TAK-861 for Narcolepsy
Recruiting in Palo Alto (17 mi)
+64 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Takeda
Must be taking: TAK-861
Must not be taking: Antidepressants, Anticonvulsants
Disqualifiers: Suicide risk, Liver issues, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing TAK-861, a new drug, on people with type 1 and type 2 narcolepsy. The goal is to see if it can help reduce excessive daytime sleepiness and sudden muscle weakness. The study will involve up to 160 participants from previous studies and will last about two years.
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.
How is the drug TAK-861 different from other narcolepsy treatments?
TAK-861 is unique because it is an orexin 2 receptor agonist, which means it specifically targets and activates receptors in the brain that help regulate wakefulness, potentially offering a more targeted approach to treating narcolepsy compared to other treatments that may have broader effects or more side effects.
12345Eligibility Criteria
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.
+9 more
Trial Timeline
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)
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: TAK-861 Dose 2Experimental Treatment1 Intervention
Participants will receive TAK-861 dose 2 for up to approximately 5 years.
Group II: TAK-861 Dose 1Experimental Treatment1 Intervention
Participants will receive TAK-861 dose 1 for up to approximately 5 years.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
ARSM Research, LLCHuntersville, NC
Neurocare IncNewton, MA
University of Colorado HospitalSaint Louis, MO
The Cleveland Clinic FoundationCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?
TakedaLead Sponsor
References
Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist. [2022]TAK-925, a potent, selective, and brain-penetrant orexin 2 receptor (OX2R) agonist, [methyl (2R,3S)-3-((methylsulfonyl)amino)-2-(((cis-4-phenylcyclohexyl)oxy)methyl)piperidine-1-carboxylate, 16], was identified through the optimization of compound 2, which was discovered by a high throughput screening (HTS) campaign. Subcutaneous administration of compound 16 produced wake-promoting effects in mice during the sleep phase. Compound 16 (TAK-925) is being developed for the treatment of narcolepsy and other related disorders.
Trace Amine-Associated Receptor 1 Agonists as Narcolepsy Therapeutics. [2018]Narcolepsy, a disorder of rapid eye movement (REM) sleep, is characterized by excessive daytime sleepiness and cataplexy, a loss of muscle tone triggered by emotional stimulation. Current narcolepsy pharmacotherapeutics include controlled substances with abuse potential or drugs with undesirable side effects. As partial agonists at trace amine-associated receptor 1 (TAAR1) promote wakefulness in mice and rats, we evaluated whether TAAR1 agonism had beneficial effects in two mouse models of narcolepsy.
Danavorexton, a selective orexin 2 receptor agonist, provides a symptomatic improvement in a narcolepsy mouse model. [2022]Narcolepsy type 1 (NT1), caused by loss of orexin neurons, is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, hypnagogic/hypnopompic hallucinations and sleep paralysis, as well as a high risk of obesity. Danavorexton (TAK-925) is a novel brain-penetrant orexin 2 receptor (OX2R)-selective agonist currently being evaluated in clinical trials for the treatment of hypersomnia disorders including NT1. Thus, detailed characterization of danavorexton is critical for validating therapeutic potential of OX2R-selective agonists. Here, we report preclinical characteristics of danavorexton as a therapeutic drug for NT1. Danavorexton showed rapid association/dissociation kinetics to OX2R. The activation mode of endogenous OX2R by danavorexton and orexin peptide was very similar in an electrophysiological analysis. In orexin/ataxin-3 mice, a mouse model of NT1, danavorexton promoted wakefulness, and ameliorated fragmentation of wakefulness during the active phase after both acute and repeated administration, suggesting a low risk of receptor desensitization. Electroencephalogram (EEG) power spectral analysis revealed that danavorexton, but not modafinil, normalized dysregulated EEG power spectrum in orexin/ataxin-3 mice during the active phase. Finally, repeated administration of danavorexton significantly suppressed the body weight gain in orexin/ataxin-3 mice. Danavorexton may have the potential to treat multiple symptoms of NT1. These preclinical findings, together with upcoming clinical observations of danavorexton, could improve our understanding of the pathophysiology of NT1 and therapeutic potential of OX2R agonists.
Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice. [2023]The sleep disorder narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK-925 (1-10 mg/kg, s.c.) and ARN-776 (1-10 mg/kg, i.p.) were injected 15 min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc ) and activity were recorded by telemetry; recordings for the first 6 h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the second hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6 h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterised by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the second hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity, and Tsc , suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HCRTR2 agonists.
New developments in the management of narcolepsy. [2020]Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss. Current treatment modalities alleviate the main symptoms of excessive daytime somnolence (EDS) and cataplexy and, to a lesser extent, reduce nocturnal sleep disruption, hypnagogic hallucinations, and sleep paralysis. Sodium oxybate (SXB), a sodium salt of γ hydroxybutyric acid, is a first-line agent for cataplexy and EDS and may help sleep disruption, hypnagogic hallucinations, and sleep paralysis. Various antidepressant medications including norepinephrine serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, and tricyclic antidepressants are second-line agents for treating cataplexy. In addition to SXB, modafinil and armodafinil are first-line agents to treat EDS. Second-line agents for EDS are stimulants such as methylphenidate and extended-release amphetamines. Emerging therapies include non-hypocretin-based therapy, hypocretin-based treatments, and immunotherapy to prevent hypocretin neuronal death. Non-hypocretin-based novel treatments for narcolepsy include pitolisant (BF2.649, tiprolisant); JZP-110 (ADX-N05) for EDS in adults; JZP 13-005 for children; JZP-386, a deuterated sodium oxybate oral suspension; FT 218 an extended-release formulation of SXB; and JNJ-17216498, a new formulation of modafinil. Clinical trials are investigating efficacy and safety of SXB, modafinil, and armodafinil in children. γ-amino butyric acid (GABA) modulation with GABAA receptor agonists clarithromycin and flumazenil may help daytime somnolence. Other drugs investigated include GABAB agonists (baclofen), melanin-concentrating hormone antagonist, and thyrotropin-releasing hormone agonists. Hypocretin-based therapies include hypocretin peptide replacement administered either through an intracerebroventricular route or intranasal route. Hypocretin neuronal transplant and transforming stem cells into hypothalamic neurons are also discussed in this article. Immunotherapy to prevent hypocretin neuronal death is reviewed.