Low-Sodium Oxybate for Narcolepsy

No longer recruiting at 59 trial locations

Overseen By Clinical Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Jazz Pharmaceuticals

Must be taking: High-sodium oxybate

Disqualifiers: Unstable medical condition, Cardiovascular disease, Atrial fibrillation, Resistant hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how switching from high-sodium oxybate to a low-sodium version called XYWAV (calcium, magnesium, potassium, and sodium oxybates) affects blood pressure in individuals with narcolepsy. Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks. Participants must have used a high-sodium oxybate like XYREM for at least six weeks before the trial. They should also continue any prescribed medications that might affect blood pressure throughout the study. As a Phase 4 trial, this study involves an FDA-approved treatment, aiming to understand its benefits for a broader patient population.

Do I have to stop taking my current medications for the trial?

The trial does not require you to stop your current medications. If you're taking stimulants, alerting agents, or antihypertensive therapies, you must continue the same dose throughout the study.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. If you are on stimulants, alerting agents, or blood pressure medications, you must continue taking them at the same dose throughout the study.

What is the safety track record for these treatments?

Research has shown that XYWAV, a low-sodium medication, is already approved by the FDA to treat narcolepsy and idiopathic hypersomnia in adults, indicating its safety has been evaluated for these conditions. Studies have identified common side effects, including nausea, headache, dizziness, anxiety, trouble sleeping, reduced appetite, sweating, and vomiting, occurring in more than 5% of adults taking XYWAV for these conditions. The treatment's Phase 4 trial status indicates thorough study and general safety for its approved uses. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about XYWAV (JZP258) because it offers a low-sodium alternative to the traditional high-sodium oxybate treatments for narcolepsy. While most oxybate treatments help manage cataplexy and excessive daytime sleepiness, they often come with high sodium content, which can be a concern for those at risk of heart and kidney issues. XYWAV contains significantly less sodium, potentially making it a safer long-term option for patients with narcolepsy who need to manage their sodium intake more carefully.

What evidence suggests that XYWAV is effective for narcolepsy?

Research has shown that XYWAV, a low-sodium version of oxybate, effectively treats narcolepsy by reducing sudden muscle weakness (cataplexy) and excessive daytime sleepiness. Studies indicate that it is as safe as the high-sodium version but contains 92% less sodium, benefiting overall health. Recent studies also suggest that switching from high-sodium to low-sodium oxybate can help lower blood pressure in people with narcolepsy. These findings suggest that XYWAV could be a promising option for managing narcolepsy symptoms, especially for those concerned about sodium intake. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-70 with narcolepsy, currently treated with high-sodium oxybate and stable doses of any blood pressure or wakefulness medications for at least 6 weeks prior to the study. Participants must not be pregnant, breastfeeding, have unstable medical conditions, significant cardiovascular disease, or psychiatric disorders that could impact their safety or study results.

Inclusion Criteria

I have been taking 6 to 9 grams of high-sodium oxybate every night for at least 6 weeks.

I have been diagnosed with Type 1 or Type 2 narcolepsy.

I am not pregnant or breastfeeding and, if capable of childbearing, I am using effective birth control.

Exclusion Criteria

History or presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the participant or interfere with study assessments or the ability of the participant to complete the study based on the judgment of the investigator

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 to 9 grams per night of JZP258 (XYWAV) for 6 consecutive weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• High-Sodium Oxybate
• XYWAV

Trial Overview The trial is testing the effect on blood pressure when switching from high-sodium oxybate (XYREM) to a low-sodium version called XYWAV in people with narcolepsy. The goal is to see if reducing sodium intake through medication changes can improve blood pressure.

How Is the Trial Designed?

Group I: JZP258 Experimental Treatment 1 Intervention

Participants will receive 6 to 9 grams per night of JZP258 (XYWAV) for 6 consecutive weeks.

High-Sodium Oxybate is already approved in United States, European Union for the following indications:

Approved in United States as XYREM for:

• Cataplexy
• Excessive daytime sleepiness in narcolepsy

Approved in European Union as XYREM for:

• Cataplexy
• Excessive daytime sleepiness in narcolepsy

Who Is Running the Clinical Trial?

