Primary: - To assess the effect of TAK-861 on excessive daytime sleepiness (EDS) as measured by sleep latency from the Maintenance of Wakefulness Test (MWT).Please refer to the Study protocol for detailed description on the secondary Objective of…
ID
Source
Brief title
Condition
- Sleep disturbances (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline to Week 8 in mean sleep latency from the MWT.
Secondary outcome
- Change from baseline to Week 8 in ESS total score.
- WCR at Week 8
- Occurrence of at least 1 treatment-emergent adverse event (TEAE).
Please refer to protocol section for a detailed Secondary study parameters.
Background summary
This study is designed to evaluate the efficacy, safety, and tolerability of
multiple oral doses of TAK-861 in participants with narcolepsy type 1 (NT1).
Narcolepsy with cataplexy, or NT1, has been defined by International
Classification of Sleep Disorders, 3rd Edition (ICSD-3) criteria as having low
levels of orexin (OX) in the cerebrospinal fluid (CSF) (<=110 pg/mL, or less
than one-third of normal levels), resulting from the nearly complete loss of
OX-producing neurons. An orexin type-2 receptor (OX2R) agonist is thus the
first approach to directly address the loss of OX peptide in the brain in as it
may restore OX2R signaling at the postsynaptic receptors and may be more
effective than current therapies in treating the entire NT1 pentad, especially
EDS and cataplexy.
Please refer to the Introduction section, study background detailed in the
study protocol.
Study objective
Primary:
- To assess the effect of TAK-861 on excessive daytime sleepiness (EDS)
as measured by sleep latency from the Maintenance of Wakefulness Test (MWT).
Please refer to the Study protocol for detailed description on the secondary
Objective of the study.
Study design
This is a randomized, double-blind, placebo-controlled, multicenter, 8-week
parallel group study to evaluate the efficacy, safety, and tolerability of 4
oral dose regimens of TAK-861.
Please refer to the Study Design detailed in the Study protocol.
Intervention
Arm 1 - dose of 1mg app 3 hours apart
Arm 2 - dose of 4mg app 3h apart
Arm 3 - dose 2mg follow 5mg app 3h apart
Arm 4 dose 7mg daily
Arm 5 matching placebo
As study is blinded patients in Arm 1-4 also will receive placebo
Study burden and risks
Section E describes the burden and risks of participation as well as the
(possible) benefit.
Review of available nonclinical and clinical data, including the nonserious,
mild TEAEs reported in ongoing Study TAK-861-1001, supports a favorable
benefit-risk ratio for this study with TAK-861. Refer to the latest version of
the TAK-861 IB for the overall benefit/risk assessment and the most current
information regarding drug metabolism, PK, efficacy, and safety of TAK-861.
Please refer to protocol section 2.3 for a detailed benefit/risk assessment.
Hayden Avenue 95
Lexington MA 02421
US
Hayden Avenue 95
Lexington MA 02421
US
Listed location countries
Age
Inclusion criteria
1. The participant is aged 18 to 70 years, inclusive, at the time of signing
the informed consent form (ICF).
2. The participant has body mass index (BMI) within the range 18 to 40 kilogram
per square meter [kg/m^2] (inclusive).
3. The participant has an International Classification of Sleep Disorders, 3rd
Edition (ICSD-3) diagnosis of narcolepsy type 1 (NT1) by polysomnography
(PSG)/Multiple Sleep Latency Test (MSLT), performed within the past 10 years.
4. The participant is positive for the human leukocyte antigen (HLA) genotype
HLA-DQB1*06:02 or results from cerebrospinal fluid (CSF) testing indicate the
participant's CSF orexin (OX)/hypocretin-1 concentration is <110 picograms per
milliliter ([pg/mL] (or less than one-third of the mean values obtained in
normal participants within the same standardized assay).
Exclusion criteria
1. The participant has a current medical disorder, other than narcolepsy with
cataplexy, associated with EDS.
2. The participant has medically significant hepatic or thyroid disease.
3. The participant has a history of cancer in the past 5 years (does not apply
to participants with carcinoma in situ that has been resolved without further
treatment or basal cell cancer)
4. The participant has clinically significant coronary artery disease, a
history of myocardial infarction, clinically significant angina, clinically
significant cardiac rhythm abnormality, or heart failure.
5. The participant has a clinically significant history of head injury or head
trauma.
6. The participant has history of epilepsy, seizure, or convulsion, or has a
family history of inherited disorders associated with seizure (except for a
single febrile seizure in childhood).
7. The participant has one or more of the following psychiatric disorders:
a. Any current unstable psychiatric disorder.
b. 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, intellectual disability, 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).
c. Current diagnosis or history of substance use disorder as defined in the
DSM-5.
d. Current active major depressive episode (MDE) or who have had an active MDE
in the past 6 months.
8. The participant has a history of cerebral ischemia, transient ischemicattack
(<5 years ago), intracranial aneurysm, or arteriovenous malformation.
9. The participant has a positive test result for hepatitis B surface antigen,
hepatitis C virus antibody, or human immunodeficiency virus(HIV)
antibody/antigen.
10. The participant's renal creatinine clearance (Cockcroft-Gault Equation) is
<=50 mL/minute.
11. The participant has alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) values >1.5 times the upper limit of normal (ULN).
12. The participant is considered by the investigator to be at imminent risk of
suicide or injury to self, others, or property, or the participant has
attempted suicide within the past year.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-001654-38-NL |
| ClinicalTrials.gov | NCT05687903 |
| CCMO | NL82933.100.22 |