A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy

A Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-994 in Patients With Narcolepsy With or Without Cataplexy (Narcolepsy Type 1 or Narcolepsy Type 2)

The main aims of the study are:

• To check for side effects from TAK-994 and check what dose of TAK-994 participants can tolerate.
• To check what dose range provides adequate relief of narcolepsy symptoms.
• To check how much TAK-994 stays in the blood of participants, over time.

The study will have 4 parts. Participants can only join 1 of the parts.

A. Participants with type 1 narcolepsy will take either TAK-994 or placebo tablets for 28 days. A placebo looks just like TAK-994 but will not have any medicine in it.

B. Participants with type 1 narcolepsy will take 1 of 3 doses of TAK-994 or placebo tablets for 56 days.

C. Participants with type 1 narcolepsy in China only will take TAK-994 or placebo tablets for 56 days.

D. Participants with type 2 narcolepsy will take either TAK-994 or placebo tablets for 28 days.

Study Overview

• Status: Terminated
• Conditions: Narcolepsy Type 1 (NT1); Narcolepsy Type 2 (NT2)
• Intervention / Treatment: Drug: TAK-994; Drug: Placebo

Detailed Description

The drug being tested in this study is called TAK-994. TAK-994 is being tested in participants with NT1 and NT2.

The study will enroll up to approximately 202 participants. The study has 4 Parts: Parts A, B, C (China only) and D. Part A - Part A has 2 cohorts [Cohorts (A1a and A1b) A2] In both of these Cohorts, participants will be randomly assigned (by chance, like flipping a coin) in a 2:1 ratio to receive TAK-994 or placebo up to 28 days:

• Part B: In Part B, participants will be randomized in 1:1:1:1 ratio in four parallel arms to receive TAK-994 Dose 1, 2 or 3 or placebo for 56 days. Depending upon their eligibility participants completing Part B of the study treatment will be enrolled to participate in an Extension study.
• Part C: In Part C, participants only from China will be enrolled and randomized in a 2:1 ratio to receive TAK-994 and placebo for 56 days.
• Part D: Participants will be included in two cohorts [Cohorts (D1a and D1b) and D2] and will be randomized in 2:1 ratio to receive TAK-994 or placebo for 28 days. The dose will be selected based on the safety and tolerability in Part A.

This multi-center trial will be conducted in the United States, Japan, China, Italy, France, and European Union. The overall duration of the study is 63 days. Participants will be followed up for 7 days after the last dose of study drug.

