TAK-861 for Narcolepsy

Recruiting at 71 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Takeda

Must be taking: TAK-861

Must not be taking: Antidepressants, Anticonvulsants

Disqualifiers: Suicide risk, Liver issues, 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: 1

Duration: Up to 5 years

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called TAK-861 to determine its safety and tolerability in people with type 1 narcolepsy. Participants will receive one of two different doses of TAK-861 for up to five years. The trial targets individuals who have completed a previous study with TAK-861 and continue to experience narcolepsy-related sleep issues. As a Phase 2 and Phase 3 trial, it evaluates TAK-861's effectiveness in a larger group and represents the final step before FDA approval, offering participants an opportunity to advance narcolepsy treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who need to take certain medications for conditions like anxiety, depression, heart disease, or significant liver, lung, or kidney disease.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TAK-861 is generally safe and well-tolerated. In earlier trials, participants did not experience serious treatment-related side effects, indicating that most people did not encounter major problems with TAK-861. The treatment has been used to improve symptoms like excessive daytime sleepiness and cataplexy, a sudden loss of muscle control. Its testing in later stages of clinical trials suggests evidence of safety for humans. However, individual experiences can vary, so discussing any concerns with the trial team is important. ^{1 2 3 4 5}

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

Researchers are excited about TAK-861 for narcolepsy because it offers a novel approach in tackling this sleep disorder. Unlike standard treatments, which often include medications like modafinil or sodium oxybate that primarily boost wakefulness or regulate sleep cycles, TAK-861 targets a different pathway. This drug works by potentially modulating specific brain receptors linked to sleep regulation, offering an innovative mechanism of action. By focusing on these distinct pathways, TAK-861 could provide more effective and lasting relief from narcolepsy symptoms, setting it apart from current therapies.

What evidence suggests that TAK-861 might be an effective treatment for narcolepsy?

Research has shown that TAK-861 greatly helps people with narcolepsy type 1. Studies have found that TAK-861 improves alertness and reduces tiredness. Specifically, patients were better able to stay awake and had fewer episodes of sudden muscle weakness, known as cataplexy. Additionally, TAK-861 decreased brief, unintended sleep episodes, called microsleeps. These findings suggest that TAK-861 is a promising option for effectively managing narcolepsy symptoms. Participants in this trial will receive either TAK-861 Dose 1 or Dose 2 to further evaluate its effectiveness. ^{1 5 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for people with narcolepsy who have already taken TAK-861 in earlier studies without serious side effects. They shouldn't have other sleep disorders, major depression recently, digestive issues affecting drug absorption, seizures, significant heart or liver diseases, recent strokes or cancer within the last 5 years.

Inclusion Criteria

I have narcolepsy, finished a TAK-861 study, and my doctor agrees I can join.

Exclusion Criteria

Participant has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 times the upper limit of normal (ULN) at multiple visits in the parent study and the findings are of clinical significance, per investigator or sponsor opinion, or ALT/AST >1.5 times ULN during the screening period for participants with a dosing gap.

Participant has a positive urine screen for drugs of abuse (findings confirmed) and/or positive alcohol test during any visit in their prior TAK-861 study, or during the screening period for participants with a dosing gap.

I have had a stroke or mini-stroke in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAK-861 for up to approximately 5 years to evaluate safety and tolerability

Up to 5 years

Multiple visits (in-person and home health)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• TAK-861

Trial Overview The study tests the safety and tolerability of a drug called TAK-861 on individuals with type 1 and type 2 narcolepsy who participated in previous related trials. It aims to understand how well these patients can handle continued treatment.

How Is the Trial Designed?

Group I: TAK-861 Dose 2 Experimental Treatment 1 Intervention

Participants will receive TAK-861 dose 2 for up to approximately 5 years.

Group II: TAK-861 Dose 1 Experimental Treatment 1 Intervention

Participants will receive TAK-861 dose 1 for up to approximately 5 years.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Published Research Related to This Trial

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]

TAK-925 is a selective agonist for the orexin 2 receptor (OX2R) that effectively promotes wakefulness in mice, indicating its potential as a treatment for narcolepsy and related sleep disorders.

