A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy
Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2)
About this trial
This is an interventional treatment trial for Narcolepsy Type 1 (NT1) focused on measuring Drug therapy
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.
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
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
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
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.