NarcolepsyPhase 3XYRISENCT07625280
A Study Evaluating the Efficacy and Safety of Xywav Expanded Dosing vs Placebo in Participants With Narcolepsy or IH
A Phase 3 study testing Xywav in people with Narcolepsy and Idiopathic Hypersomnia, run by Jazz Pharmaceuticals at 15 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Narcolepsy, Idiopathic Hypersomnia
- What is being tested?
- Xywav
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 15 sitesUnited States
- Study dates
- 9 Jul 2026to 6 Jan 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a primary diagnosis of IH or narcolepsy Type 1 or Type 2 (NT1 or NT2)
- 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.
- 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.
- If not currently treated with oxybate, has clinically significant symptoms of excessive daytime sleepiness (EDS) with an Epworth Sleepiness Scale (ESS) score > 11 at screening and baseline.
- If currently treated with oxybate, must have documented improvement of EDS with oxybate treatment per the investigator's clinical judgement.
- 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.
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- 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.
- 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.
- 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.
- 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.
- Adequate contraceptive precautions
Who cannot join
- 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.
- Has succinic semi-aldehyde dehydrogenase deficiency by medical history.
- Has uncontrolled hypothyroidism as determined by central clinical laboratory test results.
- Has a current seizure disorder.
- Has a history of head trauma associated with loss of consciousness in the past 5 years
- Has a history or presence of bipolar disorder, bipolar-related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders
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- Has a history or presence of any unstable or clinically significant 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.
- 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.
- 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).
- 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.
- Has a history of substance abuse and/or a positive urine drug screen for drugs of abuse or alcohol
- Has recently taken, is taking, or plans to take any of the following:
- A substance or medication contraindicated with Xywav use
- A medication with a known drug-drug interaction with Xywav
- Medications known to have clinically significant CNS sedating effects
- Other medications, natural health products, or substances from which the participant experiences clinically significant sedation
- Has recently taken, is taking, or plans to take an Orexin 2 receptor (OX2R) agonist during the study.
- Has tobacco-use disorder or uses vaping products that impact sleep
- Has excessive caffeine consumption that may impact sleep
- Has clinically significant abnormal laboratory values
- Has an occupation that requires nighttime or variable shift work
- Has plans for travel across more than 3 time zones during the study
Trial locations and contacts
15 sites in 1 country. Contact the study team or a site near you to ask about taking part.
15 sites in 1 country
United States15 sites, 15 recruiting
- Recruiting
Future Search Trials - Austin Neurology
Austin, Texas, 78731
- Recruiting
Sleep Disorders Center of Alabama
Birmingham, Alabama, 35213
- Recruiting
Intrepid Research
Cincinnati, Ohio, 45245
- Recruiting
Delta Waves Sleep Disorder and Research Center
Colorado Springs, Colorado, 80918
- Recruiting
FutureSearch Trials of Dallas
Dallas, Texas, 75251
- Recruiting
Research Carolina Elite
Denver, North Carolina, 28037
- Recruiting
Ohio Sleep Medicine and Neuroscience Institute
Dublin, Ohio, 43017
- Recruiting
Amnova Clinical Research
Irvine, California, 92604
- Recruiting
Long Beach Research Institute
Long Beach, California, 90805
- Recruiting
Santa Monica Clinical Trials
Los Angeles, California, 90025
- Recruiting
Flourish Research Miami
Miami, Florida, 33135
- Recruiting
Science 37
Morrisville, North Carolina, 27560
- Recruiting
K2 Medical Research Nashville
Nashville, Tennessee, 37204
- Recruiting
Centricity Research Rincon - DBA IACT Health Southeast Lung Associates Research
Rincon, Georgia, 31326
- Recruiting
Tricoastal Narcolepsy and Sleep Disorders Center
Sugar Land, Texas, 77478
About this study
Official title: A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized-withdrawal Study to Evaluate the Efficacy and Safety of Expanded Dosing Regimens for Xywav in Adult Participants With Narcolepsy or Idiopathic Hypersomnia
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.
- Conditions
- Narcolepsy, Idiopathic Hypersomnia
- Being tested
- Xywav, Placebo
- Keywords
- Xywav, Narcolepsy Type 1, NT1, Narcolepsy Type 2, NT2, IH
- Medical subject headings
- Narcolepsy, Idiopathic Hypersomnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XywavDrug
Also called JZP258
0.5 g/ml calcium, magnesium, potassium, and sodium oxybates solution taken by mouth
PlaceboOther
Placebo solution taken by mouth
| Study group | Role | What they receive |
|---|---|---|
| Narcolepsy Cohort once-nightly expanded Xywav dose group | Active comparator | 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. Receives: Drug: Xywav |
| Narcolepsy Cohort once-nightly expanded Xywav followed by placebo group | Placebo comparator | 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. Receives: Drug: Xywav; Other: Placebo |
| Narcolepsy Cohort twice-nightly expanded Xywav dose group | Active comparator | 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. Receives: Drug: Xywav |
| Narcolepsy Cohort twice-nightly expanded Xywav followed by placebo group | Placebo comparator | 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. Receives: Drug: Xywav; Other: Placebo |
| IH Cohort once-nightly expanded Xywav dose group | Active comparator | 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. Receives: Drug: Xywav |
| IH Cohort once-nightly expanded Xywav followed by placebo group | Placebo comparator | 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. Receives: Drug: Xywav; Other: Placebo |
| IH Cohort twice-nightly expanded Xywav dose group | Active comparator | 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. Receives: Drug: Xywav |
| IH Cohort twice-nightly expanded Xywav followed by placebo group | Placebo comparator | 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. Receives: Drug: Xywav; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of Stable Dose Period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Secondary outcomes (18)
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)
Measured: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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)
Measured: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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.
Measured: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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.
Measured: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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)
Measured: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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).
Measured: End of stable dose visit period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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).
Measured: End of stable dose visit period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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).
Measured: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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
Measured: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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
Measured: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
Measured: Up to the end of the Safety follow up visit (Up to Week 18)
Change in average total sleep time
Average total sleep time over a 7-day period as per eDiary recordings
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in average sleep latency
Average time it takes a participant to fall asleep over a 7-day period as per eDiary recordings
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 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)
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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).
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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).
Measured: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2026
- Study start9 Jul 2026
- Primary completion23 Dec 2027 (estimated)
- Study completion6 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NarcolepsyStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Jazz Pharmaceuticals Ireland Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07625280
- Sponsor's protocol ID
- JZP258-304
- Acronym
- XYRISE
- Status last verified
- Oct 2026
- First submitted
- 27 May 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Double-blind, Placebo-controlled, Randomized-withdrawal Study to Evaluate the Efficacy and Safety of Expanded Dosing Regimens for Xywav in Adult Participants With Narcolepsy or Idiopathic Hypersomnia
- ClinicalTrials.gov ID
- NCT07625280
- Acronym / sponsor ID
- XYRISE / JZP258-304
- Conditions
- Narcolepsy, Idiopathic Hypersomnia
- Keywords
- Xywav, Narcolepsy Type 1, NT1, Narcolepsy Type 2, NT2, IH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Jazz Pharmaceuticals Ireland Limited
- Study start
- 9 Jul 2026 (actual)
- Primary completion
- 23 Dec 2027 (estimated)
- Study completion
- 6 Jan 2028 (estimated)
- First posted
- 4 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Narcolepsy Cohort once-nightly expanded Xywav dose group | Active comparator | Drug: XywavParticipants 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. |
| Narcolepsy Cohort once-nightly expanded Xywav followed by placebo group | Placebo comparator | Drug: Xywav, Other: PlaceboParticipants 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. |
| Narcolepsy Cohort twice-nightly expanded Xywav dose group | Active comparator | Drug: XywavParticipants 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. |
| Narcolepsy Cohort twice-nightly expanded Xywav followed by placebo group | Placebo comparator | Drug: Xywav, Other: PlaceboParticipants 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. |
| IH Cohort once-nightly expanded Xywav dose group | Active comparator | Drug: XywavParticipants 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. |
| IH Cohort once-nightly expanded Xywav followed by placebo group | Placebo comparator | Drug: Xywav, Other: PlaceboParticipants 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. |
| IH Cohort twice-nightly expanded Xywav dose group | Active comparator | Drug: XywavParticipants 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. |
| IH Cohort twice-nightly expanded Xywav followed by placebo group | Placebo comparator | Drug: Xywav, Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Has a primary diagnosis of IH or narcolepsy Type 1 or Type 2 (NT1 or NT2)
- 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.
