A Study of TAK-994 in Adults With Type 1 and Type 2 Narco... | NCT04096560 | Trialant
NCT04096560
Sponsor
Takeda
Status
Terminated
Last Update Posted
Oct 29, 2024Actual
Enrollment
97Actual
Phase
Phase 2
Conditions
Narcolepsy Type 1 (NT1)
Narcolepsy Type 2 (NT2)
Interventions
TAK-994
Placebo
Countries
United States
Canada
China
Czechia
Finland
France
Hungary
Italy
Japan
Netherlands
South Korea
Spain
Protocol Section
Identification Module
NCT ID
NCT04096560
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
TAK-994-1501
Secondary IDs
ID
Type
Description
Link
JapicCTI-205178
Registry Identifier
JapicCTI
2020-000777-24
Registry Identifier
EudraCT
U1111-1240-0346
Registry Identifier
WHO
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)
Acronym
Not provided
Organization
TakedaINDUSTRY
Status Module
Record Verification Date
Oct 2024
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
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.
Expanded Access Info
No
Start Date
May 27, 2020Actual
Primary Completion Date
Nov 5, 2021Actual
Completion Date
Nov 5, 2021Actual
First Submitted Date
Sep 18, 2019
First Submission Date that Met QC Criteria
Sep 18, 2019
First Posted Date
Sep 20, 2019Actual
Results Waived
Not provided
Results First Submitted Date
Oct 4, 2024
Results First Submitted that Met QC Criteria
Oct 4, 2024
Results First Posted Date
Oct 29, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Oct 5, 2022
Certification/Extension First Submitted that Passed QC Review
Oct 5, 2022
Certification/Extension First Posted Date
Oct 10, 2022Actual
Last Update Submitted Date
Oct 4, 2024
Last Update Posted Date
Oct 29, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
TakedaINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Not provided
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Narcolepsy Type 1 (NT1)
Narcolepsy Type 2 (NT2)
Keywords
Drug therapy
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
97Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A: Placebo
Placebo Comparator
TAK-994 placebo-matching tablets, orally, twice daily (BID) for 28 days, in participants with NT1.
Drug: Placebo
Part A: TAK-994 120 mg
Experimental
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
Drug: TAK-994
Part A: TAK-994 180 mg
Experimental
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Drug: TAK-994
Part B: Placebo
Placebo Comparator
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
Drug: Placebo
Part B: TAK-994 30 mg
Experimental
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
Drug: TAK-994
Part B: TAK-994 90 mg
Experimental
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
TAK-994
Drug
TAK-994 tablets.
Part A: TAK-994 120 mg
Part A: TAK-994 180 mg
Part B: TAK-994 180 mg
Part B: TAK-994 30 mg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part A: Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) 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) in Part A
Part A: Number of Participants Who Meet the Markedly Abnormal Value Criteria for Safety Laboratory Tests at Least Once Postdose During the Study
Standard safety laboratory values (hematology, serum chemistry, urinalysis) were collected and compared to pre-specified criteria for markedly abnormal values. Markedly abnormal values criteria: Erythrocytes(10^12/L:<0.8xlower limit of normal(LLN), >1.2xupper limit of normal(ULN); Hemoglobin grams per litre(g/L):<0.8xLLN, >1.2xULN; Hematocrit voltage/volts(V/V):<0.8xLLN, >1.2xULN; Platelets(10^9/L):<75, >600; Leukocytes(10^9/L):<0.5xLLN, >1.5xULN; Alanine Aminotransferase units/litre(U/L):>3xULN, Aspartate Aminotransferase(U/L):>3xULN; Bilirubin micromoles/litre (umol/L):>1.5xULN; Alkaline Phosphatase(U/L):>3xULN; Gamma Glutamyl Transferase(U/L):>3 x ULN; Albumin(g/L):<25; Protein Total(g/L):<0.8xLLN, >1.2xULN;Glucose millimoles/litre(mmol/L):<2.8, >19.4; Calcium(mmol/L):<1.92, >2.77; Creatinine(umol/L):>1.5xULN; Urea(mmol/L):>10.7; Sodium(mmol/L):<130, >150; Potassium(mmol/L):<3.0, >5.3. Only categories with at least one participant with event are reported.
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
Part A: Number of Participants Who Meet the Markedly Abnormal Value Criteria for Vital Sign Measurements at Least Once Postdose During the Study
Vital signs (body temperature and sitting blood pressure) were collected and compared to pre-specified criteria for markedly abnormal values throughout the study. Markedly abnormal values criteria: Heart Rate (beats/min): <40, >115; Systolic Blood Pressure millimeters of mercury (mmHg): <90, ≥160, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Diastolic Blood Pressure (mmHg): <50, ≥100, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Respiratory Rate (breaths/min): >21; Temperature Celsius (C): >38.5. Only categories with at least one participant with event are reported.
Secondary Outcomes
Measure
Description
Time Frame
Part A: Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994 at Day 1
Pre-dose and at multiple time points (up to 14 hours) post-dose at Day 1 in Part A
Part A: Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994 at Day 1
Other Outcomes
Not provided
Eligibility Module
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.
