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RecruitingNCT07625280XYRISEUpdated Oct 8, 2026

A Study Evaluating the Efficacy and Safety of Xywav Expanded Dosing vs Placebo in Participants With Narcolepsy or IH

A Phase 3 interventional study of Xywav and Placebo in Narcolepsy and Idiopathic Hypersomnia, sponsored by Jazz Pharmaceuticals. Recruiting at 15 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-10-08.

Sponsored by Jazz Pharmaceuticals · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Started Jul 2026; still recruiting 4 months later.
Updated Oct 8, 202612 sites addedGo to Updates ↓
Phase
Phase 3
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy and safety of expanded Xywav dosing regimens in adult participants with narcolepsy or idiopathic hypersomnia (IH).

Read the detailed description

The trial has 3 treatment periods: open label titration and optimization period (OL-TOP), stable dose period (SDP) and the double-blind randomized withdrawal period (DBRWP). Participants will be evaluated by their disease cohort (Narcolepsy and IH). Once eligibility to participate in the trial is confirmed, eligible participants will begin OL-TOP. Participants with narcolepsy and IH will be assigned to receive either a once-nightly expanded dosing of Xywav or a twice-nightly expanded dosing of Xywav. Assignment is dependent on participant's standard oxybate treatment and the treating investigator's decision. During OL-TOP, participants' Xywav dosing will be adjusted until they achieve a stable dose. This period can last up to 12 weeks. Once a stable dose is achieved, participants will begin the SDP. During the SDP, all participants will receive the stable Xywav dose for 2 additional weeks. Afterwards, the participants will begin the DBRWP. During this period, participants will be randomized to either continue on their stable dose of Xywav or receive placebo for 2 more weeks. In total, the participants will receive treatment in the trial for up to 16 weeks.

02

Conditions studied

  • Narcolepsy
  • Idiopathic Hypersomnia

Keywords

  • Xywav
  • Narcolepsy Type 1
  • NT1
  • Narcolepsy Type 2
  • NT2
  • IH
03

In context

Narcolepsy

157 studies on the registry are indexed under Narcolepsy; 37 are open to participants now.

This study's planned enrollment of 120 is above the median of 78 across 114 interventional studies indexed under Narcolepsy.

Browse Narcolepsy studies →

Lead sponsor

Jazz Pharmaceuticals is the lead sponsor of 173 studies on the registry; 18 are open to participants now.

Of its 42 completed or terminated interventional studies of FDA-regulated products, 32 (76%) have results posted.

Browse Jazz Pharmaceuticals studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Has a primary diagnosis of IH or narcolepsy Type 1 or Type 2 (NT1 or NT2)
  2. Participants with a primary diagnosis of NT1 must have a history of at least 14 cataplexy attacks in a typical 2-week period, based on participant history at the time of diagnosis and prior to initiating treatment.
  3. Participants with a primary diagnosis of IH must have an average total nightly sleep time of at least 7 hours, based on participant history at the time of diagnosis and prior to initiating treatment.
  4. If not currently treated with oxybate, has symptoms of excessive daytime sleepiness (EDS) with an Epworth Sleepiness Scale (ESS) score > 11 at screening and baseline.
  5. If currently treated with oxybate, must have documented improvement of EDS with oxybate treatment per the investigator's clinical judgement.
  6. If currently treated with oxybate, has been taking the same stable dosing regimen at a total nightly dosage of 3 g to 9 g (inclusive) for at least 2 months at screening.
  7. If previously treated with (and not currently taking) oxybate, must have been off oxybate treatment for at least 2 weeks prior to screening. Must not have previously discontinued oxybate due to reasons related to intolerability, safety, or lack of efficacy.
  8. If currently treated with alerting agents, has been taking the same dosage for at least 1 month prior to screening and has no current plans to adjust the dosage during the study period.
  9. If currently prescribed non-oxybate anticataplectic medications for cataplexy (NT1 only), must agree to taper off these medications (under the guidance and instruction of the investigator) during the OL-TOP and remain off these medications through the end of the DBRWP.
  10. If currently treated with nicotine replacement therapy, has been taking the same dosage for at least 1 month prior to screening and has no current plans to adjust the dosage during the study period.
  11. Adequate precautions

Exclusion criteria

Exclusion criteria:

  1. Shows evidence of a previous untreated or inadequately treated sleep disorder considered by the investigator to negatively impact the conduct of the study, including sleep-disordered breathing, parasomnias, circadian rhythm sleep disorders, or restless legs syndrome determined by a previous sleep-laboratory diagnosis or interview utilizing modules of the Diagnostic Interview for Sleep Patterns and Disorders.
  2. Has succinic semi-aldehyde dehydrogenase deficiency by medical history.
  3. Has uncontrolled hypothyroidism as determined by central clinical laboratory test results.
  4. Has a current seizure disorder.
  5. Has a history of head trauma associated with loss of consciousness in the past 5 years
  6. Has a history or presence of bipolar disorder, bipolar-related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders
  7. Has a history or presence of any unstable or medical condition, behavioral or psychiatric disorder, or history or presence of another neurologic 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.
  8. Has any other significant disease or disorder that, in the opinion of the investigator, may either put the participant, other participants, or study staff at risk because of participation in the study, may influence the result of the study, or may affect the participant's safety or ability to take part in the study.
  9. Any past or current medical conditions or experience that, in the investigator's clinical judgment, would preclude treatment with a once-nightly dose > 6 g up to 7.5 g dose or twice-nightly regimen with a total nightly dosage > 9 g up to 12 g (divided into 2 doses).
  10. Has any severe drug allergy or a history of allergic or severe adverse reactions or intolerance to Xyrem, Xywav, Gamma-hydroxybutyrate (GHB), or any components of the dosage forms.
  11. Has a history of substance abuse and/or a positive urine drug screen for drugs of abuse or alcohol

  12. Has recently taken, is taking, or plans to take any of the following:

    1. A substance or medication with Xywav use
    2. A medication with a known drug-drug interaction with Xywav
    3. Medications known to have clinically significant CNS sedating effects
    4. Other medications, natural health products, or substances from which the participant experiences clinically significant sedation
  13. Has recently taken, is taking, or plans to take an Orexin 2 receptor (OX2R) agonist during the study.
  14. Has tobacco-use disorder or uses vaping products that impact sleep
  15. Has excessive caffeine consumption that may impact sleep
  16. Has clinically significant abnormal laboratory values
  17. Has an occupation that requires nighttime or variable shift work
  18. Has plans for travel across more than 3 time zones during the study
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
120 participants (estimated)

Study arms

  • Active comparator
    Narcolepsy Cohort once-nightly expanded Xywav dose group

    Participants with narcolepsy will receive an expanded once-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will continue taking their stable dose of Xywav for 2 additional weeks.

    Drug: Xywav

  • Placebo comparator
    Narcolepsy Cohort once-nightly expanded Xywav followed by placebo group

    Participants with narcolepsy will receive an expanded once-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will take placebo for 2 additional weeks.

    Drug: Xywav · Other: Placebo

  • Active comparator
    Narcolepsy Cohort twice-nightly expanded Xywav dose group

    Participants with narcolepsy will receive an expanded twice-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will continue taking their stable dose of Xywav for 2 additional weeks.

    Drug: Xywav

  • Placebo comparator
    Narcolepsy Cohort twice-nightly expanded Xywav followed by placebo group

    Participants with narcolepsy will receive an expanded twice-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will take placebo for 2 additional weeks.

    Drug: Xywav · Other: Placebo

  • Active comparator
    IH Cohort once-nightly expanded Xywav dose group

    Participants with IH will receive an expanded once-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will continue taking their stable dose of Xywav for 2 additional weeks.

    Drug: Xywav

  • Placebo comparator
    IH Cohort once-nightly expanded Xywav followed by placebo group

    Participants with IH will receive an expanded once-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will take placebo for 2 additional weeks.

    Drug: Xywav · Other: Placebo

  • Active comparator
    IH Cohort twice-nightly expanded Xywav dose group

    Participants with IH will receive an expanded twice-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will continue taking their stable dose of Xywav for 2 additional weeks.

    Drug: Xywav

  • Placebo comparator
    IH Cohort twice-nightly expanded Xywav followed by placebo group

    Participants with IH will receive an expanded twice-nightly dosing of Xywav for up to 14 weeks until they reach a stable dose. Once stable dose is achieved, participants will take placebo for 2 additional weeks.

