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

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04794491
• Collaborator: (none)
• Enrollment: 100
• Locations: 28
• Arm: 1
• Anticipated Duration (Months): 16.8
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Narcolepsy	Drug: JZP-258	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 9, 2021
• Anticipated Primary Completion Date: Aug 1, 2022
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants Converted from Xyrem to XYWAV [Baseline to Week 8]

Secondary Outcome Measures

1. Change in Epworth Sleepiness Scale (ESS) [Baseline to Week 8]

   Changes in ESS scores between the Baseline period and ET or E/D, as applicable

2. Number of Participants with Participant Global Impression of Change (PGIc) Values [Week 8]

   PGIc values will be measured at the ET or E/D, as applicable. The number of participants with each response will be summarized.

3. Time to Achieve Optimized Dose and Regimen [Baseline to Week 8]

   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.

4. Number of Changes from the First Dose and Regimen to Optimized Dose and Regimen [Baseline to Week 8]

5. Number of Participants Dosing Fasted Versus Dosing Without Consideration of Food [Baseline to Week 8]

6. Duration of time between the last meal relative to dosing [Baseline to Week 8]

   The difference between the time of day that participants ate their last meal and the time of day participants take their first dose.

7. Characterization of Meals Relative to Dosing [Baseline to Week 8]

8. Change in Weekly Rate of Cataplexy Attacks [Baseline to Week 8]

9. Change in the Nausea Visual Analog Scale (NVAS) [Baseline to Week 8]

   Tolerability associated with Xyrem and XYWAV will be measured based on an NVAS assessment administered electronically.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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

1. 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:

9. Presence of clinically significant and untreated obstructive or central sleep apnea (as determined by the investigator or documented previously); or one of the following:

10. Apnea index (AI) >10 if on Obstructive Sleep Apnea (OSA) treatment or untreated, or

11. Clinically significant hypoventilation, or

12. 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.

13. 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.

14. Meet criteria for current major depression based on clinical interview

15. Have any clinically relevant medical, behavioral, or psychiatric disorder (other than narcolepsy) that is associated with excessive sleepiness

16. Have a history or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria

17. 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

18. Display relevant suicidality as indicated by Columbia Suicide Severity Rating Scale (C-SSRS) evaluation at screening

19. Display moderate to severe depression as indicated by the Participant Health Questionnaire - 9 (PHQ-9) at screening

20. Are a female participant who is pregnant or breastfeeding

Prior/Concomitant Therapy

1. 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

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wright Clinical Research, LLC	Alabaster	Alabama	United States	35007
2	Sleep Disorders Center of Alabama	Birmingham	Alabama	United States	35213
3	Pulmonary Associates of the Southeast, PC	Birmingham	Alabama	United States	35243
4	Santa Monica Clinical Trials	Los Angeles	California	United States	90025
5	Southern California Institute For Respiratory Diseases, Inc./ Tower Sleep Medicine	Los Angeles	California	United States	90048
6	Southern California Institute For Respiratory Diseases, Inc.	Los Angeles	California	United States	90048
7	Stanford University- Sleep Medicine	Redwood City	California	United States	94063
8	SDS Clinical Trials, Inc	Santa Ana	California	United States	92705
9	Delta Waves, Inc.	Colorado Springs	Colorado	United States	80918
10	Pulmonary Disease Specialists, PA d/b/a PDS Research	Kissimmee	Florida	United States	34741
11	Clinical Research of West Florida, Inc	Tampa	Florida	United States	33606
12	Florida Pediatric Research Institute, LLC	Winter Park	Florida	United States	32789
13	Sleep Practitioners LLC	Macon	Georgia	United States	31210
14	Clinical Research Institute	Stockbridge	Georgia	United States	30281
15	The Center for Sleep & Wake Disorders	Chevy Chase	Maryland	United States	20815
16	WMed Center for Clinical Research	Kalamazoo	Michigan	United States	49008
17	Minnesota Lung Center	Edina	Minnesota	United States	55435
18	Clayton Sleep Institute, LLC	Saint Louis	Missouri	United States	63123
19	Clinical Research of Gastonia	Gastonia	North Carolina	United States	28054
20	Intrepid Research LLC	Cincinnati	Ohio	United States	45245
21	Cleveland Clinic, Sleep Disorders Center	Cleveland	Ohio	United States	44195
22	Ohio Sleep Medicine Institute	Dublin	Ohio	United States	43017
23	Geisinger Clinic	Danville	Pennsylvania	United States	17822
24	Bogan Sleep Consultants, LLC	Columbia	South Carolina	United States	29201
25	Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences	North Charleston	South Carolina	United States	29425
26	Clinical Research of Rock Hill	Rock Hill	South Carolina	United States	29732
27	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
28	Sleep Therapy & Research Center	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Jazz Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04794491
• Other Study ID Numbers: JZP258-401
• First Posted: Mar 12, 2021
• Last Update Posted: Jul 25, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Narcolepsy

Study Results

No Results Posted as of Jul 25, 2022