in different situations. The ESS measures EDS or average sleep propensity in daily life. Responses range from 0 = would never doze (better outcome) to 3 = high chance of dozing (worse outcome). Changes in ESS scores were assessed between the Baseline period and ET or E/D, as applicable	Baseline to Week 8
Number of Changes From the First Dose and Regimen to Optimized Dose and Regimen	The amount of times the dose and regimen were changed before an optimized dose and regimen were achieved.	Baseline to Week 8
Number of Participants Dosing Fasted Versus Dosing Without Consideration of Food	Once the participant reached an optimized dose and regimen, the investigator could decide to instruct the participant to dose without regard to 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	Types of meals consumed before dosing.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 12, 2021

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

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; Narcolepsy
• Other Study ID Numbers: JZP258-401

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
• product manufactured in and exported from the U.S.: No