    Drug: Xywav · Other: Placebo

Interventions

  • DrugXywav

    0.5 g/ml calcium, magnesium, potassium, and sodium oxybates solution taken by mouth

    Also known as: JZP258

  • OtherPlacebo

    Placebo solution taken by mouth

06

What researchers measure

Primary outcomes

  1. Change in Epworth Sleepiness Scale (ESS) scores

    ESS is a self-administered questionnaire with 8 questions. Each question is scored on a scale ranging from 0 (would never fall asleep) to 3 (high chance of falling asleep). It has a total score ranging from 0 to 24, with a higher score representing increased daytime sleepiness.

    Time frame: End of Stable Dose Period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

Secondary outcomes

  1. Percentage of participants reporting minimally, much and very much worse in their CGIc questionnaire for IH or narcolepsy symptoms

    Clinical Global Impression of Change (CGIc) is a 7-point questionnaire completed by the treating physician that evaluates how the physician thinks the participant is responding to treatment since the end of stable dose period (up to week 14). Responses are graded from 1 (very much improved) to 7 (very much worse)

    Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  2. Percentage of participants reporting minimally, much and very much worse in their PGIc questionnaire for IH or narcolepsy symptoms

    Patient Global Impression of Change (PGIc) is a 7-point questionnaire completed by the participant evaluating how they think they are responding to treatment since the end of stable dose period (up to week 14). Responses are graded from 1 (very much improved) to 7 (very much worse)

    Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  3. Change in IHSS scores in participants with IH

    Idiopathic Hypersomnia Severity Scare (IHSS) is a 14-item self-reported questionnaire that assesses the severity and functional consequences of IH symptoms. Questions capture symptoms of excessive sleepiness, sleep inertia, and long sleep duration. The total score for the IHSS ranges from 0 to 50, with higher scores reflecting greater symptom severity.

    Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  4. Change in weekly rate of cataplexy (WRC) in participants with NT1

    WRC will be assessed for participants with NT1 using a cataplexy frequency electronic diary. Participants will be recording the number of daily cataplexy attacks experienced.

    Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  5. Percentage of participants reporting minimally, much and very much worse in their PGIc questionnaire for sleepiness

    Patient Global Impression of Change (PGIc) is a 7-point questionnaire completed by the participant evaluating how they think they are responding to treatment since the end of stable dose period (up to week 14). Responses are graded from 1 (very much improved) to 7 (very much worse)

    Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  6. Change in Clinical Global Impression of Severity (CGIs) Scores for Narcolepsy/IH symptoms

    CGIs is a 1 item question rated on a 5-point scale completed by the treating physician that evaluates how the physician thinks of the severity of the participant's IH/narcolepsy symptoms since the end of stable dose period (up to week 14). Responses are graded from 1 (normal) to 5 (amongst the most extremely ill patients).

    Time frame: End of stable dose visit period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  7. Change in Patient Global Impression of Severity (PGIs) Scores for Narcolepsy/IH symptoms

    PGIs is a 1 item question rated on a 5-point scale completed by the participant that evaluates how the participant thinks of the severity of their IH/narcolepsy symptoms since the end of stable dose period (up to week 14). Responses are graded from 1 (none/no symptoms) to 5 (very severe).

    Time frame: End of stable dose visit period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  8. Change in Patient Global Impression of Severity (PGIs) Scores for sleepiness

    PGIs is a 1 item question rated on a 5-point scale completed by the participant that evaluates how the participant thinks of the severity of their sleepiness since the end of stable dose period (up to week 14). Responses are graded from 1 (none/no sleepiness) to 5 (very severe).

    Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  9. Change in NSS scores in participants with NT1

    Narcolepsy Severity Scale (NSS) is a 15-item self-administered questionnaire that assesses the severity and consequences of the 5 major narcolepsy symptoms such as daytime sleepiness, cataplexy, hallucinations, sleep paralysis, and disrupted nighttime sleep. The total score for NSS ranges from 0 to 57, with the higher score indicating greater symptom severity

    Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  10. Change in NSS-2 scores in participants with NT2

    NSS-2 is a modified NSS self-administered questionnaire with only 12 items (omits questions regarding cataplexy). The total score for NSS-2 ranges from 0 to 44, with the higher score indicating greater symptom severity

    Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  11. Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to the end of the Safety follow up visit (Up to Week 18)