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

In a study examining seizure-like activity in a low magnesium model, it was found that removing magnesium while maintaining calcium levels led to recurrent seizures in 67% of brain slices, highlighting the critical role of magnesium in seizure prevention.

Calcium levels significantly influence seizure activity; increasing calcium concentration to 3 mM completely stopped seizure generation, suggesting that calcium and magnesium work together to modulate neuronal excitability and may have potential anti-seizure properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surface charge impact in low-magnesium model of seizure in rat hippocampus. Isaev, D., Ivanchick, G., Khmyz, V., et al.[2021]

Both once-nightly (SXB-ER) and twice-nightly (SXB) dosing regimens of oxybate significantly improve disrupted nighttime sleep (DNS) in narcolepsy patients, based on polysomnographic data from five clinical trials.

Despite differences in pharmacokinetic profiles, both dosing regimens lead to similar improvements in sleep quality, with SXB showing a greater positive impact on sleep architecture during the second half of the night.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary. Rosenberg, R., Braceras, R., Macfadden, W., et al.[2023]

In a study involving 75 adults with narcolepsy, participants overwhelmingly preferred once-nightly sodium oxybate (ON-SXB) over the traditional twice-nightly dosing, highlighting that dosing frequency is a crucial factor in treatment adherence and patient satisfaction.

The main reasons for this preference included the convenience of not having to wake up for a second dose, fewer side effects, and overall ease of administration, indicating that ON-SXB could improve the quality of life for individuals with narcolepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferences for Attributes of Sodium Oxybate Treatment: A Discrete Choice Experiment in Patients with Narcolepsy. Dubow, J., Avidan, AY., Corser, B., et al.[2022]

Lower-sodium oxybate (Xywav®) is effective in treating cataplexy and excessive daytime sleepiness in adults and children with narcolepsy, as well as idiopathic hypersomnia in adults, based on two phase 3 trials with a randomized-withdrawal design.

Participants who switched to placebo during the trials experienced significant worsening of their symptoms, highlighting the efficacy of lower-sodium oxybate, which also has a tolerability profile similar to that of sodium oxybate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium, Magnesium, Potassium and Sodium Oxybates (Xywav®) in Sleep Disorders: A Profile of Its Use. Heo, YA.[2022]

A family with five affected members showed symptoms resembling hypokalemic periodic paralysis (HPP), but with normal or only moderately reduced serum potassium levels during attacks, suggesting a possible variant of HPP.

Treatment with oral potassium supplements and triamterene improved symptoms, while acetazolamide worsened weakness, indicating that this family may respond differently to common HPP treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypokalemic periodic paralysis with unusual responses to acetazolamide and sympathomimetics. Vern, BA., Danon, MJ., Hanlon, K.[2019]

A patient with paramyotonia congenita due to a specific Nav1.4 mutation experienced worsening muscle symptoms linked to low magnesium and calcium levels, but showed significant improvement after magnesium treatment.

Computer simulations indicated that low levels of divalent cations like magnesium can exacerbate muscle symptoms by affecting sodium channel activation, suggesting that magnesium supplementation could be a potential therapeutic approach for managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Divalent cation-responsive myotonia and muscle paralysis in skeletal muscle sodium channelopathy. Mankodi, A., Grunseich, C., Skov, M., et al.[2019]

Hypokalaemic periodic paralysis (hypoPP) is caused by dysfunction in sodium or calcium channels, leading to severe muscle paralysis due to low serum potassium levels, and recent research has identified abnormal gating pore currents in mutant channels as a key factor in the disease's mechanism.

Acetazolamide, a carbonic anhydrase inhibitor used for over 40 years to treat hypoPP, has an unclear mechanism of action, but recent advances in understanding the molecular pathophysiology of hypoPP may help clarify how this treatment works and guide future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Muscle channelopathies: does the predicted channel gating pore offer new treatment insights for hypokalaemic periodic paralysis? Matthews, E., Hanna, MG.[2021]

Topiramate, an anti-epileptic drug with carbonic anhydrase inhibitory properties, was successfully used to treat 11-year-old twins with hypokalemic periodic paralysis (hypoPP), leading to a decrease in the severity of their muscle weakness attacks.