- 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.
- If not currently treated with oxybate, has clinically significant symptoms of excessive daytime sleepiness (EDS) with an Epworth Sleepiness Scale (ESS) score > 11 at screening and baseline.
- If currently treated with oxybate, must have documented improvement of EDS with oxybate treatment per the investigator's clinical judgement.
Key exclusion criteria (22 listed)
- 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.
- Has succinic semi-aldehyde dehydrogenase deficiency by medical history.
- Has uncontrolled hypothyroidism as determined by central clinical laboratory test results.
- Has a current seizure disorder.
- Has a history of head trauma associated with loss of consciousness in the past 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XywavAlso: JZP2580.5 g/ml calcium, magnesium, potassium, and sodium oxybates solution taken by mouth | Drug | IH Cohort once-nightly expanded Xywav dose group, IH Cohort once-nightly expanded Xywav followed by placebo group, IH Cohort twice-nightly expanded Xywav dose group, IH Cohort twice-nightly expanded Xywav followed by placebo group, Narcolepsy Cohort once-nightly expanded Xywav dose group, Narcolepsy Cohort once-nightly expanded Xywav followed by placebo group, Narcolepsy Cohort twice-nightly expanded Xywav dose group, Narcolepsy Cohort twice-nightly expanded Xywav followed by placebo group |
| PlaceboPlacebo solution taken by mouth | Other | IH Cohort once-nightly expanded Xywav followed by placebo group, IH Cohort twice-nightly expanded Xywav followed by placebo group, Narcolepsy Cohort once-nightly expanded Xywav followed by placebo group, Narcolepsy Cohort twice-nightly expanded Xywav followed by placebo group |
Primary outcome
Change in Epworth Sleepiness Scale (ESS) scores
Time frame: End of Stable Dose Period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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.
18 secondary outcomes
Percentage of participants reporting minimally, much and very much worse in their CGIc questionnaire for IH or narcolepsy symptoms
Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Percentage of participants reporting minimally, much and very much worse in their PGIc questionnaire for IH or narcolepsy symptoms
Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in IHSS scores in participants with IH
Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in weekly rate of cataplexy (WRC) in participants with NT1
Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Percentage of participants reporting minimally, much and very much worse in their PGIc questionnaire for sleepiness
Time frame: At the end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in Clinical Global Impression of Severity (CGIs) Scores for Narcolepsy/IH symptoms
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)
Change in Patient Global Impression of Severity (PGIs) Scores for Narcolepsy/IH symptoms
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)
Change in Patient Global Impression of Severity (PGIs) Scores for 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)
Change in NSS scores in participants with NT1
Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in NSS-2 scores in participants with NT2
Time frame: End of stable dose period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)
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)
Change in average total sleep time
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in average sleep latency
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in average wake after sleep onset (WASO)
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Change in average number of awakenings after sleep onset (NAASO)
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Sleep quality
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Sleep episode frequency
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Difficulty maintaining wakefulness
Time frame: End of stable dose period (up to Week 14), End of Double-Blind Randomized-Withdrawal Period (up to Week 16)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Xywav in people with Narcolepsy and Idiopathic Hypersomnia, run by Jazz Pharmaceuticals at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trial Disclosure & Transparency (215-832-3750, ClinicalTrialDisclosure@JazzPharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Epworth Sleepiness Scale (ESS) scores (time frame: End of Stable Dose Period (up to Week 14), up to end of Double-Blind Randomized-Withdrawal Period (up to Week 16)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.