TAK-861 for Narcolepsy

No longer recruiting at 63 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Disqualifiers: Epilepsy, Seizure, Schizophrenia, Bipolar, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of the drug TAK-861 in treating narcolepsy, with a focus on reducing excessive daytime sleepiness. Researchers will divide participants into three groups: two will receive different doses of TAK-861, and one will receive a placebo (a pill with no active drug) for 8 weeks. The trial is designed for individuals diagnosed with narcolepsy type 2 (a sleep disorder without cataplexy) who have difficulty staying awake during the day. Participants must complete some questionnaires during the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Do I need to stop 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.

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

Research shows that TAK-861, a treatment for narcolepsy, has been studied for its safety and effects on symptoms like excessive daytime sleepiness. Studies found that TAK-861 can help people with narcolepsy stay awake and feel less sleepy. Previous trials demonstrated that participants tolerated TAK-861 well, with no major safety issues reported.

In one study involving people with narcolepsy, TAK-861 significantly improved their ability to stay awake and reduced their sleepiness. Participants did not report any serious side effects, indicating the treatment is well-tolerated. Another study in animals also showed positive effects, such as improved symptoms similar to narcolepsy, without any severe negative effects.

While TAK-861 is still under investigation, these findings suggest it is generally safe for humans at the doses tested. This information may help prospective trial participants feel more confident about the safety of TAK-861. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for narcolepsy?

Researchers are excited about TAK-861 for narcolepsy because it offers a novel approach to treating this sleep disorder. Unlike traditional treatments that often focus on stimulating wakefulness or managing symptoms with medications like modafinil or sodium oxybate, TAK-861 targets specific neurological pathways to potentially improve sleep regulation more directly. This new mechanism of action could lead to better management of narcolepsy symptoms with fewer side effects. Additionally, TAK-861 is administered orally, making it convenient for patients to use in their daily routine.

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

Research shows that TAK-861, which participants in this trial may receive, may help treat narcolepsy symptoms, such as excessive daytime sleepiness. Studies have found that TAK-861 helps people stay awake and feel less sleepy compared to those who took a placebo, a pill with no active medicine. It also delays the onset of sleep, allowing individuals to stay awake longer. TAK-861 works by targeting a part of the brain that controls sleep and wakefulness. These findings suggest that TAK-861 could effectively manage narcolepsy symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

Adults aged 18-70 with a diagnosis of Narcolepsy Type 2 (NT2) can join this trial. They must have had a sleep study in the last 5 years confirming NT2, or they may undergo another one if needed. People with other disorders causing excessive daytime sleepiness, certain psychiatric conditions, substance use disorders, or recent major surgery are not eligible.

Inclusion Criteria

I have been diagnosed with narcolepsy type 2 in the last 5 years.

Exclusion Criteria

I have a condition causing excessive daytime sleepiness, not including narcolepsy without cataplexy.

The participant has one or more of the following psychiatric disorders: Any current unstable psychiatric disorder, current or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), current diagnosis or history of substance use disorder as defined in the DSM-5. (Note: If the history of substance use disorder is more than 12 months before baseline, the participant may be allowed to enroll in the study after consultation with the sponsor or designee. (Participant must also have negative urine drug screen at the screening and Day -2 visit.), current active major depressive episode (MDE) or who have had an active MDE in the past 6 months.

I have had a stroke, mini-stroke, brain aneurysm, or blood vessel malformation 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 or placebo for 8 weeks to evaluate efficacy, safety, and tolerability

8 weeks

Regular visits for monitoring and questionnaire completion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• TAK-861

Trial Overview

The trial is testing TAK-861 to see if it helps with narcolepsy symptoms like staying awake during the day. Participants will be randomly placed into three groups to receive either TAK-861 at two different doses or a placebo for eight weeks and complete questionnaires about their condition.

How Is the Trial Designed?

Group I: TAK-861 2 milligrams (mg) BID Experimental Treatment 1 Intervention

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

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

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

Group III: 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

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 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]

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]

In a multicenter trial involving 285 patients with narcolepsy, sodium oxybate significantly improved quality of life, as measured by the Functional Outcomes of Sleep Questionnaire, compared to placebo.

The improvements were dose-related, with notable enhancements in various aspects of daily functioning, including activity level and social outcomes, indicating that sodium oxybate can effectively address symptoms of narcolepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial evaluating the effectiveness of sodium oxybate therapy on quality of life in narcolepsy. Weaver, TE., Cuellar, N.[2019]

In a study of 92 patients with narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia, significant improvements in patient-reported outcomes related to sleepiness and depression were observed after treatment, regardless of the specific diagnosis or treatment regimen used.

Higher standardized drug doses were associated with worsening depression scores, suggesting that careful consideration of drug burden is important in managing these patients' symptoms effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pharmacotherapy Treatment on Patient-Reported Outcomes in a Narcolepsy and Idiopathic Hypersomnia Cohort. Pascoe, M., Bena, J., Foldvary-Schaefer, N.[2023]

Citations

1.

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 ...

2.

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 ...

3.

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 ...

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 ...