TAK-861 for Narcolepsy

No longer recruiting at 72 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Disqualifiers: Hepatic disease, Thyroid disease, Cancer, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, TAK-861, to evaluate its effectiveness in reducing narcolepsy symptoms, such as excessive daytime sleepiness and sudden muscle weakness (cataplexy). Participants will receive either TAK-861 or a placebo (a dummy treatment with no active drug) for 8 to 12 weeks, with an option for continued treatment in a separate study. The trial seeks individuals diagnosed with narcolepsy type 1 who regularly experience these symptoms. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that TAK-861 is generally safe for people. One study found that TAK-861 helped reduce symptoms such as excessive daytime sleepiness and sudden muscle weakness (cataplexy) in individuals with narcolepsy. Importantly, the study confirmed its safety.

Another study discovered that TAK-861 works by affecting orexin receptors, which help regulate sleep and wakefulness. This study also reported no serious side effects among participants.

The current trial is in an early stage, indicating that TAK-861 has demonstrated sufficient safety to be tested in more people. Overall, results so far suggest that TAK-861 is safe, but ongoing trials will provide more information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for narcolepsy, which often include stimulants like modafinil and amphetamines to manage symptoms, TAK-861 offers a unique approach. TAK-861 targets the orexin system, a different mechanism that plays a key role in regulating wakefulness and sleep balance. Researchers are excited about TAK-861 because it could offer a more targeted treatment with potentially fewer side effects compared to traditional options, which often come with concerns about dependency and cardiovascular effects. Additionally, the variety of dosages being tested, such as 0.5 mg BID up to 7 mg QD, provides flexibility to optimize effectiveness and minimize side effects for different patients.

What evidence suggests that this trial's treatments could be effective for narcolepsy?

Research shows that TAK-861, which participants in this trial may receive, has promising results for treating narcolepsy symptoms. Studies found that TAK-861 significantly improved alertness and reduced excessive daytime sleepiness. Participants taking TAK-861 also took longer to fall asleep during the day, meaning they stayed awake longer. Compared to a placebo, another treatment arm in this trial, those on TAK-861 reported feeling less sleepy and experienced fewer episodes of sudden muscle weakness, known as cataplexy. These findings suggest that TAK-861 could effectively manage narcolepsy symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults aged 18-70 with narcolepsy type 1 confirmed by sleep tests, a BMI of 18-40 kg/m^2, and specific genetic markers or low levels of the brain hormone orexin. Excluded are those with significant medical conditions like heart disease, liver or thyroid issues, history of cancer within five years (except certain skin cancers), head trauma, seizures, stroke risks, infectious diseases like hepatitis B/C or HIV, poor kidney function or high liver enzyme levels.

Inclusion Criteria

Your body mass index (BMI) is between 18 and 40.

You have been diagnosed with narcolepsy type 1 within the last 10 years using specific sleep tests.

You have a specific genetic marker or low levels of a substance in your spinal fluid related to a sleep disorder.

Exclusion Criteria

You have a significant heart condition such as heart disease, heart attack history, severe chest pain, abnormal heart rhythm, or heart failure.

The participant has medically significant hepatic or thyroid disease.

The participant has a clinically significant history of head injury or head trauma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAK-861 or placebo for 8 or 12 weeks to evaluate efficacy, safety, and tolerability

8-12 weeks

Multiple visits to the clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment, with 2 final visits 7 and 28 days after last dose

4 weeks

2 visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment with TAK-861 long-term

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• TAK-861

Trial Overview

The study is testing TAK-861 to see if it improves daytime sleepiness and cataplexy in people with narcolepsy. Participants will randomly receive either TAK-861 or a placebo for up to 12 weeks across various regions globally. Afterward, they may join an extension study where everyone gets TAK-861.

How Is the Trial Designed?

Group I: TAK-861 7 mg QD Experimental Treatment 2 Interventions

Participants received TAK-861 7 mg, orally, once daily (QD), from Day 1 to 56. Placebo was given as the second dose.

Group II: TAK-861 2 mg and 5 mg Experimental Treatment 1 Intervention

Participants received TAK-861 2 mg followed by 5 mg dose, orally, BID, from Days 1 to 56.

Group III: TAK-861 2 mg BID Experimental Treatment 1 Intervention

Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56.

Group IV: TAK-861 0.5 mg BID Experimental Treatment 1 Intervention

Participants received TAK-861 0.5 milligrams (mg), orally, BID, from Days 1 to 56.

Group V: Placebo Placebo Group 1 Intervention

Participants received placebo tablets matching TAK-861, orally, twice daily (BID), from Days 1 to 56.

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

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]

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]

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.

sleepwakeadvisor.com

sleepwakeadvisor.com/reports/tak-861-improves-wakefulness-sleepiness-cataplexy-in-narcolepsy/

TAK-861 Improves Wakefulness, Subjective Sleepiness ...

Relative to placebo, TAK-861 significantly increased sleep onset latency and decreased subjective sleepiness across all dosages.

6.

nature.com

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

TAK-861, a potent, orally available orexin receptor 2 ...

TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes ...