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

Narcolepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04794491
• Other study ID #: JZP258-401
• Status: Completed
• Phase: Phase 4
• Start date: March 22, 2021
• Est. completion date: November 15, 2022

Study information

• Verified date: January 2024
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: November 15, 2022
• Est. primary completion date: November 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Narcolepsy

Intervention

Drug:
• JZP-258
Maximum nightly dosage of 9 grams, administered once, twice or thrice nightly, with no single dose > 6 g

Locations

Country	Name	City	State
United States	Wright Clinical Research, LLC	Alabaster	Alabama
United States	FutureSearch Trials of Neurology	Austin	Texas
United States	Pulmonary Associates of the Southeast, PC	Birmingham	Alabama
United States	Sleep Disorders Center of Alabama	Birmingham	Alabama
United States	The Center for Sleep & Wake Disorders	Chevy Chase	Maryland
United States	Intrepid Research LLC	Cincinnati	Ohio
United States	Cleveland Clinic, Sleep Disorders Center	Cleveland	Ohio
United States	Delta Waves, Inc.	Colorado Springs	Colorado
United States	Bogan Sleep Consultants, LLC	Columbia	South Carolina
United States	Geisinger Clinic	Danville	Pennsylvania
United States	Ohio Sleep Medicine Institute	Dublin	Ohio
United States	Minnesota Lung Center	Edina	Minnesota
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	WMed Center for Clinical Research	Kalamazoo	Michigan
United States	Pulmonary Disease Specialists, PA d/b/a PDS Research	Kissimmee	Florida
United States	Santa Monica Clinical Trials	Los Angeles	California
United States	Southern California Institute For Respiratory Diseases, Inc.	Los Angeles	California
United States	Southern California Institute For Respiratory Diseases, Inc./ Tower Sleep Medicine	Los Angeles	California
United States	Sleep Practitioners LLC	Macon	Georgia
United States	Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences	North Charleston	South Carolina
United States	Stanford University- Sleep Medicine	Redwood City	California
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	Clayton Sleep Institute, LLC	Saint Louis	Missouri
United States	Sleep Therapy & Research Center	San Antonio	Texas
United States	SDS Clinical Trials, Inc	Santa Ana	California
United States	Clinical Research Institute	Stockbridge	Georgia
United States	Clinical Research of West Florida, Inc	Tampa	Florida
United States	Florida Pediatric Research Institute, LLC	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Characterization of Meals Relative to Dosing	Types of meals consumed before dosing.	Baseline to Week 8
Primary	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