JZP441 for Narcolepsy

Recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called JZP441 for people with narcolepsy type 1. Narcolepsy is a sleep disorder that makes it hard to stay awake during the day. Participants will receive either one of three different doses of JZP441 or a placebo (a substance with no active treatment). This trial might suit adults diagnosed with narcolepsy type 1 who experience excessive daytime sleepiness.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that JZP441 is likely to be safe for humans?

Research has shown that JZP441 has been tested on healthy individuals and may help them stay awake, as demonstrated in the Maintenance of Wakefulness Test. However, some side effects have been reported. In one study, some participants experienced vision problems, leading to the study's termination. While this provides some information, JZP441 remains in the early testing stages for treating narcolepsy type 1. Consequently, limited safety information exists for its use in narcolepsy. Early trials primarily focus on safety, so further research is needed to understand how well individuals can tolerate this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for narcolepsy?

Researchers are excited about JZP441 for narcolepsy because it could offer a new approach compared to current treatments like modafinil and sodium oxybate. Unlike these standard options that generally work by promoting wakefulness or adjusting neurotransmitter levels, JZP441 might target narcolepsy through a unique mechanism of action, though details are still emerging. This novel approach has the potential to address symptoms more effectively or with fewer side effects, sparking interest in its clinical development.

What evidence suggests that JZP441 might be an effective treatment for narcolepsy?

Research shows that JZP441 is being developed to help treat narcolepsy type 1 (NT1), a condition characterized by difficulty staying awake during the day. Although specific data on JZP441's effectiveness is limited, its development is based on a promising mechanism of action. Scientists believe it could help improve wakefulness. Earlier studies on similar treatments have demonstrated a reduction in symptoms such as excessive daytime sleepiness. Overall, JZP441 is in the early testing stages, and initial results suggest it might be a useful option for managing NT1 symptoms. ^{1 2 4 5 6}

Who Is on the Research Team?

Global Medical Lead

Principal Investigator

Jazz Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06961266

NCT06961266 | A Study to Investigate Efficacy, Safety ... 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 ...

2. withpower.com withpower.com/trial/phase-1-narcolepsy-3-2025-dca3e

JZP441 for Narcolepsy · Recruiting Participants for Phase ... 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 ...

3. labiotech.eu labiotech.eu/in-depth/new-narcolepsy-treatments/

New narcolepsy treatments: pipeline drugs to watch in 2025 Alixorexton was generally well tolerated at all doses tested, according to a press release. Improvements in other symptoms such as fatigue and ...

4. delveinsight.com delveinsight.com/blog/narcolepsy-treatment-landscape

Narcolepsy Treatment Heats Up with Promising Pipelines In July 2025, Takeda announced overwhelmingly positive results from two large Phase III trials, FirstLight and RadiantLight, where oveporexton ...

5. jazzpharma.com jazzpharma.com/science/pipeline

Pipeline The safety, tolerability, pharmacokinetics and pharmacodynamics of JZP441 are being investigated in narcolepsy Type 1 patients. JZP324. Narcolepsy. PHASE 1.

6. fiercebiotech.com fiercebiotech.com/biotech/jazz-halts-recently-licensed-sleep-disorder-med-after-clocking-visual-disturbances-and-cv

Jazz halts sleep disorder med trial over 'visual disturbances' Tan said that the drug, JZP441, demonstrated proof-of-concept in healthy volunteers as measured by the Maintenance of Wakefulness Test (MWT).