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

NCT07625280 | Recruiting Phase 3 FDA Drug

• 1 other identifier: JZP258-304
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Narcolepsy; Idiopathic Hypersomnia

Keywords

Xywav; Narcolepsy Type 1; NT1; Narcolepsy Type 2; NT2; IH

Outcome Measures

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.

  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

  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

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

• Change in IHSS scores in participants with IH

  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

  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

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

Study Arms (8)

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.

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.

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.

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.

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.

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.

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.

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.

Drug: Xywav; Other: Placebo

Interventions

Xywav DRUG

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

Also known as: JZP258

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

Placebo OTHER

Placebo solution taken by mouth

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• Jazz Pharmaceuticals Ireland Limited: collaborator

Study Sites (3)

Santa Monica Clinical Trials

Los Angeles, California, 90025, United States

RECRUITING

Intrepid Research

Cincinnati, Ohio, 45245, United States

RECRUITING

Ohio Sleep Medicine and Neuroscience Institute

Dublin, Ohio, 43017, United States

RECRUITING

MeSH Terms

Conditions

Narcolepsy; Idiopathic Hypersomnia

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Central Study Contacts

Clinical Trial Disclosure & Transparency

CONTACT

215-832-3750; ClinicalTrialDisclosure@JazzPharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2026
• First Posted: June 4, 2026
• Study Start: July 9, 2026
• Primary Completion (Estimated): December 23, 2027
• Study Completion (Estimated): January 6, 2028
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

US (3)