A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions

Study Overview
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Brief Summary
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The main aim is to evaluate the safety and tolerability of TAK-861 on participants with type 1 and type 2 narcolepsy from previous parent studies, TAK-861-2001 (NCT05687903) and TAK-861-2002 (NCT05687916).

Detailed Description
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The drug being tested in this study is called TAK-861. TAK-861 is being tested to treat people who have narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). This study will look at the safety of TAK-861 along with improvement in narcolepsy symptoms, including excessive daytime sleepiness (EDS) and number of cataplexy episodes. The study will enroll up to 160 patients from controlled studies conducted with TAK-861. Participants will be assigned to one of the treatment groups according to the dose assigned to them in their parent study. Similarly, participants who were previously on a placebo dose will also be assigned to one of the treatment groups randomly. All participants in the study will receive TAK-861. Participants with NT1 will receive the following dose from the parent study: TAK-861 Dose 1 TAK-861 Dose 2 TAK-861 Dose 3 TAK-861 Dose 4 Participants with NT2 will receive either TAK-861 Dose 1 or TAK-861 Dose 2 from the parent study. This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 108 weeks. Participants will make multiple visits to the clinic (with some visits optionally conducted by home health), and will have a follow up assessment 4 weeks after last dose of study drug.

Official Title
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A Long-term Extension Study to Evaluate the Safety and Tolerability of TAK-861 in Participants With Selected Central Hypersomnia Conditions

Conditions
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Narcolepsy Type 1, Narcolepsy Type 2

Intervention / Treatment
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* Drug: TAK-861


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. Participant with a diagnosis of narcolepsy who has completed a controlled study with TAK-861 (including participants diagnosed with NT1 or NT2) and for whom the investigator has no clinical objection to their enrollment. Exclusion criteria: Participant has a moderate or severe ongoing treatment emergent adverse event (TEAE) related to the study drug from the parent study or discontinued because of TEAEs in the parent study. 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. Participant has a risk of suicide according to endorsement of item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) on any visit in the parent TAK-861 study, or has positive answers on item 4 or 5 on the Screening/Baseline C-SSRS Lifetime (based on the past year) during the screening assessment for participants with a dosing gap. 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 current medical disorder, other than narcolepsy with or without cataplexy, associated with excessive daytime sleepiness (EDS). Participant has current active major depressive episode (MDE) or has had an active MDE in the past 6 months. Participant has developed (within the last 6 months) gastrointestinal disease that is expected to influence the absorption of drugs (i.e., a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention). Participant has epilepsy or history of seizure. Participant has any other medical condition, such as anxiety, depression, heart disease, or significant hepatic, pulmonary, or renal disease, that requires them to take excluded medications. Participant has a history of cerebral ischemia, transient ischemic attack (<5 years ago), or cerebral hemorrhage. Participant has a history of myocardial infarction, clinically significant coronary artery disease, clinically significant angina, clinically significant cardiac rhythm abnormality, or heart failure. 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 skin cancer.

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 for up to 104 weeks. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Experimental: TAK-861 Dose 2<br>Participants will receive TAK-861 dose 2 for up to 104 weeks. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Experimental: TAK-861 Dose 3<br>Participants will receive TAK-861 dose 3 for up to 104 weeks. | Drug: TAK-861<br>* TAK-861 tablets<br>|
| Experimental: TAK-861 Dose 4<br>Participants will receive TAK-861 dose 4 for up to 104 weeks. | Drug: TAK-861<br>* TAK-861 tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One or More Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | From signing the informed consent form up to follow-up of 4 weeks after the last dose (Up to approximately 108 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Parent Study in Mean Sleep Latency from the Maintenance of Wakefulness Test (MWT) | The MWT evaluates a person's ability to remain awake under soporific conditions. Because there is no biological measure of wakefulness, wakefulness is measured indirectly by the 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 (parent study), Week 26 (current long-term extension [LTE] study) | 
| Change from Baseline in the Parent Study 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 (parent study); Week 2 through Week 105 (current LTE study) | 
| Change from Baseline in the Parent Study in Weekly Cataplexy Rate (WCR) Using the Patient-reported Cataplexy Diary for Participants With NT1 | Participants with NT1 will complete a daily patient-reported sleep diary to record self-reported narcolepsy symptoms. Participants will record episodes of cataplexy in the diary for over 2-week periods throughout the study. | Baseline (parent study); Week 10 through Week 105 (current LTE study) | 

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