This case suggests that topiramate could be a promising treatment option for hypoPP, warranting further research into its efficacy and safety for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypokalemic periodic paralysis with topiramate. Fiore, DM., Strober, JB.[2018]

In a mouse model of hypokalaemic periodic paralysis caused by a calcium channel mutation, bumetanide was shown to protect against muscle weakness and loss of excitability due to low potassium levels, indicating its potential as a therapeutic option.

This study highlights the importance of the chloride gradient in muscle function and suggests that bumetanide could be effective for patients with hypokalaemic periodic paralysis linked to either sodium or calcium channel mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis. Wu, F., Mi, W., Cannon, SC.[2022]

In a study of 24 children with symptomatic hypomagnesemia, the most common causes were drug-induced renal magnesium wasting, particularly from medications like aminoglycosides and furosemide, leading to symptoms such as seizures and weakness.

Most cases of symptomatic hypomagnesemia were transient and improved with magnesium supplementation, with only a few requiring long-term treatment, indicating that timely intervention can effectively manage this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic hypomagnesemia in children. Tsau, YK., Tsai, WY., Lu, FL., et al.[2015]

Sodium oxybate (Xyrem) is the only FDA-approved treatment specifically for cataplexy in narcolepsy and has recently been approved for excessive daytime sleepiness associated with the condition.

Unlike traditional antidepressants and stimulants, sodium oxybate effectively addresses both cataplexy and daytime sleepiness with a lower risk of tolerance and side effects when used correctly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy. Scharf, MB.[2015]

Sodium oxybate (SXB) significantly reduces cataplexy attacks and daytime sleepiness in adults with narcolepsy-cataplexy, based on a systematic review of 6 randomized controlled trials involving various efficacy measures.

While SXB is effective, it is associated with a higher incidence of mild to moderate adverse events, such as nausea and dizziness, compared to placebo, indicating that while it is generally well tolerated, patients should be monitored for these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. Alshaikh, MK., Tricco, AC., Tashkandi, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7953213/

JZP-258) in a placebo-controlled, double-blind, randomized ... Efficacy of LXB for the treatment of cataplexy and excessive daytime sleepiness was demonstrated. The safety profile of LXB was consistent with SXB.

2. investor.jazzpharma.com investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-showcases-phase-4-data-demonstrating-xywavr

Jazz Pharmaceuticals Showcases Phase 4 Data ... Jazz Pharmaceuticals Showcases Phase 4 Data Demonstrating Xywav® (calcium, magnesium, potassium, and sodium oxybates) Oral Solution Treatment ...

3. prnewswire.com prnewswire.com/news-releases/jazz-pharmaceuticals-presents-late-breaking-phase-4-data-showcasing-xywav-calcium-magnesium-potassium-and-sodium-oxybates-oral-solution-treatment-outcomes-in-narcolepsy-at-sleep-2025-302476849.html

Jazz Pharmaceuticals Presents Late-Breaking Phase 4 ... First presentation of the Phase 4 XYLO switch study reports blood pressure reductions in patients with narcolepsy when switching from twice-nightly high- to ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33184650/

JZP-258) in a placebo-controlled, double-blind, ... Study objectives: Evaluate efficacy and safety of lower-sodium oxybate (LXB), a novel oxybate medication with 92% less sodium than sodium oxybate (SXB).

5. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.11182

Effectiveness and optimization of low-sodium oxybate in ... Effectiveness and optimization of low-sodium oxybate in participants with narcolepsy switching from a high-sodium oxybate: data from the Substitution of Equal ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/021196s036,212690s001s006lbl.pdf

XYWAV® (calcium, magnesium, potassium, and sodium ... common adverse reactions in adults with narcolepsy or IH (≥5%) were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, ...

7. xywav.com xywav.com/

XYWAV for Narcolepsy & Idiopathic Hypersomnia | XYWAV® Learn about an FDA-approved treatment for cataplexy and/or excessive daytime sleepiness in narcolepsy and for idiopathic hypersomnia (IH) in adults.

8. xywavhcp.com xywavhcp.com/

XYWAV Official Healthcare Provider (HCP) Site | XYWAV XYWAV is the first and only FDA-approved treatment for both narcolepsy and idiopathic hypersomnia1,2. XYWAV® (calcium, magnesium, potassium, and sodium oxybates) ...