Low-Sodium Oxybate for Narcolepsy

Recruiting at57 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Waitlist Available

Sponsor: Jazz Pharmaceuticals

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new version of a narcolepsy medication with less salt. It aims to see if this change lowers blood pressure in people with narcolepsy who are currently using a high-sodium version. A lower sodium version of this medication is approved for treating excessive daytime sleepiness and cataplexy in patients with narcolepsy as young as seven years old.

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.

What data supports the idea that Low-Sodium Oxybate for Narcolepsy is an effective drug?

The available research shows that Low-Sodium Oxybate effectively improves symptoms of narcolepsy, such as cataplexy and excessive daytime sleepiness. In two major studies, people who took Low-Sodium Oxybate had better results than those who took a placebo, meaning they experienced fewer symptoms. Additionally, those who switched from Low-Sodium Oxybate to a placebo saw their symptoms worsen, indicating the drug's effectiveness. Compared to other treatments, Low-Sodium Oxybate is unique because it addresses both cataplexy and excessive daytime sleepiness, unlike some other drugs that only target one of these symptoms. ^{1 2 3 4 5}

What safety data is available for Low-Sodium Oxybate in treating narcolepsy?

The provided research does not contain specific safety data for Low-Sodium Oxybate or its related formulations (High-Sodium Oxybate, XYREM, Sodium oxybate, LUMRYZ, XYWAV, JZP-258, Calcium, magnesium, potassium, and sodium oxybates) in the treatment of narcolepsy. The studies focus on hypokalemic periodic paralysis, hypomagnesemia, and seizure models, which are unrelated to the safety profile of Low-Sodium Oxybate for narcolepsy. ^{6 7 8 9 10}

Is High-Sodium Oxybate a promising drug for narcolepsy?

Yes, High-Sodium Oxybate, also known as XYWAV, is considered a promising drug for treating narcolepsy. ^{6 7 9 11 12}

Research Team

Eligibility Criteria

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.

Treatment Details

Interventions

• High-Sodium Oxybate (Sodium Oxybate)
• XYWAV (Sodium Oxybate)

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.

Participant Groups

Group I: JZP258 Experimental Treatment 1 Intervention

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

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

Findings from Research

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]

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]

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]

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]

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]

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 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]

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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Implications of Oxybate Dosing Regimen for Sleep, Sleep Architecture, and Disrupted Nighttime Sleep in Patients with Narcolepsy: A Commentary. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Preferences for Attributes of Sodium Oxybate Treatment: A Discrete Choice Experiment in Patients with Narcolepsy. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Hypokalemic periodic paralysis with unusual responses to acetazolamide and sympathomimetics. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Treatment of hypokalemic periodic paralysis with topiramate. [2018]

8. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Symptomatic hypomagnesemia in children. [2015]

9. England pubmed.ncbi.nlm.nih.gov

Beneficial effects of bumetanide in a CaV1.1-R528H mouse model of hypokalaemic periodic paralysis. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Surface charge impact in low-magnesium model of seizure in rat hippocampus. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Divalent cation-responsive myotonia and muscle paralysis in skeletal muscle sodium channelopathy. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Muscle channelopathies: does the predicted channel gating pore offer new treatment insights for hypokalaemic periodic paralysis? [2021]