• Study Type: Interventional
• Enrollment (Actual): 257
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K2A3Z8
      • West Ottawa Sleep Centre
    • Toronto, Ontario, Canada, M4P 1P2
      • Toronto Sleep Institute
    • Toronto, Ontario, Canada, M5S 3A3
      • Jodha Tishon Inc.
• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital Capital Medical University
  • Guangdong
    • Tianhe, Guangdong, China, 510630
      • The First Affiliated Hospital of Jinan University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University
• Czechia
  • Hradec Kralove, Czechia, 50333
    • Fakultni nemocnice Hradec Kralove
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Praha 2, Czechia, 128 21
    • Vseobecna Fakultni Nemocnice V Praze
• Finland
  • Helsinki, Finland, 380
    • Terveystalo Helsinki Uniklinikka
  • Turku, Finland, 20521
    • Turku University Hospital
• France
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Gui de Chauliac
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Roger Salengro - CHU Lille
• 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)
  • Roma, Italy, 133
    • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • Enna
    • Troina, Enna, Italy, 94018
      • IRCCS Oasi Maria SS
• Japan
  • Fukuoka-Ken
    • Fukuoka-shi, Fukuoka-Ken, Japan, 812-0025
      • SOUSEIKAI PS Clinic
    • Kitakyushu-shi, Fukuoka-Ken, Japan, 802-0084
      • YOU ARIYOSHI Sleep Clinic
    • Kurume-shi, Fukuoka-Ken, Japan, 830-0011
      • Kurume University Hospital
  • Kanagawa-Ken
    • Yokohama-shi, Kanagawa-Ken, Japan, 223-0059
      • Kaiseikai Kita Shin Yokohama Internal Medicine Clinic
  • Kumamoto-Ken
    • Kumamoto-shi, Kumamoto-Ken, Japan, 862-0954
      • Howakai Kuwamizu Hospital
  • Nagasaki-Ken
    • Isahaya-shi, Nagasaki-Ken, Japan, 854-0081
      • Jinyukai Kotorii Isahaya Hospital
    • Nagasaki-shi, Nagasaki-Ken, Japan, 850-0045
      • Shunkaikai Inoue Hospital
  • Osaka-Fu
    • Osaka-shi, Osaka-Fu, Japan, 532-0003
      • Gokeikai Osaka Kaisei Hospital
    • Sakai-shi, Osaka-Fu, Japan, 599-8263
      • Kyowakai Hannan Hospital
  • Tokyo-To
    • Bunkyo-ku, Tokyo-To, Japan, 112-0012
      • Koishikawa Tokyo Hospital
    • Itabashi-ku, Tokyo-To, Japan, 173-8610
      • Nihon University Itabashi Hospital
    • Shibuya-ku, Tokyo-To, Japan, 151-0053
      • Yoyogi Sleep Disorder Center
    • Shinagawa-ku, Tokyo-To, Japan, 140-0011
      • Sleep Support Clinic
    • Shinagawa-ku, Tokyo-To, Japan, 141-6003
      • Sleep & Stress Clinic
    • Sumida-ku, Tokyo-To, Japan, 130-0004
      • Sumida Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Keimyung University Dongsan Hospital
  • Gyeonggi-do
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
      • The Catholic University of Korea, St. Vincent's Hospital
• Netherlands
  • Heemstede, Netherlands, 2103 SW
    • Stichting Epilepsie Instelling Nederland, Heemstede
  • Heeze, Netherlands, 5591 VE
    • Kempenhaeghe, Heeze
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic de Barcelona
  • Madrid, Spain, 28043
    • Hospital Vithas Nuestra Senora de America
  • Alava
    • Vitoria, Alava, Spain, 1004
      • Hospital Universitario Araba Sede Santiago
  • Castellon
    • Castellon de la Plana, Castellon, Spain, 12004
      • Hospital General de Castellon
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • Wright Clinical Research
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • 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, 92128
      • Pacific Research Network, Inc
    • Santa Ana, California, United States, 92705
      • SDS Clinical Trials, Inc.
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Alpine Clinical Research Center
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves Sleep Disorders and Research Center
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Miami, Florida, United States, 33126
      • Sleep Medicine Specialists of South Florida
    • Miami, Florida, United States, 33186
      • Clinical Trials of Florida
    • Tampa, Florida, United States, 33624
      • JSV Clinical Research Study, Inc
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research, Inc.
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta, LLC
    • Macon, Georgia, United States, 31210
      • Sleep Practitioners, LLC
    • Stockbridge, Georgia, United States, 30281
      • Global Research Associates
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Sleep Disorder Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute, Inc.
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Newton, Massachusetts, United States, 02459
      • Neurocare, Inc., dba Neurocare Center for Research
  • North Carolina
    • Denver, North Carolina, United States, 28037
      • Research Carolina Elite LLC
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • 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
    • Dublin, Ohio, United States, 43017
      • Ohio Sleep Medicine and Neuroscience Institute
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Respiratory Specialists
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants, LLC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center
    • Sugar Land, Texas, United States, 77478
      • Comprehensive Sleep Medicine Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has a diagnosis of narcolepsy type 1 (NT1) (Parts A-C) or NT2 (Part D) by polysomnography (PSG)/ multiple sleep latency test (MSLT) performed within the past 10 years meeting the minimal acceptable criteria for the proper performance of the PSG/MSLT as outlined by the International Classification of Sleep Disorders, 3rd edition criteria.
2. The participant's Epworth Sleepiness Scale (ESS) score must be greater than or equal to (>=) 10 at Day -1.
3. Must be willing to discontinue all medications used for the treatment of NT1/NT2.
4. The human leukocyte antigen (HLA) genotype: Part A: should test positive for human leukocyte antigen (HLADQB1)* 06:02 (PARTs A-C)- (positive results for either homozygous or heterozygous alleles will be considered "positive" and acceptable). However, if the HLA test is negative (i.e. negative for the heterozygous allele) and the PI feels strongly that the participant has narcolepsy with cataplexy (NT1) then a discussion should be initiated between the PI and the sponsor or designee about the advisability of doing a spinal tap to determine the participant's cerebrospinal fluid (CSF) orexin-1 (OX-1) level. If the CSF result shows the orexin 1 (OX-1) concentration is either less than or equal to<110 pg/mL, or less than one-third of mean values obtained in normal participants with the same standardized assay, then the diagnosis of NT1 is established allowing the participant to be enrolled and randomized, If the CSF OX-1 concentration is >110 pg/mL then the participant will not be allowed to continue in the study .
5. For Parts A, B, and C, during the screening period, participant, must have >=4 partial or complete episodes of cataplexy/week (WCR), and >=4 partial or complete episodes of cataplexy/week during the screening period when off of anticataplexy medications, averaged over 2 weeks (14 consecutive days) minimum. WCR recording taken during following period will be considered for study eligibility: after the participant has stopped taking anticataplexy medications for at least 7 days (minimum 7-day washout) and study Day -2.