  12. Change in average total sleep time

    Average total sleep time over a 7-day period as per eDiary recordings

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  13. Change in average sleep latency

    Average time it takes a participant to fall asleep over a 7-day period as per eDiary recordings

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  14. Change in average wake after sleep onset (WASO)

    Average time (in minutes) the participant stays awake after they have fallen asleep over a 7-day period per eDiary recordings

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  15. Change in average number of awakenings after sleep onset (NAASO)

    Average number of nighttime wakings over a 7-day period as per their eDiary recordings

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  16. Sleep quality

    Sleep quality as described by participants across five response categories (Very poor, Poor, Fair, Good, Very good), with higher categories indicating better sleep quality evaluated at end of stable dose period (up to Week 14) and at end of DBRWP (up to Week 16)

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  17. Sleep episode frequency

    Participant-reported frequency of unintentionally falling asleep during the previous day. Response options are: 0 times, 1 time, 2 times, 3 times, and 4 or more times. Higher response categories indicate more frequent unintentional daytime sleep episodes quality evaluated at end of stable dose period (up to Week 14) and at end of DBRWP (up to Week 16).

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

  18. Difficulty maintaining wakefulness

    Participant-reported difficulty staying awake during low-stimulation activities. Response options are: Not at all, A little of the time, Some of the time, Most of the time, and All or almost all of the time quality evaluated at end of stable dose period (up to Week 14) and at end of DBRWP (up to Week 16).

    Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)

07

Study locations

15 of 15 sites recruiting
08

References and documents

Individual participant data

Plan to share: Yes — In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com.

Data sharing details ↗ · www.jazzpharma.com

No publications or documents are linked to this record.

09

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Jul 2026 (actual). Primary completion is estimated for Dec 2027, 17 months after the start.

Of 14 phase 3 interventional studies under Narcolepsy, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 40. This study's planned 17 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
May 27, 2026
First posted
Jun 4, 2026
StartActual
Jul 9, 2026
Primary completionEst.
Dec 23, 2027
CompletionEst.
Jan 6, 2028
Last update
Oct 8, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Sites
12 sites added
Show 12 added (12 United States)
  • Sleep Disorders Center of Alabama · Birmingham, United States
  • Amnova Clinical Research · Irvine, United States
  • Long Beach Research Institute · Long Beach, United States
  • Delta Waves Sleep Disorder and Research Center · Colorado Springs, United States
  • Flourish Research Miami · Miami, United States
  • Centricity Research Rincon - DBA IACT Health Southeast Lung Associates Research · Rincon, United States
  • Research Carolina Elite · Denver, United States
  • Science 37 · Morrisville, United States
  • K2 Medical Research Nashville · Nashville, United States
  • Future Search Trials - Austin Neurology · Austin, United States
  • FutureSearch Trials of Dallas · Dallas, United States
  • Tricoastal Narcolepsy and Sleep Disorders Center · Sugar Land, United States
Oct 8, 2026
Show all 1 update
  1. Oct 8, 2026
    12 sites added
    Show 12 added (12 United States)
    • Sleep Disorders Center of Alabama · Birmingham, United States
    • Amnova Clinical Research · Irvine, United States
    • Long Beach Research Institute · Long Beach, United States
    • Delta Waves Sleep Disorder and Research Center · Colorado Springs, United States
    • Flourish Research Miami · Miami, United States
    • Centricity Research Rincon - DBA IACT Health Southeast Lung Associates Research · Rincon, United States
    • Research Carolina Elite · Denver, United States
    • Science 37 · Morrisville, United States
    • K2 Medical Research Nashville · Nashville, United States
    • Future Search Trials - Austin Neurology · Austin, United States
    • FutureSearch Trials of Dallas · Dallas, United States
    • Tricoastal Narcolepsy and Sleep Disorders Center · Sugar Land, United States
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07625280
Lead sponsor
Jazz Pharmaceuticals
Collaborators
Jazz Pharmaceuticals Ireland Limited
Responsible party
Sponsor
First posted
Jun 4, 2026
Start date
Jul 9, 2026
Primary completion
Dec 23, 2027 (estimated)
Completion
Jan 6, 2028 (estimated)
Last update
Oct 8, 2026

Study contacts

Clinical Trial Disclosure & Transparency
Contact
ClinicalTrialDisclosure@JazzPharma.com
215-832-3750

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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