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

NCT ID: NCT04096560

Last Updated: 2024-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-27
• Study Completion Date: 2021-11-05

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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A: Placebo

TAK-994 placebo-matching tablets, orally, twice daily (BID) for 28 days, in participants with NT1.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TAK-994 placebo-matching tablets.

Part A: TAK-994 120 mg

TAK-994 120 mg, orally, BID for 28 days, in participants with NT1.

Group Type: EXPERIMENTAL

TAK-994

Intervention Type: DRUG

TAK-994 tablets.

Part A: TAK-994 180 mg

TAK-994 180 mg, orally, BID for 28 days, in participants with NT1.

Group Type: EXPERIMENTAL

TAK-994

Intervention Type: DRUG

TAK-994 tablets.

Part B: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TAK-994 placebo-matching tablets.

Part B: TAK-994 30 mg

TAK-994 30 mg tablets, orally, BID for 56 days, in participants with NT1.

Group Type: EXPERIMENTAL

TAK-994

Intervention Type: DRUG

TAK-994 tablets.

Part B: TAK-994 90 mg

TAK-994 90 mg tablets, orally, BID for 56 days, in participants with NT1.

Group Type: EXPERIMENTAL

TAK-994

Intervention Type: DRUG

TAK-994 tablets.

Part B: TAK-994 180 mg

TAK-994 180 mg tablets, orally, BID for 56 days, in participants with NT1.

Group Type: EXPERIMENTAL

TAK-994

Intervention Type: DRUG

TAK-994 tablets.

Part C: TAK-994 180 mg

TAK-994 180 mg tablets, orally, BID for 56 days, in Chinese participants with NT1.

Group Type: EXPERIMENTAL

TAK-994

Intervention Type: DRUG

TAK-994 tablets.

Interventions

TAK-994

TAK-994 tablets.

Intervention Type: DRUG

Placebo

TAK-994 placebo-matching tablets.

Intervention Type: DRUG

Other Intervention Names

Firazorexton

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Wright Clinical Research

Alabaster, Alabama, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

CITrials - Bellflower

Bellflower, California, United States

Santa Monica Clinical Trials

Los Angeles, California, United States

Stanford School of Medicine

Redwood City, California, United States

Pacific Research Network, Inc

San Diego, California, United States

SDS Clinical Trials, Inc.

Santa Ana, California, United States

Alpine Clinical Research Center

Boulder, Colorado, United States

Delta Waves Sleep Disorders and Research Center

Colorado Springs, Colorado, United States

St. Francis Medical Institute

Clearwater, Florida, United States

Sleep Medicine Specialists of South Florida

Miami, Florida, United States

Clinical Trials of Florida

Miami, Florida, United States

JSV Clinical Research Study, Inc

Tampa, Florida, United States

Florida Pulmonary Research Institute, LLC

Winter Park, Florida, United States

NeuroTrials Research, Inc.

Atlanta, Georgia, United States

iResearch Atlanta, LLC

Decatur, Georgia, United States

Sleep Practitioners, LLC

Macon, Georgia, United States

Global Research Associates

Stockbridge, Georgia, United States

Hawaii Pacific Neuroscience

Honolulu, Hawaii, United States

Lutheran Sleep Disorder Center

Fort Wayne, Indiana, United States

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Helene A. Emsellem, MD PC trading as "The Center for Sleep & Wake Disorders"

Chevy Chase, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Neurocare, Inc., dba Neurocare Center for Research

Newton, Massachusetts, United States

Research Carolina Elite LLC

Denver, North Carolina, United States

Clinical Research of Gastonia

Gastonia, North Carolina, United States

Raleigh Neurology Associates

Raleigh, North Carolina, United States

CTI Clinical Research Center

Cincinnati, Ohio, United States

Intrepid Research

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio Sleep Medicine and Neuroscience Institute

Dublin, Ohio, United States

Respiratory Specialists

Wyomissing, Pennsylvania, United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Bogan Sleep Consultants, LLC

Columbia, South Carolina, United States

Sleep Therapy & Research Center

San Antonio, Texas, United States

Comprehensive Sleep Medicine Associates

Sugar Land, Texas, United States

West Ottawa Sleep Centre

Ottawa, Ontario, Canada

Toronto Sleep Institute

Toronto, Ontario, Canada

Jodha Tishon Inc.

Toronto, Ontario, Canada

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Jinan University

Tianhe, Guangdong, China

The First Hospital of Jilin University

Changchun, Jilin, China

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Terveystalo Helsinki Uniklinikka

Helsinki, , Finland

Turku University Hospital

Turku, , Finland

Hopital Gui de Chauliac

Montpellier, Herault, France

Hopital Roger Salengro - CHU Lille

Lille, Nord, France

SomnoCenter Budapest

Budapest, , Hungary

IRCCS Oasi Maria SS

Troina, Enna, Italy

Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche

Bologna, , Italy

Ospedale San Raffaele (San Raffaele Turro)

Milan, , Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, , Italy

SOUSEIKAI PS Clinic

Fukuoka, Fukuoka, Japan

You Ariyoshi Sleep Clinic

Kitakyushu-shi, Fukuoka, Japan

Kurume University Hospital

Kurume-shi, Fukuoka, Japan

Kaiseikai Kita Shin Yokohama Internal Medicine Clinic

Yokohama, Kanagawa, Japan

Howakai Kuwamizu Hospital

Kumamoto, Kumamoto, Japan

Jinyukai Kotorii Isahaya Hospital

Isahaya-shi, Nagasaki, Japan

Shunkaikai Inoue Hospital

Nagasaki, Nagasaki, Japan

Gokeikai Osaka Kaisei Hospital

Osaka, Osaka, Japan

Kyowakai Hannan Hospital

Sakai-shi, Osaka, Japan

Koishikawa Tokyo Hospital

Bunkyō City, Tokyo-To, Japan

Nihon University Itabashi Hospital

Itabashi-ku, Tokyo-To, Japan

Yoyogi Sleep Disorder Center

Shibuya-ku, Tokyo-To, Japan

Sleep Support Clinic

Shinagawa-ku, Tokyo-To, Japan

Sleep & Stress Clinic

Shinagawa-ku, Tokyo-To, Japan

Sumida Hospital

Sumida-ku, Tokyo-To, Japan

Stichting Epilepsie Instelling Nederland, Heemstede

Heemstede, , Netherlands

Kempenhaeghe, Heeze

Heeze, , Netherlands

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, South Korea

Keimyung University Dongsan Hospital

Daegu, , South Korea

Hospital Universitario Araba Sede Santiago

Vitoria-Gasteiz, Alava, Spain

Hospital General de Castellon

Castellon, Castellon, Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Vithas Nuestra Senora de America

Madrid, , Spain

Countries

United States; Canada; China; Czechia; Finland; France; Hungary; Italy; Japan; Netherlands; South Korea; Spain

References

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.

Reference Type: DERIVED

PMID: 37494485 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b603c4db2bf003ab4a34e

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

Other Identifiers

JapicCTI-205178

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-000777-24

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1240-0346

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-994-1501

Identifier Type: -

Identifier Source: org_study_id