The compound was developed through optimization of an earlier discovery and shows promise due to its ability to penetrate the brain and enhance wakefulness during sleep phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist. Fujimoto, T., Rikimaru, K., Fukuda, K., et al.[2022]

The TAAR1 agonist RO5256390 significantly reduced rapid eye movement (REM) sleep and mitigated cataplexy in mouse models of narcolepsy, indicating its potential as a new treatment pathway for this disorder.

Both the full agonist RO5256390 and the partial agonist RO5263397 promoted wakefulness and reduced cataplexy episodes, suggesting that targeting TAAR1 could effectively address key symptoms of narcolepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trace Amine-Associated Receptor 1 Agonists as Narcolepsy Therapeutics. Black, SW., Schwartz, MD., Chen, TM., et al.[2018]

In a study using narcoleptic mice, two HCRTR2 agonists, TAK-925 and ARN-776, were found to significantly promote wakefulness and eliminate cataplexy, a common symptom of narcolepsy, especially at higher doses.

Both compounds increased gamma EEG activity and gross motor activity, indicating their potential as effective treatments for narcolepsy, although they did not cause a rebound in NREM sleep, suggesting a targeted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice. Sun, Y., Ranjan, A., Tisdale, R., et al.[2023]

Danavorexton (TAK-925) is a promising new treatment for narcolepsy type 1 (NT1) that activates orexin 2 receptors, showing potential to improve wakefulness and reduce sleep fragmentation in preclinical models.

In tests on mice with NT1, danavorexton not only promoted wakefulness but also helped control body weight gain, suggesting it may address multiple symptoms of the disorder effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Danavorexton, a selective orexin 2 receptor agonist, provides a symptomatic improvement in a narcolepsy mouse model. Ishikawa, T., Hara, H., Kawano, A., et al.[2022]

Citations

1. takeda.com takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/

Takeda Presents Orexin Data from Landmark Oveporexton ... Discover how Takeda's Oveporexton (TAK-861) Phase 3 studies reveal significant improvements in narcolepsy type 1 symptoms, marking a ...

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000208433

Efficacy and Safety of TAK-861, an Oral Orexin Receptor 2 ... Compared with placebo, improvements from baseline to week 8 were achieved with TAK-861 doses in SOL-MWT (LS means change 12.5–25.4 vs −1.2 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05687903

A Study of TAK-861 in Participants With Narcolepsy Type 1 This study will look at the effect of TAK-861 on improvement in narcolepsy symptoms, including excessive daytime sleepiness (EDS) and number of cataplexy ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40367374/

Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, ... In this phase 2 trial involving participants with narcolepsy type 1, oveporexton significantly improved measures of wakefulness, sleepiness, ...

5. neurologylive.com neurologylive.com/view/investigational-therapy-tak-861-reduces-microsleeps-phase-2-trial-nt1

Investigational Therapy TAK-861 Reduces Microsleeps in ... TAK-861 significantly reduced microsleep rates and delayed microsleep onset in NT1 patients, demonstrating its potential as an effective ...

6. takeda.com takeda.com/newsroom/newsreleases/2024/tak-861-data-at-sleep-2024-on-narcolepsy-type-1/

Takeda's TAK-861 Phase 2b Late-Breaking Data ... The dataset showed that TAK-861 was generally safe and well tolerated during the study, with no treatment-related serious treatment-emergent ...

7. nature.com nature.com/articles/s41598-024-70594-1

TAK-861, a potent, orally available orexin receptor 2 ... Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a ...

8. touchneurology.com touchneurology.com/insight/oveporexton-phase-3-narcolepsy-type-1-treatment/

Oveporexton phase 3 data signal new hope for narcolepsy ... Data presented at World Sleep 2025 from two global narcolepsy phase III trials, FirstLight (TAK‑861‑3001) (NCT06470828) and RadiantLight ...