Exclusion Criteria:

1. Has a risk of suicide according to endorsement of Item 4 or 5 of the screening/baseline visit Columbia suicide severity rating scale (C-SSRS) or has made a suicide attempt in the previous 12 months.
2. Is an excessive (>600 mg/day) caffeine user 1 week before to the study screening.
3. Has a history of cancer (except carcinoma in situ that has been resolved without further treatment or basal cell skin cancer); past or current epilepsy, seizure; a lifetime history of major psychiatric disorder other than depression or anxiety; a clinically significant history of head injury or head trauma; a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation; known coronary artery disease, a history of myocardial infarction, angina, cardiac rhythm abnormality, or heart failure; or current or recent (within 6 months) gastrointestinal disease expected to influence the absorption of drugs. Any history of Roux-en-Y gastric bypass is considered exclusionary and any other surgical intervention that may influence the absorption of drugs should be discussed and approved by the sponsor or designee before enrolling the participants.
4. Has a medical disorder, other than narcolepsy, associated with EDS. This includes clinically significant moderate to severe obstructive sleep apnea and/or with or without treatment with mandibular advanced device hypoglossal nerve stimulation and/or positive airway pressure (PAP) therapy) and/or restless legs syndrome (RLS)/periodic limb movement disorder that has a significant impact on daytime sleepiness. This is evidenced by a clinical history of sleep apnea syndrome (loud snoring with observed respiratory pauses in the absence of nPSG) and/or RLS causing historical sleep onset/maintenance insomnia with resultant insufficient sleep. Or any as evaluated during the clinical interview at screening. pPast PSG data demonstrating any of the following sleep disturbances: apnea Hypopnea Index ≥15 or apnea index ≥10, an oxygen saturation of <80 for >10 seconds, periodic leg movement arousal index of ≥15/h) or as evaluated on interview at the time of screening. Asshould be considered exclusionary unless, based on a clinical evaluation by the investigator, a meaningful change in clinical status has occurred that would impact the results. Because nPSG data is obtained on Day -2, subjects may fail screening if criteria are not meet on the Day -2 nPSG.
5. Has a usual bedtime later than 2400 (12:00 AM, midnight) or an occupation requiring nighttime shift work or variable shift work within the past 6 months or travel within more than 3 time zones, within 14 days before Study Day -2.
6. Has a nicotine dependence that is likely to have an effect on sleep (e.g., a participant who routinely awakens at night to smoke) and/or an unwillingness to discontinue all smoking and nicotine use during the confinement portions of the study. Participants undergoing optional CSF collection.
7. Has a local infection at the puncture site.
8. Has developed signs of lumbar radiculopathy, including lower extremity pain and paresthesia.
9. Has any known focal neurological deficit that might suggest an increase in intracranial pressure.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A, Cohorts A1a and Cohorts A1b and A2 (Optional), NT1 Participants: Placebo; TAK-994 placebo-matching tablets for 28 days, in participants with NT1.	Drug: Placebo; TAK-994 placebo-matching tablets.
Experimental: Part A, Cohort A1a, NT1 Participants: TAK-994 TBD; TAK-994, tablets, dose level 1 for 28 days, in participants with NT1.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part A, Cohort A1b, NT1 Participants: TAK-994; TAK-994 tablets, dose to be determined (TBD) based on safety, tolerability and/or efficacy in Cohort A1a participants with NT1.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part A, Cohort A2 (Optional), NT1 Participants: TAK-994 TBD; TAK-994 tablets, TBD based on safety, tolerability and/or efficacy data of Cohort A1, for 28 days.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part B, NT1 Participants: TAK-994 Dose 1; TAK-994 dose 1, tablets, for 56 days in participants with NT1.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part B, NT1 Participants: TAK-994 Dose 2; TAK-994 dose 2, tablets, for 56 days in participants with NT1.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part B, NT1 Participants: TAK-994 Dose 3; TAK-994 dose 3, tablets, 56 days in participants with NT1.	Drug: TAK-994; TAK-994 tablets.
Placebo Comparator: Part B, NT1 Participants: Placebo; TAK-994 placebo-matching tablets for 56 days in participants with NT1.	Drug: Placebo; TAK-994 placebo-matching tablets.
Placebo Comparator: Part C, NT1 Participants in China: Placebo; TAK-994 placebo-matching tablets for 56 days, in participants with NT1 in China.	Drug: Placebo; TAK-994 placebo-matching tablets.
Experimental: Part C, NT1 Participants in China: TAK-994; TAK-994 tablets, dose TBD based on safety and tolerability in Part B, for 56 days in participants with NT1 in China.	Drug: TAK-994; TAK-994 tablets.
Placebo Comparator: Part D, Cohort D1a, D1b and D2, NT2 Participants: Placebo; TAK-994 placebo-matching tablets for 28 days, in participants with NT2.	Drug: Placebo; TAK-994 placebo-matching tablets.
Experimental: Part D, Cohort D1a, NT2 Participants: TAK-994; TAK-994 tablets, dose TBD based on safety, tolerability and/or efficacy in Part A , for 28 days in participants with NT2.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part D, Cohort D1b, NT2 Participants: TAK-994; TAK-994 tablets, dose TBD based on safety and/or tolerability efficacy in Cohort D1a participants with NT2.	Drug: TAK-994; TAK-994 tablets.
Experimental: Part D, Cohort D2, NT2 Participants (Optional) : TAK-994 TBD; TAK-994 tablets, TBD based on safety, tolerability and/or efficacy data of Cohort D1, for 28 days.	Drug: TAK-994; TAK-994 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and D: Number of Participants who Experience at least 1 Treatment Emergent Adverse Events (TEAEs) During the Study	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 (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.	First dose of study treatment to end of study follow-up (up to Day 35)
