A Study of TAK-994 in Adults With Narcolepsy

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)

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.

Study Overview

• Status: Terminated
• Conditions: Narcolepsy Type 1 (NT 1)
• Intervention / Treatment: Drug: TAK-994; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K2A 3Z3
      • West Ottawa Sleep Centre
    • Toronto, Ontario, Canada, M4P 1P2
      • Toronto Sleep Institute
    • Toronto, Ontario, Canada, M5S 3A3
      • Jodha Tishon Inc.
• Czechia
  • Hradec Kralove, Czechia, 50005
    • Fakultni nemocnice Hradec Kralove Dept of Neurologicka klinika
  • Praha 2, Czechia, 128 21
    • Vseobecna fakultni nemocnice v Praze Dept of Neurologicka klinika 1.LF UK a VFN v Praze
• Finland
  • Helsinki, Finland, 00380
    • Terveystalo Helsinki Uniklinikka 300186257
  • Turku, Finland, 20521
    • Turku University Hospital
• France
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Gui de Chauliac Service de Neurologie
  • Nord
    • Lille Cedex, Nord, France, 59037
      • Hopital Roger Salengro - CHU Lille service de neurologie D
• Hungary
  • Budapest, Hungary, 1012
    • SomnoCenter Budapest
• Italy
  • Bologna, Italy, 40123
    • Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche
  • Milano, Italy, 20127
    • Ospedale San Raffaele (San Raffaele Turro) Clinica Neurologica- Div Malattie del Sonno
  • Roma, Italy, 00133
    • Azienda Ospedaliera Universitaria Policlinico Tor Vergata U.O.C. Neurologia
  • Enna
    • Troina, Enna, Italy, 94018
      • IRCCS Oasi Maria SS 300206751
• Japan
  • Fukuoka-Ken
    • Fukuoka-shi, Fukuoka-Ken, Japan, 812-0025
      • SOUSEIKAI PS Clinic Dept of Internal Medicine
    • Kitakyushu-shi, Fukuoka-Ken, Japan, 802-0084
      • You Ariyoshi Sleep Clinic Dept of Psychiatry
    • Kurume-shi, Fukuoka-Ken, Japan, 830-0011
      • Kurume University Hospital Dept of Neuropsychiatry
  • Kanagawa-Ken
    • Yokohama-shi, Kanagawa-Ken, Japan, 223-0059
      • Kaiseikai Kita Shin Yokohama Internal Medicine Clinic Dept of Internal Medicine
  • Kumamoto-Ken
    • Kumamoto-shi, Kumamoto-Ken, Japan, 862-0954
      • Howakai Kuwamizu Hospital Dept of Internal Medicine
  • Nagasaki-Ken
    • Isahaya-shi, Nagasaki-Ken, Japan, 854-0081
      • Jinyukai Kotorii Isahaya Hospital Dept of Psychiatry
    • Nagasaki-shi, Nagasaki-Ken, Japan, 850-0045
      • Shunkaikai Inoue Hospital Dept of Respiratory Medicine
  • Osaka-Fu
    • Osaka-shi, Osaka-Fu, Japan, 532-0003
      • Gokeikai Osaka Kaisei Hospital Dept of Sleep Medicine
    • Sakai-shi, Osaka-Fu, Japan, 599-8263
      • Kyowakai Hannan Hospital Dept of Psychiatry
  • Tokyo-To
    • Bunkyo-ku, Tokyo-To, Japan, 112-0012
      • Koishikawa Tokyo Hospital Dept of Psychiatry
    • Itabashi-ku, Tokyo-To, Japan, 173-8610
      • Nihon University Itabashi Hospital Dept of Neuropsychiatry
    • Shibuya-ku, Tokyo-To, Japan, 151-0053
      • Yoyogi Sleep Disorder Center Dept of Psychiatry
    • Shinagawa-ku, Tokyo-To, Japan, 140-0011
      • Sleep Support Clinic Dept of Psychosomatic Medicine/Psychiatry
    • Shinagawa-ku, Tokyo-To, Japan, 141-6003
      • Sleep & Stress Clinic Dept of Psychiatry
    • Sumida-ku, Tokyo-To, Japan, 130-0004
      • Sumida Hospital Phase I
• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Keimyung University Dongsan Hospital 300144594
  • Gyeonggi-do
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea, St. Vincent's Hospital 300187879
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona Servicio de Neurologia
  • Madrid, Spain, 28043
    • Hospital Vithas Nuestra Senora de America Neurofisiologia Clinica
  • Alava
    • Vitoria, Alava, Spain, 01004
      • Hospital Universitario Araba Sede Santiago Sleep Unit
  • Castellon
    • Castellon de la Plana, Castellon, Spain, 12004
      • Hospital General de Castellon Servicio de Neurofisiologia
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • Wright Clinical Research
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona 300151190
  • California
    • Bellflower, California, United States, 90706
      • CITrials - Bellflower
    • Los Angeles, California, United States, 90025
      • Santa Monica Clinical Trials
    • Redwood City, California, United States, 94063
      • Stanford School of Medicine
    • San Diego, California, United States, 92103
      • Pacific Research Network, Inc 150118105
    • Santa Ana, California, United States, 92705
      • SDS Clinical Trials, Inc.
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Alpine Clinical Research Center 1024762
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves Sleep Disorders and Research Center 300148510
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Miami, Florida, United States, 33176
      • Sleep Medicine Specialists of South Florida
    • Miami, Florida, United States, 33186
      • Clinical Site Partners, LLC
    • Tampa, Florida, United States, 33624
      • JSV Clinical Research Study, Inc
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC 300127039
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc. 300116336
    • Macon, Georgia, United States, 31210
      • Sleep Practitioners, LLC Macon
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Institute 300169881
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center 150711262
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute, Inc. University of Kansas Hospital
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders" 150119420
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center CardioVascular Institute
  • North Carolina
    • Denver, North Carolina, United States, 28037
      • Research Carolina Elite
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates 300209729
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates,300209729
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research
    • Cincinnati, Ohio, United States, 45245
      • CTI Clinical Research Center
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation 100428
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine and Neuroscience Institute 186
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Respiratory Specialists Berks Schuylkill Respiratory Specialists Ltd
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC) PARENT
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants, LLC 150711087
  • Texas
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center 300151246
    • Sugar Land, Texas, United States, 77478
      • Comprehensive Sleep Medicine Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Drug Extension Period: TAK-994 30 mg; 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; TAK-994 tablets.
Experimental: Active Drug Extension Period: TAK-994 90 mg; 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; TAK-994 tablets.
Experimental: Active Drug Extension Period: TAK-994 180 mg; 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; TAK-994 tablets.
Experimental: Double-blind Randomized Withdrawal Period: TAK-994 30 mg; 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; TAK-994 tablets.
Experimental: Double-blind Randomized Withdrawal Period: TAK-994 90 mg; 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; TAK-994 tablets.
Experimental: Double-blind Randomized Withdrawal Period: TAK-994 180 mg; 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; TAK-994 tablets.
Placebo Comparator: Double-blind Randomized Withdrawal Period: Placebo; 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; Placebo-matching tablets.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): November 3, 2021
• Study Completion (Actual): November 3, 2021

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: March 26, 2021
• First Posted (Actual): March 29, 2021

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Narcolepsy
• Other Study ID Numbers: TAK-994-1504; 2021-000251-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https:// clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/ takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No