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

Primary Purpose

Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2)

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TAK-994
Placebo
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Narcolepsy Type 1 (NT1) focused on measuring Drug therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Wright Clinical Research
  • Mayo Clinic Arizona
  • CITrials - Bellflower
  • Santa Monica Clinical Trials
  • Stanford School of Medicine
  • Pacific Research Network, Inc
  • SDS Clinical Trials, Inc.
  • Alpine Clinical Research Center
  • Delta Waves Sleep Disorders and Research Center
  • St. Francis Medical Institute
  • Sleep Medicine Specialists of South Florida
  • Clinical Trials of Florida
  • JSV Clinical Research Study, Inc
  • Florida Pulmonary Research Institute, LLC
  • NeuroTrials Research, Inc.
  • iResearch Atlanta, LLC
  • Sleep Practitioners, LLC
  • Global Research Associates
  • Hawaii Pacific Neuroscience
  • Lutheran Sleep Disorder Center
  • University of Kansas Medical Center Research Institute, Inc.
  • Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"
  • Boston Children's Hospital
  • Neurocare, Inc., dba Neurocare Center for Research
  • Research Carolina Elite LLC
  • Clinical Research of Gastonia
  • Raleigh Neurology Associates
  • CTI Clinical Research Center
  • Intrepid Research
  • The Cleveland Clinic Foundation
  • Ohio Sleep Medicine and Neuroscience Institute
  • Respiratory Specialists
  • Medical University of South Carolina (MUSC)
  • Bogan Sleep Consultants, LLC
  • Sleep Therapy & Research Center
  • Comprehensive Sleep Medicine Associates
  • West Ottawa Sleep Centre
  • Toronto Sleep Institute
  • Jodha Tishon Inc.
  • Xuanwu Hospital Capital Medical University
  • The First Affiliated Hospital of Jinan University
  • The First Hospital of Jilin University
  • Huashan Hospital, Fudan University
  • Fakultni nemocnice Hradec Kralove
  • Fakultni nemocnice Ostrava
  • Vseobecna fakultni nemocnice v Praze
  • Terveystalo Helsinki Uniklinikka
  • Turku University Hospital
  • Hopital Gui de Chauliac
  • Hopital Roger Salengro - CHU Lille
  • SomnoCenter Budapest
  • IRCCS Oasi Maria SS
  • Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche
  • Ospedale San Raffaele (San Raffaele Turro)
  • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • SOUSEIKAI PS Clinic
  • You Ariyoshi Sleep Clinic
  • Kurume University Hospital
  • Kaiseikai Kita Shin Yokohama Internal Medicine Clinic
  • Howakai Kuwamizu Hospital
  • Jinyukai Kotorii Isahaya Hospital
  • Shunkaikai Inoue Hospital
  • Gokeikai Osaka Kaisei Hospital
  • Kyowakai Hannan Hospital
  • Koishikawa Tokyo Hospital
  • Nihon University Itabashi Hospital
  • Yoyogi Sleep Disorder Center
  • Sleep Support Clinic
  • Sleep & Stress Clinic
  • Sumida Hospital
  • The Catholic University of Korea, St. Vincent's Hospital
  • Keimyung University Dongsan Hospital
  • Stichting Epilepsie Instelling Nederland, Heemstede
  • Kempenhaeghe, Heeze
  • Hospital Universitario Araba Sede Santiago
  • Hospital General de Castellon
  • Hospital Clinic de Barcelona
  • Hospital Vithas Nuestra Senora de America

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Part A, Cohorts A1a and Cohorts A1b and A2 (Optional), NT1 Participants: Placebo

Part A, Cohort A1a, NT1 Participants: TAK-994 TBD

Part A, Cohort A1b, NT1 Participants: TAK-994

Part A, Cohort A2 (Optional), NT1 Participants: TAK-994 TBD

Part B, NT1 Participants: TAK-994 Dose 1

Part B, NT1 Participants: TAK-994 Dose 2

Part B, NT1 Participants: TAK-994 Dose 3

Part B, NT1 Participants: Placebo

Part C, NT1 Participants in China: Placebo

Part C, NT1 Participants in China: TAK-994

Part D, Cohort D1a, D1b and D2, NT2 Participants: Placebo

Part D, Cohort D1a, NT2 Participants: TAK-994

Part D, Cohort D1b, NT2 Participants: TAK-994

Part D, Cohort D2, NT2 Participants (Optional) : TAK-994 TBD

Arm Description

TAK-994 placebo-matching tablets for 28 days, in participants with NT1.

TAK-994, tablets, dose level 1 for 28 days, in participants with NT1.

TAK-994 tablets, dose to be determined (TBD) based on safety, tolerability and/or efficacy in Cohort A1a participants with NT1.

TAK-994 tablets, TBD based on safety, tolerability and/or efficacy data of Cohort A1, for 28 days.

TAK-994 dose 1, tablets, for 56 days in participants with NT1.

TAK-994 dose 2, tablets, for 56 days in participants with NT1.

TAK-994 dose 3, tablets, 56 days in participants with NT1.

TAK-994 placebo-matching tablets for 56 days in participants with NT1.

TAK-994 placebo-matching tablets for 56 days, in participants with NT1 in China.

TAK-994 tablets, dose TBD based on safety and tolerability in Part B, for 56 days in participants with NT1 in China.

TAK-994 placebo-matching tablets for 28 days, in participants with NT2.

TAK-994 tablets, dose TBD based on safety, tolerability and/or efficacy in Part A , for 28 days in participants with NT2.

TAK-994 tablets, dose TBD based on safety and/or tolerability efficacy in Cohort D1a participants with NT2.

TAK-994 tablets, TBD based on safety, tolerability and/or efficacy data of Cohort D1, for 28 days.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.

Secondary Outcome Measures

Parts A and D: Day 1, Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994
Parts A and D: Day 1, Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994
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
Parts A and D: Day 28, Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-994
Parts A and D: Day 28, Tmax: Time of First Occurrence of Cmax After Multiple Doses of TAK-994
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
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 18, 2019
Last Updated
March 27, 2023
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT04096560
Brief Title
A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
A safety signal has emerged in Phase 2 studies of TAK-994. As an immediate precautionary measure, Takeda has suspended dosing of patients and has decided to stop Phase 2 studies early.
Study Start Date
February 27, 2020 (Actual)
Primary Completion Date
November 5, 2021 (Actual)
Study Completion Date
November 5, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2)
Keywords
Drug therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
257 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A, Cohorts A1a and Cohorts A1b and A2 (Optional), NT1 Participants: Placebo
Arm Type
Placebo Comparator
Arm Description
TAK-994 placebo-matching tablets for 28 days, in participants with NT1.
Arm Title
Part A, Cohort A1a, NT1 Participants: TAK-994 TBD
Arm Type
Experimental
Arm Description
TAK-994, tablets, dose level 1 for 28 days, in participants with NT1.
Arm Title
Part A, Cohort A1b, NT1 Participants: TAK-994
Arm Type
Experimental
Arm Description
TAK-994 tablets, dose to be determined (TBD) based on safety, tolerability and/or efficacy in Cohort A1a participants with NT1.
Arm Title
Part A, Cohort A2 (Optional), NT1 Participants: TAK-994 TBD
Arm Type
Experimental
Arm Description
TAK-994 tablets, TBD based on safety, tolerability and/or efficacy data of Cohort A1, for 28 days.
Arm Title
Part B, NT1 Participants: TAK-994 Dose 1
Arm Type
Experimental
Arm Description
TAK-994 dose 1, tablets, for 56 days in participants with NT1.
Arm Title
Part B, NT1 Participants: TAK-994 Dose 2
Arm Type
Experimental
Arm Description
TAK-994 dose 2, tablets, for 56 days in participants with NT1.
Arm Title
Part B, NT1 Participants: TAK-994 Dose 3
Arm Type
Experimental
Arm Description
TAK-994 dose 3, tablets, 56 days in participants with NT1.
Arm Title
Part B, NT1 Participants: Placebo
Arm Type
Placebo Comparator
Arm Description
TAK-994 placebo-matching tablets for 56 days in participants with NT1.
Arm Title
Part C, NT1 Participants in China: Placebo
Arm Type
Placebo Comparator
Arm Description
TAK-994 placebo-matching tablets for 56 days, in participants with NT1 in China.
Arm Title
Part C, NT1 Participants in China: TAK-994
Arm Type
Experimental
Arm Description
TAK-994 tablets, dose TBD based on safety and tolerability in Part B, for 56 days in participants with NT1 in China.
Arm Title
Part D, Cohort D1a, D1b and D2, NT2 Participants: Placebo
Arm Type
Placebo Comparator
Arm Description
TAK-994 placebo-matching tablets for 28 days, in participants with NT2.
Arm Title
Part D, Cohort D1a, NT2 Participants: TAK-994
Arm Type
Experimental
Arm Description
TAK-994 tablets, dose TBD based on safety, tolerability and/or efficacy in Part A , for 28 days in participants with NT2.
Arm Title
Part D, Cohort D1b, NT2 Participants: TAK-994
Arm Type
Experimental
Arm Description
TAK-994 tablets, dose TBD based on safety and/or tolerability efficacy in Cohort D1a participants with NT2.
Arm Title
Part D, Cohort D2, NT2 Participants (Optional) : TAK-994 TBD
Arm Type
Experimental
Arm Description
TAK-994 tablets, TBD based on safety, tolerability and/or efficacy data of Cohort D1, for 28 days.
Intervention Type
Drug
Intervention Name(s)
TAK-994
Intervention Description
TAK-994 tablets.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
TAK-994 placebo-matching tablets.
Primary Outcome Measure Information:
Title
Parts A and D: Number of Participants who Experience at least 1 Treatment Emergent Adverse Events (TEAEs) During the Study
Description
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.
Time Frame
First dose of study treatment to end of study follow-up (up to Day 35)
Title
Parts A and D: Number of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at least Once Postdose During the Study
Description
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.
Time Frame
Baseline up to Day 35
Title
Parts A and D: Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at least Once Postdose During the Study
Description
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.
Time Frame
Baseline up to Day 35
Title
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
Description
A 12 lead ECG will be performed, the ECG values will be compared to pre-specified criteria for markedly abnormal values.
Time Frame
Baseline up to Day 35
Title
Parts B and C: Change From Baseline in Average Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT)
Description
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.
Time Frame
Baseline and Week 8 (Day 56)
Secondary Outcome Measure Information:
Title
Parts A and D: Day 1, Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994
Time Frame
Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Title
Parts A and D: Day 1, Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994
Time Frame
Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Title
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
Time Frame
Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Title
Parts A and D: Day 28, Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-994
Time Frame
Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Title
Parts A and D: Day 28, Tmax: Time of First Occurrence of Cmax After Multiple Doses of TAK-994
Time Frame
Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Title
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
Time Frame
Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose
Title
Parts B and C: Change From Baseline in Subjective Daytime Sleepiness as Assessed by ESS Score
Description
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.
Time Frame
Baseline and Week 8 (Day 56)
Title
Parts B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) as Reported in the Patient-Reported Sleep Diary
Description
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.
Time Frame
Baseline and Week 8 (Day 56)
Title
Parts B and C: Number of Participants who Experience at least 1 Treatment Emergent Adverse Events (TEAEs) During the Study
Description
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.
Time Frame
First dose of study treatment to end of study follow-up (Up to Day 63)
Title
Parts B and C: Number of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at least Once Postdose During the Study
Description
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.
Time Frame
Baseline up to Day 63
Title
Parts B and C: Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at least Once Postdose During the Study
Description
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.
Time Frame
Baseline up to Day 63
Title
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
Description
A 12 lead ECG will be performed, the ECG values will be compared to pre-specified criteria for markedly abnormal values.
Time Frame
Baseline up to Day 63
Title
Change from Baseline in Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT)
Description
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.
Time Frame
Baseline up to Week 4
Title
Change From Baseline in Subjective Daytime Sleepiness as Assessed by Epworth Sleepiness Scale (ESS) Score
Description
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.
Time Frame
Baseline up to Week 4
Title
Parts A, B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) as Reported in the Patient-Reported Sleep Diary
Description
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.
Time Frame
Baseline up to Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. The participant's Epworth Sleepiness Scale (ESS) score must be greater than or equal to (>=) 10 at Day -1. Must be willing to discontinue all medications used for the treatment of NT1/NT2. 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 . 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: 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. Is an excessive (>600 mg/day) caffeine user 1 week before to the study screening. 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. 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. 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. 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. Has a local infection at the puncture site. Has developed signs of lumbar radiculopathy, including lower extremity pain and paresthesia. Has any known focal neurological deficit that might suggest an increase in intracranial pressure.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Wright Clinical Research
City
Alabaster
State/Province
Alabama
ZIP/Postal Code
35007
Country
United States
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
CITrials - Bellflower
City
Bellflower
State/Province
California
ZIP/Postal Code
90706
Country
United States
Facility Name
Santa Monica Clinical Trials
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Stanford School of Medicine
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
Pacific Research Network, Inc
City
San Diego
State/Province
California
ZIP/Postal Code
92128
Country
United States
Facility Name
SDS Clinical Trials, Inc.
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Alpine Clinical Research Center
City
Boulder
State/Province
Colorado
ZIP/Postal Code
80301
Country
United States
Facility Name
Delta Waves Sleep Disorders and Research Center
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80918
Country
United States
Facility Name
St. Francis Medical Institute
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
Sleep Medicine Specialists of South Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
Country
United States
Facility Name
Clinical Trials of Florida
City
Miami
State/Province
Florida
ZIP/Postal Code
33186
Country
United States
Facility Name
JSV Clinical Research Study, Inc
City
Tampa
State/Province
Florida
ZIP/Postal Code
33624
Country
United States
Facility Name
Florida Pulmonary Research Institute, LLC
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32789
Country
United States
Facility Name
NeuroTrials Research, Inc.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30328
Country
United States
Facility Name
iResearch Atlanta, LLC
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
Sleep Practitioners, LLC
City
Macon
State/Province
Georgia
ZIP/Postal Code
31210
Country
United States
Facility Name
Global Research Associates
City
Stockbridge
State/Province
Georgia
ZIP/Postal Code
30281
Country
United States
Facility Name
Hawaii Pacific Neuroscience
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
Facility Name
Lutheran Sleep Disorder Center
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46804
Country
United States
Facility Name
University of Kansas Medical Center Research Institute, Inc.
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Neurocare, Inc., dba Neurocare Center for Research
City
Newton
State/Province
Massachusetts
ZIP/Postal Code
02459
Country
United States
Facility Name
Research Carolina Elite LLC
City
Denver
State/Province
North Carolina
ZIP/Postal Code
28037
Country
United States
Facility Name
Clinical Research of Gastonia
City
Gastonia
State/Province
North Carolina
ZIP/Postal Code
28054
Country
United States
Facility Name
Raleigh Neurology Associates
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
CTI Clinical Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45245
Country
United States
Facility Name
Intrepid Research
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45245
Country
United States
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio Sleep Medicine and Neuroscience Institute
City
Dublin
State/Province
Ohio
ZIP/Postal Code
43017
Country
United States
Facility Name
Respiratory Specialists
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Medical University of South Carolina (MUSC)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Bogan Sleep Consultants, LLC
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29201
Country
United States
Facility Name
Sleep Therapy & Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Comprehensive Sleep Medicine Associates
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77478
Country
United States
Facility Name
West Ottawa Sleep Centre
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K2A3Z8
Country
Canada
Facility Name
Toronto Sleep Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4P 1P2
Country
Canada
Facility Name
Jodha Tishon Inc.
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5S 3A3
Country
Canada
Facility Name
Xuanwu Hospital Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100053
Country
China
Facility Name
The First Affiliated Hospital of Jinan University
City
Tianhe
State/Province
Guangdong
ZIP/Postal Code
510630
Country
China
Facility Name
The First Hospital of Jilin University
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Huashan Hospital, Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
50333
Country
Czechia
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha 2
ZIP/Postal Code
128 21
Country
Czechia
Facility Name
Terveystalo Helsinki Uniklinikka
City
Helsinki
ZIP/Postal Code
380
Country
Finland
Facility Name
Turku University Hospital
City
Turku
ZIP/Postal Code
20521
Country
Finland
Facility Name
Hopital Gui de Chauliac
City
Montpellier
State/Province
Herault
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Roger Salengro - CHU Lille
City
Lille
State/Province
Nord
ZIP/Postal Code
59037
Country
France
Facility Name
SomnoCenter Budapest
City
Budapest
ZIP/Postal Code
1012
Country
Hungary
Facility Name
IRCCS Oasi Maria SS
City
Troina
State/Province
Enna
ZIP/Postal Code
94018
Country
Italy
Facility Name
Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche
City
Bologna
ZIP/Postal Code
40123
Country
Italy
Facility Name
Ospedale San Raffaele (San Raffaele Turro)
City
Milano
ZIP/Postal Code
20127
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
City
Roma
ZIP/Postal Code
133
Country
Italy
Facility Name
SOUSEIKAI PS Clinic
City
Fukuoka-shi
State/Province
Fukuoka-Ken
ZIP/Postal Code
812-0025
Country
Japan
Facility Name
You Ariyoshi Sleep Clinic
City
Kitakyushu-shi
State/Province
Fukuoka-Ken
ZIP/Postal Code
802-0084
Country
Japan
Facility Name
Kurume University Hospital
City
Kurume-shi
State/Province
Fukuoka-Ken
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
Kaiseikai Kita Shin Yokohama Internal Medicine Clinic
City
Yokohama-shi
State/Province
Kanagawa-Ken
ZIP/Postal Code
223-0059
Country
Japan
Facility Name
Howakai Kuwamizu Hospital
City
Kumamoto-shi
State/Province
Kumamoto-Ken
ZIP/Postal Code
862-0954
Country
Japan
Facility Name
Jinyukai Kotorii Isahaya Hospital
City
Isahaya-shi
State/Province
Nagasaki-Ken
ZIP/Postal Code
854-0081
Country
Japan
Facility Name
Shunkaikai Inoue Hospital
City
Nagasaki-shi
State/Province
Nagasaki-Ken
ZIP/Postal Code
850-0045
Country
Japan
Facility Name
Gokeikai Osaka Kaisei Hospital
City
Osaka-shi
State/Province
Osaka-Fu
ZIP/Postal Code
532-0003
Country
Japan
Facility Name
Kyowakai Hannan Hospital
City
Sakai-shi
State/Province
Osaka-Fu
ZIP/Postal Code
599-8263
Country
Japan
Facility Name
Koishikawa Tokyo Hospital
City
Bunkyo-ku
State/Province
Tokyo-To
ZIP/Postal Code
112-0012
Country
Japan
Facility Name
Nihon University Itabashi Hospital
City
Itabashi-ku
State/Province
Tokyo-To
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Yoyogi Sleep Disorder Center
City
Shibuya-ku
State/Province
Tokyo-To
ZIP/Postal Code
151-0053
Country
Japan
Facility Name
Sleep Support Clinic
City
Shinagawa-ku
State/Province
Tokyo-To
ZIP/Postal Code
140-0011
Country
Japan
Facility Name
Sleep & Stress Clinic
City
Shinagawa-ku
State/Province
Tokyo-To
ZIP/Postal Code
141-6003
Country
Japan
Facility Name
Sumida Hospital
City
Sumida-ku
State/Province
Tokyo-To
ZIP/Postal Code
130-0004
Country
Japan
Facility Name
The Catholic University of Korea, St. Vincent's Hospital
City
Suwon-si
State/Province
Gyeonggi-do
ZIP/Postal Code
16247
Country
Korea, Republic of
Facility Name
Keimyung University Dongsan Hospital
City
Daegu
ZIP/Postal Code
42601
Country
Korea, Republic of
Facility Name
Stichting Epilepsie Instelling Nederland, Heemstede
City
Heemstede
ZIP/Postal Code
2103 SW
Country
Netherlands
Facility Name
Kempenhaeghe, Heeze
City
Heeze
ZIP/Postal Code
5591 VE
Country
Netherlands
Facility Name
Hospital Universitario Araba Sede Santiago
City
Vitoria
State/Province
Alava
ZIP/Postal Code
1004
Country
Spain
Facility Name
Hospital General de Castellon
City
Castellon de la Plana
State/Province
Castellon
ZIP/Postal Code
12004
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Hospital Vithas Nuestra Senora de America
City
Madrid
ZIP/Postal Code
28043
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/5f6b603c4db2bf003ab4a34e
Description
: To obtain more information on the study, click here/on this link

Learn more about this trial

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

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