Dauvilliers Y, Mignot E, Del Rio Villegas R, Du Y, Hanson E, Inoue Y, Kadali H, Koundourakis E, Meyer S, Rogers R, Scammell TE, Sheikh SI, Swick T, Szakacs Z, von Rosenstiel P, Wu J, Zeitz H, Murthy NV, Plazzi G, von Hehn C. Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1. N Engl J Med. 2023 Jul 27;389(4):309-321. doi: 10.1056/NEJMoa2301940.
See Also Links
Label
URL
: To obtain more information on the study, click here/on this link
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.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame
Not provided
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.
Participants with Narcolepsy Type 1 or Type 2 were planned to be enrolled in study in Parts A, B, C and D to receive TAK-994 or placebo. Due to the early termination of the study, data was not collected for Part C: placebo and was insufficient for Part C: TAK-994 180 mg to allow the pre-planned analyses. Similarly, for Part D, the prespecified sample size at Week 4 was not reached and therefore the pre-planned analyses cannot be adequately interpreted.
Recruitment Details
Participants took part in the study at 35 investigative sites in Canada, China, France, Hungary, Italy, Japan, South Korea, Spain and United States from 27 May 2020 to 05 November 2021. The study was early terminated due to a safety signal that had emerged in the phase 2 studies of firazorexton.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, twice daily (BID) for 28 days, in participants with NT1.
FG001
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
Drug: TAK-994
Part C: TAK-994 180 mg
Experimental
TAK-994 180 mg tablets, orally, BID for 56 days, in Chinese participants with NT1.
Drug: TAK-994
Part B: TAK-994 90 mg
Part C: TAK-994 180 mg
Firazorexton
Placebo
Drug
TAK-994 placebo-matching tablets.
Part A: Placebo
Part B: Placebo
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
Part A: Number of Participants Who Meet the Markedly Abnormal Value Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose During the Study
A 12 lead ECG was performed, the ECG values were compared to pre-specified criteria for markedly abnormal values. Markedly abnormal values criteria: ECG Mean Heart Rate (beats/min): <40, >115; PR Interval milliseconds (msec): ≤80, ≥200; corrected QT interval by Fredericia (QTcF) Interval (msec): ≤300, >500, ≥30 change from baseline and >450; QRS Duration (msec): ≤80, ≥180. Only categories with at least one participant with event are reported.
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
Parts B and C: Change From Baseline in Average Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT)
MWT: validated, objective measure that evaluates person's ability to remain awake under soporific conditions for defined period. During each MWT session (1 session=40 minutes), participants were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on electroencephalography (EEG). If no sleep had been observed according to these rules, then latency= 40 minutes. Mixed-effect model for repeated measures (MMRM) was used for analysis. Due to early termination of the study, no post-baseline efficacy data for this outcome measure was collected and analyzed for participants in Part C: TAK-994 180 mg.
Baseline and Week 8 (Day 56) in Parts B and C
Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 1 in Part A
Part A: 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 at Day 1
Pre-dose and at multiple time points (up to 24 hours) post-dose at Day 1 in Part A
Part A: Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-994 at Day 28
Pre-dose and at multiple time points (up to 14 hours) post-dose at Day 28 in Part A
Part A: Tmax: Time of First Occurrence of Cmax After Multiple Doses of TAK-994 at Day 28
Pre-dose and at multiple time points (up to 14 hours) post-dose at Day 28 in Part A
Part A: AUC(0-t): Area Under the Concentration-time Curve From Time 0 to Time Tau Over a Dosing Interval of TAK-994 at Day 28
Pre-dose and at multiple time points (Up to 12 hours) post-dose at Day 28 in Part A
Parts B and C: Change From Baseline in the Epworth Sleepiness Scale (ESS) Total Score to Week 8
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 participants 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. MMRM was used for analysis. Due to early termination of the study, no post-baseline secondary efficacy data for this outcome measure was collected and analyzed for participants in Part C: TAK-994 180 mg.
Baseline and Week 8 (Day 56) in Parts B and C
Parts B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) at Week 8
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. WCR = (Total number of cataplexy over a number of non-missing diary days for a given duration/number of Non-missing diary days in that duration)*7. MMRM was used for the analysis. Due to early termination of the study, no secondary efficacy data was collected and analyzed for participants in Part C: TAK-994 180 mg.
Baseline and Week 8 (Day 56) in Parts B and C
Parts B and C: Number of Participants Who Experience at Least 1 TEAE During the Study
An 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 drug to end of study follow-up (up to Day 63) in Parts B and C
Parts B and C: Number of Participants Who Met the Markedly Abnormal Value Criteria for Safety Laboratory Tests at Least Once Postdose During the Study
Standard safety laboratory values (serum chemistry, hematology, and urine analysis) were collected and compared to pre-specified criteria for Markedly Abnormal Values throughout the study. Markedly abnormal values criteria: Alanine Aminotransferase (U/L):>3xULN, Aspartate Aminotransferase(U/L):>3xULN; Bilirubin micromoles/litre (umol/L):>1.5xULN; Calcium(mmol/L):<1.92, >2.77; Potassium(mmol/L):<3.0, >5.3. Only categories with at least one participant with event are reported.
Up to Day 63 in Parts B and C
Parts B and C: Number of Participants Who Met the Markedly Abnormal Value Criteria for Vital Sign Measurements at Least Once Postdose During the Study
Vital signs (body temperature and sitting blood pressure) were collected and compared to pre-specified criteria for markedly abnormal values throughout the study. Markedly abnormal values criteria: Systolic Blood Pressure millimeters of mercury (mmHg): <90, ≥160, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Diastolic Blood Pressure (mmHg): <50, ≥100, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Respiratory Rate (breaths/min): >21.Only categories with at least one participant with event are reported.
Up to Day 63 in Parts B and C
Parts B and C: Number of Participants Who Met the Markedly Abnormal Value Criteria for ECG Parameters at Least Once Postdose During the Study
A 12 lead ECG was performed, the ECG values were compared to pre-specified criteria for markedly abnormal values. Markedly abnormal values criteria: PR Interval (msec): ≤80, ≥200; QRS Duration (msec): ≤80, ≥180. Only categories with at least one participant with event are reported.
Up to Day 63 in Parts B and C
Phoenix
Arizona
85054
United States
CITrials - Bellflower
Bellflower
California
90706
United States
Santa Monica Clinical Trials
Los Angeles
California
90025
United States
Stanford School of Medicine
Redwood City
California
94063
United States
Pacific Research Network, Inc
San Diego
California
92128
United States
SDS Clinical Trials, Inc.
Santa Ana
California
92705
United States
Alpine Clinical Research Center
Boulder
Colorado
80301
United States
Delta Waves Sleep Disorders and Research Center
Colorado Springs
Colorado
80918
United States
St. Francis Medical Institute
Clearwater
Florida
33765
United States
Sleep Medicine Specialists of South Florida
Miami
Florida
33126
United States
Clinical Trials of Florida
Miami
Florida
33186
United States
JSV Clinical Research Study, Inc
Tampa
Florida
33624
United States
Florida Pulmonary Research Institute, LLC
Winter Park
Florida
32789
United States
NeuroTrials Research, Inc.
Atlanta
Georgia
30328
United States
iResearch Atlanta, LLC
Decatur
Georgia
30030
United States
Sleep Practitioners, LLC
Macon
Georgia
31210
United States
Global Research Associates
Stockbridge
Georgia
30281
United States
Hawaii Pacific Neuroscience
Honolulu
Hawaii
96817
United States
Lutheran Sleep Disorder Center
Fort Wayne
Indiana
46804
United States
University of Kansas Medical Center Research Institute, Inc.
Kansas City
Kansas
66160
United States
Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"
Chevy Chase
Maryland
20815
United States
Boston Children's Hospital
Boston
Massachusetts
02115
United States
Neurocare, Inc., dba Neurocare Center for Research
Newton
Massachusetts
02459
United States
Research Carolina Elite LLC
Denver
North Carolina
28037
United States
Clinical Research of Gastonia
Gastonia
North Carolina
28054
United States
Raleigh Neurology Associates
Raleigh
North Carolina
27607
United States
CTI Clinical Research Center
Cincinnati
Ohio
45245
United States
Intrepid Research
Cincinnati
Ohio
45245
United States
The Cleveland Clinic Foundation
Cleveland
Ohio
44195
United States
Ohio Sleep Medicine and Neuroscience Institute
Dublin
Ohio
43017
United States
Respiratory Specialists
Wyomissing
Pennsylvania
19610
United States
Medical University of South Carolina (MUSC)
Charleston
South Carolina
29425
United States
Bogan Sleep Consultants, LLC
Columbia
South Carolina
29201
United States
Sleep Therapy & Research Center
San Antonio
Texas
78229
United States
Comprehensive Sleep Medicine Associates
Sugar Land
Texas
77478
United States
West Ottawa Sleep Centre
Ottawa
Ontario
K2A3Z8
Canada
Toronto Sleep Institute
Toronto
Ontario
M4P 1P2
Canada
Jodha Tishon Inc.
Toronto
Ontario
M5S 3A3
Canada
Xuanwu Hospital Capital Medical University
Beijing
Beijing Municipality
100053
China
The First Affiliated Hospital of Jinan University
Tianhe
Guangdong
510630
China
The First Hospital of Jilin University
Changchun
Jilin
130021
China
Huashan Hospital, Fudan University
Shanghai
Shanghai Municipality
200040
China
Fakultni nemocnice Hradec Kralove
Hradec Králové
50333
Czechia
Fakultni nemocnice Ostrava
Ostrava
708 52
Czechia
Vseobecna fakultni nemocnice v Praze
Prague
128 21
Czechia
Terveystalo Helsinki Uniklinikka
Helsinki
380
Finland
Turku University Hospital
Turku
20521
Finland
Hopital Gui de Chauliac
Montpellier
Herault
34295
France
Hopital Roger Salengro - CHU Lille
Lille
Nord
59037
France
SomnoCenter Budapest
Budapest
1012
Hungary
IRCCS Oasi Maria SS
Troina
Enna
94018
Italy
Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche
Bologna
40123
Italy
Ospedale San Raffaele (San Raffaele Turro)
Milan
20127
Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma
133
Italy
SOUSEIKAI PS Clinic
Fukuoka
Fukuoka
812-0025
Japan
You Ariyoshi Sleep Clinic
Kitakyushu-shi
Fukuoka
802-0084
Japan
Kurume University Hospital
Kurume-shi
Fukuoka
830-0011
Japan
Kaiseikai Kita Shin Yokohama Internal Medicine Clinic
The Catholic University of Korea, St. Vincent's Hospital
Suwon
Gyeonggi-do
16247
South Korea
Keimyung University Dongsan Hospital
Daegu
42601
South Korea
Hospital Universitario Araba Sede Santiago
Vitoria-Gasteiz
Alava
1004
Spain
Hospital General de Castellon
Castellon
Castellon
12004
Spain
Hospital Clinic de Barcelona
Barcelona
8036
Spain
Hospital Vithas Nuestra Senora de America
Madrid
28043
Spain
FG002
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
FG003
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
FG004
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
FG005
Part B: TAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
FG006
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
FG007
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in Chinese participants with NT1.
FG0007 subjects
FG0017 subjects
FG0028 subjects
FG00317 subjects
FG00417 subjects
FG00520 subjects
FG00619 subjects
FG0072 subjects
COMPLETED
FG0006 subjects
FG0017 subjects
FG0028 subjects
FG00312 subjects
FG00410 subjects
FG00512 subjects
FG0069 subjects
FG0070 subjects
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0035 subjects
FG0047 subjects
FG0058 subjects
FG00610 subjects
FG0072 subjects
Type
Comment
Reasons
Reason not Specified
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0051 subjects
FG0061 subjects
FG0070 subjects
Pretreatment Event, Serious Adverse Event, or Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Study Terminated by Sponsor
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0035 subjects
FG004
Met the Discontinuation Criteria of the Protocol
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, BID for 28 days, in participants with NT1.
BG001
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
BG002
Part A: TAK-994 180 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1
BG003
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
BG004
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
BG005
Part B: TAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
BG006
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
BG007
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in Chinese participants with NT1.
BG008
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0007
BG0017
BG0028
BG00317
BG00417
BG00520
BG00619
BG0072
BG00897
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Full Range
years
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG0028
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Height
Mean
Full Range
centimeters (cm)
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Weight
Mean
Full Range
kilograms (kg)
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Body Mass Index (BMI)
BMI= Weight (kg)/[height(m)^2]
Mean
Full Range
kilogram per square meter (kg/m^2)
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Average Sleep Latency (MWT)
The Maintenance of Wakefulness Test (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 were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on electroencephalography (EEG). If no sleep was observed according to these rules, then the latency was defined as 40 minutes.
Mean
Full Range
minutes
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
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.
Mean
Full Range
score on a scale
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
Participants
Weekly Cataplexy Rate (WCR)
WCR = (Total number of cataplexy over a number of non-missing diary days for a given duration/number of Non-missing diary days in that duration)*7.
Due to early termination of the study, no secondary efficacy data was collected and analyzed for participants in Part C: TAK-994 180 mg.
Mean
Full Range
cataplexy attacks per week
Title
Denominators
Categories
ParticipantsBG0007
ParticipantsBG0017
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part A: Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) 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.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
ID
Title
Description
OG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG002
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG0007
OG0017
OG0028
Title
Denominators
Categories
Title
Measurements
OG0002
OG0016
OG0027
Primary
Part A: Number of Participants Who Meet the Markedly Abnormal Value Criteria for Safety Laboratory Tests at Least Once Postdose During the Study
Standard safety laboratory values (hematology, serum chemistry, urinalysis) were collected and compared to pre-specified criteria for markedly abnormal values. Markedly abnormal values criteria: Erythrocytes(10^12/L:<0.8xlower limit of normal(LLN), >1.2xupper limit of normal(ULN); Hemoglobin grams per litre(g/L):<0.8xLLN, >1.2xULN; Hematocrit voltage/volts(V/V):<0.8xLLN, >1.2xULN; Platelets(10^9/L):<75, >600; Leukocytes(10^9/L):<0.5xLLN, >1.5xULN; Alanine Aminotransferase units/litre(U/L):>3xULN, Aspartate Aminotransferase(U/L):>3xULN; Bilirubin micromoles/litre (umol/L):>1.5xULN; Alkaline Phosphatase(U/L):>3xULN; Gamma Glutamyl Transferase(U/L):>3 x ULN; Albumin(g/L):<25; Protein Total(g/L):<0.8xLLN, >1.2xULN;Glucose millimoles/litre(mmol/L):<2.8, >19.4; Calcium(mmol/L):<1.92, >2.77; Creatinine(umol/L):>1.5xULN; Urea(mmol/L):>10.7; Sodium(mmol/L):<130, >150; Potassium(mmol/L):<3.0, >5.3. Only categories with at least one participant with event are reported.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
ID
Title
Description
OG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 120 mg
Primary
Part A: Number of Participants Who Meet the Markedly Abnormal Value Criteria for Vital Sign Measurements at Least Once Postdose During the Study
Vital signs (body temperature and sitting blood pressure) were collected and compared to pre-specified criteria for markedly abnormal values throughout the study. Markedly abnormal values criteria: Heart Rate (beats/min): <40, >115; Systolic Blood Pressure millimeters of mercury (mmHg): <90, ≥160, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Diastolic Blood Pressure (mmHg): <50, ≥100, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Respiratory Rate (breaths/min): >21; Temperature Celsius (C): >38.5. Only categories with at least one participant with event are reported.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
ID
Title
Description
OG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
Primary
Part A: Number of Participants Who Meet the Markedly Abnormal Value Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose During the Study
A 12 lead ECG was performed, the ECG values were compared to pre-specified criteria for markedly abnormal values. Markedly abnormal values criteria: ECG Mean Heart Rate (beats/min): <40, >115; PR Interval milliseconds (msec): ≤80, ≥200; corrected QT interval by Fredericia (QTcF) Interval (msec): ≤300, >500, ≥30 change from baseline and >450; QRS Duration (msec): ≤80, ≥180. Only categories with at least one participant with event are reported.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
Posted
Count of Participants
Participants
First dose of study treatment to end of study follow-up (up to Day 35) in Part A
ID
Title
Description
OG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG002
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Primary
Parts B and C: Change From Baseline in Average Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT)
MWT: validated, objective measure that evaluates person's ability to remain awake under soporific conditions for defined period. During each MWT session (1 session=40 minutes), participants were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on electroencephalography (EEG). If no sleep had been observed according to these rules, then latency= 40 minutes. Mixed-effect model for repeated measures (MMRM) was used for analysis. Due to early termination of the study, no post-baseline efficacy data for this outcome measure was collected and analyzed for participants in Part C: TAK-994 180 mg.
Full Analysis Set included participants who received at least 1 dose of study drug, had baseline measure and at least 1 evaluable post-dose value. Overall number of participants analyzed is the number of participants available for analyses.
Posted
Least Squares Mean
Standard Error
minutes (min)
Baseline and Week 8 (Day 56) in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Secondary
Part A: Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994 at Day 1
Pharmacokinetic (PK) Analysis Set included all participants who received at least 1 dose of TAK-994 and had at least 1 measurable plasma concentration. Overall number of participants analyzed is the number of participants available for analyses.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter (ng/mL)
Pre-dose and at multiple time points (up to 14 hours) post-dose at Day 1 in Part A
ID
Title
Description
OG000
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG000
Secondary
Part A: Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994 at Day 1
PK Analysis Set included all participants who received at least 1 dose of TAK-994 and had at least 1 measurable plasma concentration. Overall number of participants analyzed is the number of participants available for analyses.
Posted
Median
Full Range
hours (h)
Pre-dose and at multiple time points (Up to 14 hours) post-dose at Day 1 in Part A
ID
Title
Description
OG000
Part A: TAK-994 120 mg
TAK-994 120 mg tablets, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG000
Secondary
Part A: 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 at Day 1
PK Analysis Set included all participants who received at least 1 dose of TAK-994 and had at least 1 measurable plasma concentration. Overall number analyzed is the number of participants with data available for analyses.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms*hour per milliliter (ng*h/mL)
Pre-dose and at multiple time points (up to 24 hours) post-dose at Day 1 in Part A
ID
Title
Description
OG000
Part A: TAK-994 120 mg
TAK-994 120 mg tablets, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG000
Secondary
Part A: Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-994 at Day 28
PK Analysis Set included all participants who received at least 1 dose of TAK-994 and had at least 1 measurable plasma concentration.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose and at multiple time points (up to 14 hours) post-dose at Day 28 in Part A
ID
Title
Description
OG000
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG000
Secondary
Part A: Tmax: Time of First Occurrence of Cmax After Multiple Doses of TAK-994 at Day 28
PK Analysis Set included all participants who received at least 1 dose of TAK-994 and had at least 1 measurable plasma concentration.
Posted
Median
Full Range
hours (h)
Pre-dose and at multiple time points (up to 14 hours) post-dose at Day 28 in Part A
ID
Title
Description
OG000
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG000
Secondary
Part A: AUC(0-t): Area Under the Concentration-time Curve From Time 0 to Time Tau Over a Dosing Interval of TAK-994 at Day 28
PK Analysis Set included all participants who received at least 1 dose of TAK-994 and had at least 1 measurable plasma concentration.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Pre-dose and at multiple time points (Up to 12 hours) post-dose at Day 28 in Part A
ID
Title
Description
OG000
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG001
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG000
Secondary
Parts B and C: Change From Baseline in the Epworth Sleepiness Scale (ESS) Total Score to Week 8
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 participants 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. MMRM was used for analysis. Due to early termination of the study, no post-baseline secondary efficacy data for this outcome measure was collected and analyzed for participants in Part C: TAK-994 180 mg.
Full Analysis Set included participants who received at least 1 dose of study drug, had baseline measure and at least 1 evaluable post-dose value. Overall number of participants analyzed is the number of participants available for analyses.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline and Week 8 (Day 56) in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Part B: TAK-994 90 mg
Secondary
Parts B and C: Change From Baseline in Weekly Cataplexy Rate (WCR) at Week 8
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. WCR = (Total number of cataplexy over a number of non-missing diary days for a given duration/number of Non-missing diary days in that duration)*7. MMRM was used for the analysis. Due to early termination of the study, no secondary efficacy data was collected and analyzed for participants in Part C: TAK-994 180 mg.
Full Analysis Set included participants who received at least 1 dose of study drug, had baseline measure and at least 1 evaluable post-dose value. Overall number of participants analyzed is the number of participants available for analyses.
Posted
Mean
Standard Deviation
cataplexy attacks per week
Baseline and Week 8 (Day 56) in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Part B: TAK-994 90 mg
Secondary
Parts B and C: Number of Participants Who Experience at Least 1 TEAE During the Study
An 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.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of the study drug.
Posted
Count of Participants
Participants
First dose of study drug to end of study follow-up (up to Day 63) in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Part B: FTAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
Secondary
Parts B and C: Number of Participants Who Met the Markedly Abnormal Value Criteria for Safety Laboratory Tests at Least Once Postdose During the Study
Standard safety laboratory values (serum chemistry, hematology, and urine analysis) were collected and compared to pre-specified criteria for Markedly Abnormal Values throughout the study. Markedly abnormal values criteria: Alanine Aminotransferase (U/L):>3xULN, Aspartate Aminotransferase(U/L):>3xULN; Bilirubin micromoles/litre (umol/L):>1.5xULN; Calcium(mmol/L):<1.92, >2.77; Potassium(mmol/L):<3.0, >5.3. Only categories with at least one participant with event are reported.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of the study drug.
Posted
Count of Participants
Participants
Up to Day 63 in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Part B: TAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
Secondary
Parts B and C: Number of Participants Who Met the Markedly Abnormal Value Criteria for Vital Sign Measurements at Least Once Postdose During the Study
Vital signs (body temperature and sitting blood pressure) were collected and compared to pre-specified criteria for markedly abnormal values throughout the study. Markedly abnormal values criteria: Systolic Blood Pressure millimeters of mercury (mmHg): <90, ≥160, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Diastolic Blood Pressure (mmHg): <50, ≥100, Change from Pre-Dose >20, Change from Pre-Dose >30, Time-matched Change from Baseline > 20, Time-matched Change from Baseline > 30; Respiratory Rate (breaths/min): >21.Only categories with at least one participant with event are reported.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of the study drug.
Posted
Count of Participants
Participants
Up to Day 63 in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Part B: TAK-994 90 mg
Secondary
Parts B and C: Number of Participants Who Met the Markedly Abnormal Value Criteria for ECG Parameters at Least Once Postdose During the Study
A 12 lead ECG was performed, the ECG values were compared to pre-specified criteria for markedly abnormal values. Markedly abnormal values criteria: PR Interval (msec): ≤80, ≥200; QRS Duration (msec): ≤80, ≥180. Only categories with at least one participant with event are reported.
Safety Analysis Set included all participants who were randomized and received at least 1 dose of the study drug.
Posted
Count of Participants
Participants
Up to Day 63 in Parts B and C
ID
Title
Description
OG000
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
OG001
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
OG002
Part B: TAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
OG003
Part B: TAK-994 180 mg
Time Frame
First dose of study treatment to end of study follow-up (up to Day 35 in Part A and up to Day 63 in Parts B and C)
Description
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: Placebo
TAK-994 placebo-matching tablets, orally, BID for 28 days, in participants with NT1.
0
7
0
7
2
7
EG001
Part A: TAK-994 120 mg
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
0
7
0
7
6
7
EG002
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
0
8
0
8
7
8
EG003
Part B: Placebo
TAK-994 placebo-matching tablets, orally, BID for 56 days, in participants with NT1.
0
17
0
17
4
17
EG004
Part B: TAK-994 30 mg
TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.
0
17
0
17
13
17
EG005
Part B: TAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
0
20
0
20
17
20
EG006
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
0
19
1
19
14
19
EG007
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1
0
2
0
2
2
2
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hepatitis acute
Hepatobiliary disorders
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG0030 affected17 at risk
EG0040 affected17 at risk
EG0050 affected20 at risk
EG0061 affected19 at risk
EG0070 affected2 at risk
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal mass
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG0030 affected17 at risk
EG0041 affected17 at risk
EG0050 affected20 at risk
EG0060 affected19 at risk
EG0070 affected2 at risk
Abdominal pain upper
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Acute sinusitis
Infections and infestations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Agitation
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0021 affected8 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Blepharospasm
Eye disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Blood pressure increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0021 affected8 at risk
EG003
Blood urea increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0021 affected8 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0021 affected8 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Ex-tobacco user
Social circumstances
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Faeces hard
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Fatigue
General disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Feeling jittery
General disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Giardiasis
Infections and infestations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Glutamate dehydrogenase increased
Investigations
MedDRA 24
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Granulocytopenia
Blood and lymphatic system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Headache
Nervous system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Heart rate increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Hepatic enzyme increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 24
Systematic Assessment
EG0001 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Hypertension
Vascular disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Hypertonic bladder
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Hypervigilance
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Increased appetite
Metabolism and nutrition disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Initial insomnia
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0022 affected8 at risk
EG003
Micturition urgency
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0022 affected8 at risk
EG003
Middle insomnia
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Papule
Skin and subcutaneous tissue disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0013 affected7 at risk
EG0025 affected8 at risk
EG003
Polyuria
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Puncture site erythema
General disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Pyrexia
General disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Rotator cuff syndrome
Musculoskeletal and connective tissue disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0021 affected8 at risk
EG003
Salivary hypersecretion
Gastrointestinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0023 affected8 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Skin laceration
Injury, poisoning and procedural complications
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Sleep disorder
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Tension headache
Nervous system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Tremor
Nervous system disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Urinary tract pain
Renal and urinary disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Vaccination complication
Injury, poisoning and procedural complications
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Vision blurred
Eye disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0011 affected7 at risk
EG0020 affected8 at risk
EG003
Vulvovaginal inflammation
Reproductive system and breast disorders
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Weight increased
Investigations
MedDRA 24
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Pleomorphic adenoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Injection site pain
General disorders
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Blood pressure diastolic increased
Investigations
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Blood pressure systolic increased
Investigations
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Bacterial disease carrier
Infections and infestations
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA 23.0
Systematic Assessment
EG0000 affected7 at risk
EG0010 affected7 at risk
EG0020 affected8 at risk
EG003
A safety signal had emerged in the phase 2 studies of firazorexton causing early termination of Part C and Part D of the study.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.
OG002
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG0007
OG0017
OG0028
Title
Denominators
Categories
Calcium (mmol/L): <1.92
Title
Measurements
OG0000
OG0011
OG0020
Sodium (mmol/L): <130
Title
Measurements
OG0000
OG0011
OG0020
Potassium (mmol/L): >5.3
Title
Measurements
OG0001
OG0010
OG0020
OG002
Part A: TAK-994 180 mg
TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.
Units
Counts
Participants
OG0007
OG0017
OG0028
Title
Denominators
Categories
Systolic Blood Pressure (mmHg) <90
Title
Measurements
OG0002
OG0010
OG0020
Systolic Blood Pressure (mmHg): Change from Pre-Dose >20
Title
Measurements
OG0002
OG0013
OG0022
Systolic Blood Pressure (mmHg): Change from Pre-Dose >30
Title
Measurements
OG0001
OG0011
OG0020
Systolic Blood Pressure (mmHg): Time-matched Change from Baseline > 20
Title
Measurements
OG0004
OG0017
OG0026
Systolic Blood Pressure (mmHg): Time-matched Change from Baseline > 30
Title
Measurements
OG0000
OG0013
OG0020
Diastolic blood pressure (mmHg): Change from Pre-Dose >20
Title
Measurements
OG0001
OG0013
OG0020
Diastolic blood pressure (mmHg): Time-matched Change from Baseline > 20
Title
Measurements
OG0001
OG0014
OG0023
Temperature (C): >38.5
Title
Measurements
OG0000
OG0011
OG0020
Units
Counts
Participants
OG0007
OG0017
OG0028
Title
Denominators
Categories
PR Interval (msec): ≥200
Title
Measurements
OG0000
OG0011
OG0022
QTcF Interval (msec): ≥30 change from baseline and >450
Title
Measurements
OG0001
OG0010
OG0020
QRS Duration (msec): ≤80
Title
Measurements
OG0004
OG0010
OG0025
Part B: TAK-994 90 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
OG003
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
OG004
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
Units
Counts
Participants
OG00012
OG0019
OG00211
OG0039
OG0040
Title
Denominators
Categories
Title
Measurements
OG000-2.5± 2.19
OG00123.9± 2.27
OG00227.4± 2.17
OG00332.6± 2.25
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
MMRM
The unstructured covariance structure was used for the repeated statement.
<0.001
The analysis used a linear MMRM with fixed effects for baseline (Day -1 mean values), treatment, visit, and treatment-by-visit interaction. Visit was repeated factor in the model.
LS Mean Difference
26.4
Standard Error of the Mean
3.15
2-Sided
95
20.07
32.73
Superiority
OG000
OG002
MMRM
The unstructured covariance structure was used for the repeated statement.
<0.001
The analysis used a linear MMRM with fixed effects for baseline (Day -1 mean values), treatment, visit, and treatment-by-visit interaction. Visit was repeated factor in the model.
LS Mean Difference
29.9
Standard Error of the Mean
3.08
2-Sided
95
23.68
36.07
Superiority
OG000
OG003
MMRM
The unstructured covariance structure was used for the repeated statement.
<0.001
The analysis used a linear MMRM with fixed effects for baseline (Day -1 mean values), treatment, visit, and treatment-by-visit interaction. Visit was repeated factor in the model.
LS Mean Difference
35.0
Standard Error of the Mean
3.14
2-Sided
95
28.73
41.34
Superiority
6
OG0018
Title
Denominators
Categories
Cmax (ng/mL); Following First (AM) Dose at Day 1
Title
Measurements
OG000305.5± 68.3
OG001679.1± 24.5
Cmax (ng/mL); Following Second (PM) Dose at Day 1
Title
Measurements
OG000437.1± 46.9
OG0011127± 26.4
6
OG0018
Title
Denominators
Categories
Tmax (h): Following First (AM) Dose at Day 1
Title
Measurements
OG0001.19(1.00 to 5.03)
OG0011.00(1.00 to 5.00)
Tmax (h): Following Second (PM) Dose at Day 1
Title
Measurements
OG0002.04(1.02 to 4.00)
OG0011.75(1.42 to 2.08)
6
OG0018
Title
Denominators
Categories
Title
Measurements
OG0003700± 63.0
OG0018559± 26.7
7
OG0018
Title
Denominators
Categories
Cmax (ng/mL); Following First (AM) Dose at Day 28
Title
Measurements
OG000377.5± 36.6
OG001856.9± 31.6
Cmax (ng/mL); Following Second (PM) Dose at Day 28
Title
Measurements
OG000416.0± 40.9
OG001829.4± 28.4
7
OG0018
Title
Denominators
Categories
Tmax (h): Following First (AM) Dose at Day 28
Title
Measurements
OG0001.03(0.93 to 3.10)
OG0011.00(0.90 to 1.00)
Tmax (h): Following Second (PM) Dose at Day 28
Title
Measurements
OG0002.15(2.00 to 4.05)
OG0013.46(1.50 to 7.00)
7
OG0018
Title
Denominators
Categories
Title
Measurements
OG0002968± 33.1
OG0016438± 22.6
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
OG003
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
OG004
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
Units
Counts
Participants
OG00012
OG00110
OG00211
OG0039
OG0040
Title
Denominators
Categories
Title
Measurements
OG000-2.1± 1.35
OG001-12.2± 1.41
OG002-13.5± 1.32
OG003-15.1± 1.41
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
MMRM
The unstructured covariance structure was used for the repeated statement.
<0.001
The analysis used a linear MMRM with fixed effects for baseline (Day -1 mean values), treatment, visit, and treatment-by-visit interaction. Visit was repeated factor in the model.
LS Mean Difference
-10.1
Standard Error of the Mean
1.96
2-Sided
95
-14.07
-6.16
Superiority
OG000
OG002
MMRM
The unstructured covariance structure was used for the repeated statement.
<0.001
The analysis used a linear MMRM with fixed effects for baseline (Day -1 mean values), treatment, visit, and treatment-by-visit interaction. Visit was repeated factor in the model.
LS Mean Difference
-11.4
Standard Error of the Mean
1.89
2-Sided
95
-15.20
-7.56
Superiority
OG000
OG003
MMRM
The unstructured covariance structure was used for the repeated statement.
<0.001
The analysis used a linear MMRM with fixed effects for baseline (Day -1 mean values), treatment, visit, and treatment-by-visit interaction. Visit was repeated factor in the model.
LS Mean Difference
-13.0
Standard Error of the Mean
1.95
2-Sided
95
-16.96
-9.09
Superiority
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
OG003
Part B: TAK-994 180 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
OG004
Part C: TAK-994 180 mg
TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.
Units
Counts
Participants
OG00010
OG00110
OG00211
OG0038
OG0040
Title
Denominators
Categories
Title
Measurements
OG000-6.58± 7.433
OG001-16.17± 20.979
OG002-11.91± 10.174
OG003-15.74± 9.978
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
MMRM
The Poisson regression with natural log link was on the count of cataplexy per week.
=0.002
The incidence rate was the exponentiated LS means and the incidence rate ratio (IRR) was the exponentiated LS mean differences from the generalized estimating equation (GEE) Poisson regression model.
IRR
0.05
2-Sided
95
0.007
0.317
Superiority
OG000
OG002
MMRM
The Poisson regression with natural log link was on the count of cataplexy per week.
=0.019
The incidence rate was the exponentiated LS means and the IRR was the exponentiated LS mean differences from the GEE Poisson regression model.
IRR
0.20
2-Sided
95
0.050
0.767
Superiority
OG000
OG003
MMRM
The Poisson regression with natural log link was on the count of cataplexy per week.
=0.001
The incidence rate was the exponentiated LS means and the IRR was the exponentiated LS mean differences from the GEE Poisson regression model.
IRR
0.15
2-Sided
95
0.047
0.482
Superiority
OG003
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
OG004
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
Units
Counts
Participants
OG00017
OG00117
OG00220
OG00319
OG0042
Title
Denominators
Categories
Title
Measurements
OG0004
OG00113
OG00217
OG00314
OG0042
OG003
Part B: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
OG004
Part C: TAK-994 180 mg
TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.
Units
Counts
Participants
OG00017
OG00117
OG00220
OG00319
OG0042
Title
Denominators
Categories
Alanine Aminotransferase (ALT) [U/L)]: >3 × Upper limit normal (ULN)