An Interventional Safety Switch Study (Segue Study) of XYWAV in Narcolepsy
Condition: Narcolepsy
MeSH terms: Narcolepsy
Intervention: JZP-258
Intervention description: Maximum nightly dosage of 9 grams, administered once, twice or thrice nightly, with no single dose > 6 g
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.