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

NCT ID: NCT04794491

Last Updated: 2024-01-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-22

Study Completion Date

2022-11-15

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.

Detailed Description

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Conditions

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Narcolepsy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

JZP-258

Intervention Type DRUG

Maximum nightly dosage of 9 grams, administered once, twice or thrice nightly, with no single dose \> 6 g

Interventions

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JZP-258

Maximum nightly dosage of 9 grams, administered once, twice or thrice nightly, with no single dose \> 6 g

Intervention Type DRUG

Other Intervention Names

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XYWAV

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Wright Clinical Research, LLC

Alabaster, Alabama, United States

Site Status

Sleep Disorders Center of Alabama

Birmingham, Alabama, United States

Site Status

Pulmonary Associates of the Southeast, PC

Birmingham, Alabama, United States

Site Status

Santa Monica Clinical Trials

Los Angeles, California, United States

Site Status

Southern California Institute For Respiratory Diseases, Inc./ Tower Sleep Medicine

Los Angeles, California, United States

Site Status

Southern California Institute For Respiratory Diseases, Inc.

Los Angeles, California, United States

Site Status

Stanford University- Sleep Medicine

Redwood City, California, United States

Site Status

SDS Clinical Trials, Inc

Santa Ana, California, United States

Site Status

Delta Waves, Inc.

Colorado Springs, Colorado, United States

Site Status

Pulmonary Disease Specialists, PA d/b/a PDS Research

Kissimmee, Florida, United States

Site Status

Clinical Research of West Florida, Inc

Tampa, Florida, United States

Site Status

Florida Pediatric Research Institute, LLC

Winter Park, Florida, United States

Site Status

Sleep Practitioners LLC

Macon, Georgia, United States

Site Status

Clinical Research Institute

Stockbridge, Georgia, United States

Site Status

The Center for Sleep & Wake Disorders

Chevy Chase, Maryland, United States

Site Status

WMed Center for Clinical Research

Kalamazoo, Michigan, United States

Site Status

Minnesota Lung Center

Edina, Minnesota, United States

Site Status

Clayton Sleep Institute, LLC

St Louis, Missouri, United States

Site Status

Clinical Research of Gastonia

Gastonia, North Carolina, United States

Site Status

Intrepid Research LLC

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic, Sleep Disorders Center

Cleveland, Ohio, United States

Site Status

Ohio Sleep Medicine Institute

Dublin, Ohio, United States

Site Status

Geisinger Clinic

Danville, Pennsylvania, United States

Site Status

Bogan Sleep Consultants, LLC

Columbia, South Carolina, United States

Site Status

Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences

North Charleston, South Carolina, United States

Site Status

Clinical Research of Rock Hill

Rock Hill, South Carolina, United States

Site Status

FutureSearch Trials of Neurology

Austin, Texas, United States

Site Status

Sleep Therapy & Research Center

San Antonio, Texas, United States

Site Status

Countries

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United States

References

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Macfadden W, Leary EB, Fuller DS, Kirby MT, Roy A. Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal Grams of Uninterrupted Xyrem to Xywav study. J Clin Sleep Med. 2024 Sep 1;20(9):1467-1477. doi: 10.5664/jcsm.11182.

Reference Type DERIVED
PMID: 38652499 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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JZP258-401

Identifier Type: -

Identifier Source: org_study_id

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