Clinical trial NCT04794491: An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Narcolepsy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Weekly Rate of Cataplexy Attacks
timeFrame: Baseline to Week 8
Secondary outcomes:
Other outcomes:
measure: Change in the Nausea Visual Analog Scale (NVAS)
timeFrame: Baseline to Week 8
measure: Number of Participants With Patient Global Impression of Change (PGIc) Values
timeFrame: Week 8
measure: Change in Epworth Sleepiness Scale (ESS)
timeFrame: Baseline to Week 8
measure: Time to Achieve Optimized Dose and Regimen
timeFrame: Baseline to Week 8
measure: Number of Changes From the First Dose and Regimen to Optimized Dose and Regimen
timeFrame: Baseline to Week 8
measure: Number of Participants Dosing Fasted Versus Dosing Without Consideration of Food
timeFrame: Baseline to Week 8
measure: Duration of Time Between the Last Meal Relative to Dosing
timeFrame: Baseline to Week 8
measure: Characterization of Meals Relative to Dosing
timeFrame: Baseline to Week 8
Locations:
city: Alabaster
country: United States
facility: Wright Clinical Research, LLC
state: Alabama
city: Birmingham
country: United States
facility: Sleep Disorders Center of Alabama
state: Alabama
city: Birmingham
country: United States
facility: Pulmonary Associates of the Southeast, PC
state: Alabama
city: Los Angeles
country: United States
facility: Santa Monica Clinical Trials
state: California
city: Los Angeles
country: United States
facility: Southern California Institute For Respiratory Diseases, Inc./ Tower Sleep Medicine
state: California
city: Los Angeles
country: United States
facility: Southern California Institute For Respiratory Diseases, Inc.
state: California
city: Redwood City
country: United States
facility: Stanford University- Sleep Medicine
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials, Inc
state: California
city: Colorado Springs
country: United States
facility: Delta Waves, Inc.
state: Colorado
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists, PA d/b/a PDS Research
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc
state: Florida
city: Winter Park
country: United States
facility: Florida Pediatric Research Institute, LLC
state: Florida
city: Macon
country: United States
facility: Sleep Practitioners LLC
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Institute
state: Georgia
city: Chevy Chase
country: United States
facility: The Center for Sleep & Wake Disorders
state: Maryland
city: Kalamazoo
country: United States
facility: WMed Center for Clinical Research
state: Michigan
city: Edina
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Saint Louis
country: United States
facility: Clayton Sleep Institute, LLC
state: Missouri
city: Gastonia
country: United States
facility: Clinical Research of Gastonia
state: North Carolina
city: Cincinnati
country: United States
facility: Intrepid Research LLC
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, Sleep Disorders Center
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine Institute
state: Ohio
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Columbia
country: United States
facility: Bogan Sleep Consultants, LLC
state: South Carolina
city: North Charleston
country: United States
facility: Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences
state: South Carolina
city: Rock Hill
country: United States
facility: Clinical Research of Rock Hill
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: San Antonio
country: United States
facility: Sleep Therapy & Research Center
state: Texas
Study officials:
References: