A Study of TAK-994 in Adults With Narcolepsy

Study Overview
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Brief Summary
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Adults with narcolepsy who have completed the TAK-994-1501 study will be able to take part in this study. The main aim of this study is to check if participants have side effects from TAK-994. Participants will take one of 3 different TAK-994 dose for 8 weeks. Then, half the participants will continue with their dose of TAK-994 and half will take a placebo. In this study, a placebo will look like a TAK-994 tablet but will not have any medicine in it. Participants will take TAK-994 or placebo for 4 weeks. Participants will visit the clinic for a final check-up 2 weeks after their last dose of TAK-994 or placebo. The study doctors will check for side effects from TAK-994 and placebo throughout the study. Participants will continue to record any narcolepsy symptoms as they did in Part B of the TAK 994-1501 study.

Detailed Description
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The drug being tested in the study is called TAK-994. TAK-994, is being tested to treat participants with NT1. Participants who completed Part B of TAK-994-1501(NCT04096560) will be eligible for enrollment in this study. This study will enroll approximately 112 patients to receive one of three different TAK 994 dose for 8 weeks (active drug extension period). Participants will be randomly assigned to one of these different TAK 994 doses which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). Following the 8-week Active Drug Extension Period, participants will continue into a 4-week Double-blind Randomized Withdrawal Period and will receive TAK-994 or Placebo. Participants randomized to TAK-994 will continue to receive the same dose as before. This multi-center trial will be conducted worldwide. The duration of treatment in this study is 12 weeks plus a 2 week safety follow up period. Participants will visit the clinic 10 times after the first dosing.

Official Title
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A Dose-Blind Extension Study With Double-blind, Placebo-Controlled, Randomized Withdrawal Period to Evaluate the Safety and Explore the Pharmacokinetics and Pharmacodynamics of TAK-994 in Adults With Narcolepsy With Cataplexy (Narcolepsy Type 1)

Conditions
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Narcolepsy Type 1 (NT 1)

Intervention / Treatment
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* Drug: TAK-994
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Participant with a diagnosis of Narcolepsy Type 1 (NT1) who has completed TAK-994-1501 Part B before enrollment (which will occur immediately following the final TAK-994-1501 assessments), and for whom the investigator has no clinical objection they be enrolled. Exclusion Criteria: 1. Participant has a clinically significant moderate or severe ongoing AE related to the study drug from the prior study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Drug Extension Period: TAK-994 30 mg<br>TAK-994 30 mg, twice daily (BID) tablets, orally, from Day 1 (Day 57 of previous study) to Day 56 in the Active Drug Extension Period. | Drug: TAK-994<br>* TAK-994 tablets.<br>|
| Experimental: Active Drug Extension Period: TAK-994 90 mg<br>TAK-994 90 mg, BID, tablets, orally, from Day 1 (Day 57 of previous study) to Day 56 in the Active Drug Extension Period. | Drug: TAK-994<br>* TAK-994 tablets.<br>|
| Experimental: Active Drug Extension Period: TAK-994 180 mg<br>TAK-994 180 mg, BID, tablets, orally, from Day 1 (Day 57 of previous study) to Day 56 in the Active Drug Extension Period. | Drug: TAK-994<br>* TAK-994 tablets.<br>|
| Experimental: Double-blind Randomized Withdrawal Period: TAK-994 30 mg<br>Following the Active Drug Extension Period, participants randomized to active treatment 30 mg, BID, meeting eligibility specification and continued to receive same dose (TAK-994, 30 mg, BID, tablets, orally) from Day 57 to Day 84 in the Double-blind Randomized Withdrawal Period. | Drug: TAK-994<br>* TAK-994 tablets.<br>|
| Experimental: Double-blind Randomized Withdrawal Period: TAK-994 90 mg<br>Following the Active Drug Extension Period, participants randomized to active treatment 90 mg, BID, meeting eligibility specification and continued to receive same dose (TAK-994, 90 mg, BID, tablets, orally) from Day 57 to Day 84 in the Double-blind Randomized Withdrawal Period. | Drug: TAK-994<br>* TAK-994 tablets.<br>|
| Experimental: Double-blind Randomized Withdrawal Period: TAK-994 180 mg<br>Following the Active Drug Extension Period, participants randomized to active treatment 180 mg, BID, meeting eligibility specification and continued to receive same dose (TAK-994, 180 mg, BID, tablets, orally) from Day 57 to Day 84 in the Double-blind Randomized Withdrawal Period. | Drug: TAK-994<br>* TAK-994 tablets.<br>|
| Placebo Comparator: Double-blind Randomized Withdrawal Period: Placebo<br>Following the Active Drug Extension Period participants meeting eligibility specification and received placebo-matching tablets for 4 weeks (from Day 57 to Day 84) in the Double-blind Randomized Withdrawal Period. | Drug: Placebo<br>* Placebo-matching 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 Treatment Emergent Adverse Event (TEAE) During the Active Drug Extension Period | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participants 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 (example, 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 AE with an onset that occurs after receiving study drug. | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | 
| Number of Participants With at Least One Post-dose Markedly Abnormal Value (MAV) in Laboratory Test During the Active Drug Extension Period | Clinical laboratory tests included hematology, serum chemistry, and urinalysis. MAV criteria: Hemoglobin <0.8×lower limit of normal (LLN), >1.2×upper limit of normal (ULN); Hematocrit <0.8×LLN, >1.2×ULN; Red blood cells (RBC) count <0.8×LLN, >1.2×ULN; White blood cells (WBC) count <0.5xLLN, >1.5xULN; Platelet count <75x10^9/liter (L), >600x10^9/L; alanine aminotransferase (ALT) >3xULN; aspartate aminotransferase (AST) >3xULN; gamma-glutamyl transferase (GGT) >3xULN; Alkaline phosphatase >3xULN; Total bilirubin >1.5xULN; Albumin <25 grams per liter (g/L); Total protein <0.8xLLN, >1.2xULN; Creatinine >1.5xULN; Blood urea nitrogen >40 milligrams per deciliters (mg/dL); Sodium <130 milliequivalents per liter (mEq/L), >150 mEq/L; Potassium <3.0 millimoles per liter (mmol/L), >5.3 mmol/L; creatine phosphokinase (CPK) >3xULN; Glucose <50 mg/dL, >300 mg/dL; Calcium <7.7 mg/dL, >11.1 mg/dL. Only categories with at least one participant with event are reported. | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | 
| Number of Participants With at Least One Post-dose MAV for Vital Signs During the Active Drug Extension Period | MAV criteria for vital signs were: Pulse <40 beats per minute (bpm), >115 bpm; Systolic blood pressure <90 millimeters of mercury (mmHg), ≥160 mmHg; Diastolic blood pressure <50 mmHg, ≥100 mmHg, Systolic or Diastolic blood pressure change of >20, >30 mmHg from Baseline, Body temperature >38.5 degree Celsius, Respiratory Rate >21 breath/minute. Only categories with at least one participant with event are reported. Baseline for this outcome measure is Day 1 of the Active Drug Extension Period. | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | 
| Number of Participants With at Least One Post-dose MAV for Electrocardiogram (ECG) Parameters During the Active Drug Extension Period | MAV criteria for ECG were: Heart rate <40 bpm, >115 bpm; PR interval ≤80 milliseconds (msec), ≥200 msec; QT interval with Fridericia correction method (QTcF) Interval ≤300 msec, >500 msec or ≥30 msec change from baseline and >450 msec; QRS duration ≤80 msec, ≥180 msec. Only categories with at least one participant with event are reported. | Up to 8 weeks in the Active Drug Extension Period (Weeks 1 to 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One TEAE During the Double-blind Randomized Withdrawal Period | An AE is defined as any untoward medical occurrence in a clinical investigation participants 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 (example, 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 AE with an onset that occurs after receiving study drug. | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | 
| Number of Participants With at Least One Post-dose MAV in Laboratory Test During the Double-blind Randomized Withdrawal Period | Clinical laboratory tests included hematology, serum chemistry, and urinalysis. MAV criteria: Hemoglobin <0.8×LLN, >1.2×ULN; Hematocrit <0.8×LLN, >1.2×ULN; RBC count <0.8×LLN, >1.2×ULN; WBC count <0.5xLLN, >1.5xULN; Platelet count <75x10^9/L, >600x10^9/L; ALT >3xULN; AST >3xULN; GGT >3xULN; Alkaline phosphatase >3xULN; Total bilirubin >1.5xULN; Albumin <25 g/L; Total protein <0.8x LLN, >1.2xULN; Creatinine >1.5xULN; Blood urea nitrogen >40 mg/dL; Sodium <130 mEq/L, >150 mEq/L; Potassium <3.0 mmol/L, >5.3 mmol/L; CPK >3xULN; Glucose <50 mg/dL, >300 mg/dL; Calcium <7.7 mg/dL, >11.1 mg/dL. | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | 
| Number of Participants With at Least One Post-dose MAV for Vital Signs During the Double-blind Randomized Withdrawal Period | MAV criteria for vital signs were: Pulse <40 bpm, >115 bpm; Systolic blood pressure <90 mmHg, ≥160 mmHg; Diastolic blood pressure <50 mmHg, ≥100 mmHg, Systolic or Diastolic blood pressure change of >20, >30 mmHg from Baseline, Body temperature >38.5 degree Celsius, Respiratory Rate >21 breath/minute. Only categories with at least one participant with event are reported. Baseline for this outcome measure is Day 1 of the Double-blind Randomized Withdrawal Period (Day 57 of this study). | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | 
| Number of Participants With at Least One Post-dose MAV for ECG Parameters During the Double-blind Randomized Withdrawal Period | MAV criteria for ECG were: Heart rate <40 bpm, >115 bpm; PR interval ≤80 msec, ≥200 msec; QTcF Interval ≤300 msec, >500 msec or ≥30 msec change from baseline and >450 msec; QRS duration ≤80 msec, ≥180 msec. Only categories with at least one participant with event are reported. | Up to 4 weeks in the Double-blind Randomized Withdrawal Period (Weeks 9 to 12) | 

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