Parts A and D: Number of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at least Once Postdose During the Study	Standard safety laboratory values (serum chemistry, hematology, and urine analysis) will be collected and compared to pre-specified criteria for markedly abnormal values throughout the study.	Baseline up to Day 35
Parts A and D: Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at least Once Postdose During the Study	Vital signs (body temperature, heart rate, respiratory rate, sitting blood pressure and pulse) will be collected and compared to pre-specified criteria for markedly abnormal values throughout the study.	Baseline up to Day 35
Parts A and D: Number of Participants who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at least Once Postdose During the Study	A 12 lead ECG will be performed, the ECG values will be compared to pre-specified criteria for markedly abnormal values.	Baseline up to Day 35
Parts B and C: Change From Baseline in Average Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT)	The MWT is a validated, objective measure that evaluates a person's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants will be instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session will be recorded on electroencephalography (EEG). If no sleep has been observed according to these rules, then the latency will be defined as 40 minutes.	Baseline and Week 8 (Day 56)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and D: Day 1, Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994		Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Parts A and D: Day 1, Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994		Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Parts A and D: Day 1, AUC(0-last): Area Under the Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration After Single Dose of TAK-994		Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Parts A and D: Day 28, Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-994		Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Parts A and D: Day 28, Tmax: Time of First Occurrence of Cmax After Multiple Doses of TAK-994		Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Parts A and D: Day 28, AUC(0-t): Area Under the Concentration-time Curve from Time 0 to Time tau Over a Dosing Interval of TAK-994		Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Parts B and C: Change From Baseline in Subjective Daytime Sleepiness as Assessed by ESS Score	The ESS is a subjective, self-administered, validated scale (scored 0 to 3) to respond to each of the 8 questions of daily life that asks them how likely they are to fall asleep in those situations. 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 and Week 8 (Day 56)
Parts B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) as Reported in the Patient-Reported Sleep Diary	Participants will complete a daily patient-reported sleep diary to record self-reported narcolepsy symptoms. Participants will record episodes of cataplexy in the diary. The total number of events averaged for a week will be reported.	Baseline and Week 8 (Day 56)
Parts B and C: Number of Participants who Experience at least 1 Treatment Emergent Adverse Events (TEAEs) During the Study	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 (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.	First dose of study treatment to end of study follow-up (Up to Day 63)
Parts B and C: Number of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at least Once Postdose During the Study	Standard safety laboratory values (serum chemistry, hematology, and urine analysis) will be collected and compared to pre-specified criteria for markedly abnormal values throughout the study.	Baseline up to Day 63
Parts B and C: Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at least Once Postdose During the Study	Vital signs (body temperature, heart rate, respiratory rate, sitting blood pressure and pulse) will be collected and compared to pre-specified criteria for markedly abnormal values throughout the study.	Baseline up to Day 63
Parts B and C: Number of Participants who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at least Once Postdose During the Study	A 12 lead ECG will be performed, the ECG values will be compared to pre-specified criteria for markedly abnormal values.	Baseline up to Day 63
Change from Baseline in Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT)	The MWT is a validated, objective measure that evaluates a person's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants will be instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session will be recorded on electroencephalography (EEG). If no sleep has been observed according to these rules, then the latency will be defined as 40 minutes.	Baseline up to Week 4
Change From Baseline in Subjective Daytime Sleepiness as Assessed by Epworth Sleepiness Scale (ESS) Score	The ESS is a subjective, self-administered, validated scale (scored 0 to 3) to respond to each of the 8 questions of daily life that asks them how likely they are to fall asleep in those situations. 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 up to Week 4
Parts A, B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) as Reported in the Patient-Reported Sleep Diary	Participants will complete a daily patient-reported sleep diary to record self-reported narcolepsy symptoms. Participants will record episodes of cataplexy in the diary. The total number of events per week will be calculated.	Baseline up to Week 4

Collaborators and Investigators

• Sponsor: 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): February 27, 2020
• Primary Completion (Actual): November 5, 2021
• Study Completion (Actual): November 5, 2021

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (Actual): September 20, 2019

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 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-994-1501; JapicCTI-205178 (Registry Identifier: JapicCTI); 2020-000777-24 (Registry Identifier: EudraCT); U1111-1240-0346 (Registry Identifier: WHO)

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