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

NCT04096560 | Terminated Phase 2 Results FDA Drug

• 4 other identifiers: TAK-994-1501JapicCTI-2051782020-000777-24U1111-1240-0346
• Study Type: interventional
• Target: 97
• Locations: 12 countries
• Sites: 78

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.

Conditions

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

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (5)

• 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.

  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

Secondary Outcomes (12)

• 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

  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

Study Arms (8)

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.

Drug: TAK-994

Part B: TAK-994 180 mg

EXPERIMENTAL

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

Interventions

TAK-994 DRUG

TAK-994 tablets.

Also known as: Firazorexton

Part A: TAK-994 120 mg; Part A: TAK-994 180 mg; Part B: TAK-994 180 mg; Part B: TAK-994 30 mg; Part B: TAK-994 90 mg; Part C: TAK-994 180 mg

Placebo DRUG

TAK-994 placebo-matching tablets.

Part A: Placebo; Part B: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (78)

Wright Clinical Research

Alabaster, Alabama, 35007, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

CITrials - Bellflower

Bellflower, California, 90706, United States

Location

Santa Monica Clinical Trials

Los Angeles, California, 90025, United States

Location

Stanford School of Medicine

Redwood City, California, 94063, United States

Location

Pacific Research Network, Inc

San Diego, California, 92128, United States

Location

SDS Clinical Trials, Inc.

Santa Ana, California, 92705, United States

Location

Alpine Clinical Research Center

Boulder, Colorado, 80301, United States

Location

Delta Waves Sleep Disorders and Research Center

Colorado Springs, Colorado, 80918, United States

Location

St. Francis Medical Institute

Clearwater, Florida, 33765, United States

Location

Sleep Medicine Specialists of South Florida

Miami, Florida, 33126, United States

Location

Clinical Trials of Florida

Miami, Florida, 33186, United States

Location

JSV Clinical Research Study, Inc

Tampa, Florida, 33624, United States

Location

Florida Pulmonary Research Institute, LLC

Winter Park, Florida, 32789, United States

Location

NeuroTrials Research, Inc.

Atlanta, Georgia, 30328, United States

Location

iResearch Atlanta, LLC

Decatur, Georgia, 30030, United States

Location

Sleep Practitioners, LLC

Macon, Georgia, 31210, United States

Location

Global Research Associates

Stockbridge, Georgia, 30281, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Lutheran Sleep Disorder Center

Fort Wayne, Indiana, 46804, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

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

Chevy Chase, Maryland, 20815, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Neurocare, Inc., dba Neurocare Center for Research

Newton, Massachusetts, 02459, United States

Location

Research Carolina Elite LLC

Denver, North Carolina, 28037, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

CTI Clinical Research Center

Cincinnati, Ohio, 45245, United States

Location

Intrepid Research

Cincinnati, Ohio, 45245, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio Sleep Medicine and Neuroscience Institute

Dublin, Ohio, 43017, United States

Location

Respiratory Specialists

Wyomissing, Pennsylvania, 19610, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Bogan Sleep Consultants, LLC

Columbia, South Carolina, 29201, United States

Location

Sleep Therapy & Research Center

San Antonio, Texas, 78229, United States

Location

Comprehensive Sleep Medicine Associates

Sugar Land, Texas, 77478, United States

Location

West Ottawa Sleep Centre

Ottawa, Ontario, K2A3Z8, Canada

Location

Toronto Sleep Institute

Toronto, Ontario, M4P 1P2, Canada

Location

Jodha Tishon Inc.

Toronto, Ontario, M5S 3A3, Canada

Location

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, 100053, China

Location

The First Affiliated Hospital of Jinan University

Tianhe, Guangdong, 510630, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50333, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

Terveystalo Helsinki Uniklinikka

Helsinki, 380, Finland

Location

Turku University Hospital

Turku, 20521, Finland

Location

Hopital Gui de Chauliac

Montpellier, Herault, 34295, France

Location

Hopital Roger Salengro - CHU Lille

Lille, Nord, 59037, France

Location

SomnoCenter Budapest

Budapest, 1012, Hungary

Location

IRCCS Oasi Maria SS

Troina, Enna, 94018, Italy

Location

Universita di Bologna-Clinica Neurologica-Dipartimento di Scienze Neurologiche

Bologna, 40123, Italy

Location

Ospedale San Raffaele (San Raffaele Turro)

Milan, 20127, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, 133, Italy

Location

SOUSEIKAI PS Clinic

Fukuoka, Fukuoka, 812-0025, Japan

Location

You Ariyoshi Sleep Clinic

Kitakyushu-shi, Fukuoka, 802-0084, Japan

Location

Kurume University Hospital

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Kaiseikai Kita Shin Yokohama Internal Medicine Clinic

Yokohama, Kanagawa, 223-0059, Japan

Location

Howakai Kuwamizu Hospital

Kumamoto, Kumamoto, 862-0954, Japan

Location

Jinyukai Kotorii Isahaya Hospital

Isahaya-shi, Nagasaki, 854-0081, Japan

Location

Shunkaikai Inoue Hospital

Nagasaki, Nagasaki, 850-0045, Japan

Location

Gokeikai Osaka Kaisei Hospital

Osaka, Osaka, 532-0003, Japan

Location

Kyowakai Hannan Hospital

Sakai-shi, Osaka, 599-8263, Japan

Location

Koishikawa Tokyo Hospital

Bunkyō City, Tokyo-To, 112-0012, Japan

Location

Nihon University Itabashi Hospital

Itabashi-ku, Tokyo-To, 173-8610, Japan

Location

Yoyogi Sleep Disorder Center

Shibuya-ku, Tokyo-To, 151-0053, Japan

Location

Sleep Support Clinic

Shinagawa-ku, Tokyo-To, 140-0011, Japan

Location

Sleep & Stress Clinic

Shinagawa-ku, Tokyo-To, 141-6003, Japan

Location

Sumida Hospital

Sumida-ku, Tokyo-To, 130-0004, Japan

Location

Stichting Epilepsie Instelling Nederland, Heemstede

Heemstede, 2103 SW, Netherlands

Location

Kempenhaeghe, Heeze

Heeze, 5591 VE, Netherlands

Location

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

Suwon, Gyeonggi-do, 16247, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

Location

Hospital Universitario Araba Sede Santiago

Vitoria-Gasteiz, Alava, 1004, Spain

Location

Hospital General de Castellon

Castellon, Castellon, 12004, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Vithas Nuestra Senora de America

Madrid, 28043, Spain

Location

Related Publications (1)

• 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.

  PMID: 37494485 DERIVED

Related Links

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

Limitations and Caveats

A safety signal had emerged in the phase 2 studies of firazorexton causing early termination of Part C and Part D of the study.

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 20, 2019
• Study Start: May 27, 2020
• Primary Completion: November 5, 2021
• Study Completion: November 5, 2021
• Last Updated: October 29, 2024
• Results First Posted: October 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.

Locations

CA (3); HU (1); FI (2); CZ (3); JP (15); CN (4); NL (2); KR (2); FR (2); US (36); IT (4); ES (4)