JZP441 for Narcolepsy

Recruiting at 4 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Jazz Pharmaceuticals

Must not be taking: Sodium oxybate, Pitolisant

Disqualifiers: Cardiac issues, Hypertension, Depression, others

Compensation: Varies

Number of Visits: Unknown

Duration: 11 weeks

8 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using any medications that could affect the evaluation of excessive daytime sleepiness (EDS) within a time period prior to the Baseline Visit corresponding to at least 5 half-lives of the drug(s). Additionally, you cannot use certain medications like XYWAV, high sodium oxybate, or pitolisant during the study.

What data supports the effectiveness of the drug JZP441 for narcolepsy?

Research on a similar drug, JZP-110, shows it helps people with narcolepsy stay awake and reduce excessive sleepiness by affecting certain brain chemicals. This suggests that JZP441 might also be effective for these symptoms. ^{1 2 3 4 5}

Is JZP441 safe for humans?

JZP441, also known as solriamfetol, has been studied for safety in people with narcolepsy. It is a wake-promoting drug that affects certain brain chemicals, and studies have evaluated its safety and effectiveness in treating excessive sleepiness. ^{1 3 6 7 8}

How does the drug JZP441 differ from other narcolepsy treatments?

JZP441 is unique because it acts as a wake-promoting agent by affecting both dopamine and norepinephrine, which are chemicals in the brain that help regulate wakefulness and alertness. This dual action may offer a different approach compared to other treatments that typically focus on just one of these pathways. ^{1 3 4 9 10}

What is the purpose of this trial?

Narcolepsy is a sleep disorder in which patients are not able to maintain wakefulness or require treatment to maintain wakefulness during the daytime. Narcolepsy is a lifelong neurologic disease for which no cure has been clinically available. JZP441 is currently being developed for the treatment of narcolepsy type 1 (NT1). This study will assess the safety of efficacy of JZP441 in adult patients with NT1.

Research Team

Global Medical Lead

Principal Investigator

Jazz Pharmaceuticals

Eligibility Criteria

This trial is for adults with narcolepsy type 1, a sleep disorder causing difficulty staying awake during the day. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to follow specific protocols.

Inclusion Criteria

Participant has an average sleep latency of less than 15 minutes as documented by the mean of the first 4 trials of the Baseline MWT, as determined by central assessment

I have been diagnosed with narcolepsy type 1 by a doctor.

I weigh at least 50 kg if male, 45 kg if female, and my BMI is between 18.0 and 35.0.

Exclusion Criteria

Current or history of psychotic or bipolar disorders

History or presence of substance use disorder, alcohol use disorder, or increased seizure risk

Presence of cardiodynamic abnormalities as defined by triplicate 12-lead ECG

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JZP441 or placebo in a 4-way crossover design to evaluate efficacy, safety, tolerability, and pharmacokinetics

11 weeks

Multiple visits for dose administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JZP441

Trial Overview The study is testing JZP441 against a placebo to see if it's safe and effective in treating narcolepsy type 1. Participants will randomly receive either the actual drug or a placebo without knowing which one they're getting.

Participant Groups

Group I: JZP441 Dose Level 3 Experimental Treatment 1 Intervention

Participants with narcolepsy type 1 who are randomized to receive JZP441.

Group II: JZP441 Dose Level 2 Experimental Treatment 1 Intervention

Participants with narcolepsy type 1 who are randomized to receive JZP441.

Group III: JZP441 Dose Level 1 Experimental Treatment 1 Intervention

Participants with narcolepsy type 1 who are randomized to receive JZP441.

Group IV: Placebo Placebo Group 1 Intervention

Participants with narcolepsy type 1 who are randomized to receive matching placebo.

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

Jazz Pharmaceuticals Ireland Limited

Industry Sponsor

Trials

2

Recruited

250+

Findings from Research

In a phase 2b trial involving 93 adults with narcolepsy, JZP-110 significantly improved wakefulness and reduced excessive sleepiness compared to placebo, with notable increases in sleep latency and patient-reported outcomes over 12 weeks.

JZP-110 was well tolerated at doses of 150-300 mg/day, although some patients experienced side effects like insomnia and headache, leading to a 6.8% discontinuation rate due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study. Ruoff, C., Swick, TJ., Doekel, R., et al.[2019]

Narcolepsy affects a small percentage of the population and is linked to genetic factors and the loss of hypocretin-producing neurons, suggesting an autoimmune component that may be triggered by environmental factors.

Current treatments like sodium oxybate and modafinil effectively manage symptoms such as excessive daytime sleepiness and cataplexy, while emerging therapies focus on both non-hypocretin-based and hypocretin-based approaches to improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of narcolepsy. Abad, VC., Guilleminault, C.[2020]

In a long-term study involving 201 participants with narcolepsy and cataplexy, low-sodium oxybate (LXB) demonstrated a safety profile similar to that of sodium oxybate (SXB), with common treatment-emergent adverse events (TEAEs) like headache, nausea, and dizziness occurring mostly early in treatment and generally lasting a short duration.

The prevalence of TEAEs decreased over the course of the 24-week open-label extension, indicating that LXB is well-tolerated over time, with headache being the most frequently reported adverse event during both the main study and the extension period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Tolerability During a Clinical Trial and Open-Label Extension of Low-Sodium Oxybate in Participants with Narcolepsy with Cataplexy. Bogan, RK., Foldvary-Schaefer, N., Skowronski, R., et al.[2023]

The study analyzed 17 randomized controlled trials involving five approved wake-promoting agents for narcolepsy, finding that all treatments were effective compared to placebo, with solriamfetol showing the greatest improvement in wakefulness and overall patient-reported outcomes.

Lower-sodium oxybate (LXB) demonstrated the best safety profile, with the lowest risk of adverse events, making it a promising option for narcolepsy treatment alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy and Safety of Multiple Wake-Promoting Agents for the Treatment of Excessive Daytime Sleepiness in Narcolepsy: A Network Meta-Analysis. Zhan, S., Ye, H., Li, N., et al.[2023]

Narcolepsy is primarily caused by the loss of neurons that produce hypocretin, a neuropeptide crucial for regulating wakefulness, with about 90% of patients with cataplexy being deficient in this substance.

Current treatments include stimulants and newer medications like modafinil and sodium oxybate, but the development of hypocretin receptor agonists holds promise for future therapies specifically targeting hypocretin deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. Zeitzer, JM., Nishino, S., Mignot, E.[2015]

References

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

Effect of Oral JZP-110 (ADX-N05) on Wakefulness and Sleepiness in Adults with Narcolepsy: A Phase 2b Study. [2019]

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

Efficacy of once-nightly sodium oxybate (FT218) in narcolepsy type 1 and type 2: post hoc analysis from the Phase 3 REST-ON Trial. [2023]

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

A randomized study of solriamfetol for excessive sleepiness in narcolepsy. [2020]

4. France pubmed.ncbi.nlm.nih.gov

[Narcolepsy, from Westphal to hypocretin]. [2019]

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

New developments in the management of narcolepsy. [2020]

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

Long-Term Safety and Tolerability During a Clinical Trial and Open-Label Extension of Low-Sodium Oxybate in Participants with Narcolepsy with Cataplexy. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Rare Case of Late-Onset Narcolepsy Type 1. [2020]

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

Comparative Efficacy and Safety of Multiple Wake-Promoting Agents for the Treatment of Excessive Daytime Sleepiness in Narcolepsy: A Network Meta-Analysis. [2023]

9. France pubmed.ncbi.nlm.nih.gov

[Narcolepsy with cataplexy]. [2015]

10. England pubmed.ncbi.nlm.nih.gov

The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. [2015]