A Study of TAK-861 in Participants With Narcolepsy Type 1

Study Overview
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Brief Summary
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The main aim of this study is to see how TAK-861 works on symptoms of narcolepsy, including excessive daytime sleepiness and cataplexy. Approximately 100 participants will take part in the study across North America, Europe and Asia Pacific. The treatment (TAK-861 or placebo) will be administered for 8 or 12 weeks. After this treatment period the participant will have the option to participate in a separate, long- term extension study during which all participants will be treated with TAK-861.

Detailed Description
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The drug being tested in this study is called TAK-861. This study will look at the effect of TAK-861 on improvement in narcolepsy symptoms, including excessive daytime sleepiness (EDS) and number of cataplexy episodes. The study will enroll approximately 100 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): TAK-861 Dose 1 TAK-861 Dose 2 TAK-861 Dose 3 TAK-861 Dose 4 Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 23 weeks. Participants will make multiple visits to the clinic during the treatment period and then will either enroll in a long-term extension study in which all participants will receive TAK-861 or have 2 final visits 7 and 28 days after last dose of study drug for follow-up assessments.

Official Title
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A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)

Conditions
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Narcolepsy Type 1

Intervention / Treatment
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* Drug: TAK-861
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is aged 18 to 70 years, inclusive, at the time of signing the informed consent form (ICF). Note: In Japan, participants aged 16 to 70 years, inclusive, may be included. The participant has body mass index (BMI) within the range 18 to 40 kilogram per square meter [kg/m^2] (inclusive). 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. 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: The participant has a current medical disorder, other than narcolepsy with cataplexy, associated with EDS. The participant has medically significant hepatic or thyroid disease. 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). The participant has clinically significant coronary artery disease, a history of myocardial infarction, clinically significant angina, clinically significant cardiac rhythm abnormality, or heart failure. The participant has a clinically significant history of head injury or head trauma. 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). 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, 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). Current diagnosis or history of substance use disorder as defined in the DSM-5. Current active major depressive episode (MDE) or who have had an active MDE in the past 6 months. The participant has a history of cerebral ischemia, transient ischemic attack (<5 years ago), intracranial aneurysm, or arteriovenous malformation. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody/antigen. The participant's renal creatinine clearance (Cockcroft-Gault Equation) is ≤50 mL/minute. The participant has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >1.5 times the upper limit of normal (ULN). 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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-861 Dose 1<br>Participants will receive TAK-861 dose 1, orally, from Day 1 up to Weeks 8 or 12. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Experimental: TAK-861 Dose 2<br>Participants will receive TAK-861 dose 2, orally, from Day 1 up to Weeks 8 or 12. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Experimental: TAK-861 Dose 3<br>Participants will receive TAK-861 dose 3, orally, from Day 1 up to Weeks 8 or 12. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Experimental: TAK-861 Dose 4<br>Participants will receive TAK-861 dose 4, orally, from Day 1 up to Weeks 8 or 12. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Placebo Comparator: Placebo<br>Participants will receive TAK-861 matching placebo tablets, orally, from Day 1 up to Weeks 8 or 12. | Drug: Placebo<br>* TAK-861 placebo matching tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 8 in Mean Sleep Latency from the Maintenance of Wakefulness Test (MWT) | The MWT evaluates a person's ability to remain awake under soporific conditions for a defined period of time. Because there is no biological measure of wakefulness, wakefulness is measured indirectly by the inability or delayed tendency to fall asleep. This tendency to fall asleep is measured via electroencephalography-derived sleep latency in the MWT. The MWT consists of four 40-minute sessions done 2 hours apart. Sleep latency in each session will be recorded. Participants will be required to stay awake in between the 4 sessions. | Baseline, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 8 in Epworth Sleepiness Scale (ESS) Total Score | The ESS provides individuals with 8 different situations of daily life and asks them how likely they are to fall asleep in those situations (scored 0 to 3) and to try to imagine their likelihood of dozing even if they have not actually been in the identical situation; the scores are summed to give an overall score of 0 to 24. Higher scores indicate stronger subjective daytime sleepiness, and scores below 10 are considered to be within the normal range. | Baseline, Week 8 | 
| Weekly Cataplexy Rate at Week 8 |  | Week 8 | 
| Occurrence of at Least One Related Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product. A TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product. | Baseline up to approximately 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy