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A Study of TAK-994 in Participants With Narcolepsy With or Without Cataplexy (Narcolepsy Type 1 [NT1] or Narcolepsy Type 2 [NT2])

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04096560
Recruitment Status : Recruiting
First Posted : September 20, 2019
Last Update Posted : June 26, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to assess the safety and tolerability of TAK-994 following multiple oral doses in participants with narcolepsy with or without cataplexy (NT1 or NT2).

Condition or disease Intervention/treatment Phase
Narcolepsy Type 1 Narcolepsy Type 2 Drug: TAK-994 Drug: Placebo Phase 2

Detailed Description:

The drug being tested in this study is called TAK-994.

The study will enroll up to approximately 126 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 2:1 ratio to one of the 6 treatment Cohorts:

Cohort 1, NT1 Participants: TAK-994 Dose Level 1 Cohort 2, NT1 Participants: TAK-994 TBD Cohort 3, NT1 Participants: TAK-994 TBD Cohort 4, NT1 Participants in China: TAK-994 Cohort 5, NT2 Participants: TAK-994 Cohort 6, NT2 Participants: TAK-994

This multi-center trial will be conducted in the North America, Japan, China, and European Union. The overall duration of the study is 35 days. Participants will be followed up for 7 days after the last dose of study drug.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 27, 2020
Estimated Primary Completion Date : May 28, 2021
Estimated Study Completion Date : May 28, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1, NT1 Participants: TAK-994 Dose Level 1
TAK-994 tablets, dose level 1 for 28 days or TAK-994 placebo-matching tablets for 28 days, in participants with NT1.
Drug: TAK-994
TAK-994 tablets.

Drug: Placebo
TAK-994 placebo-matching tablets.

Experimental: Cohort 2, NT1 Participants: TAK-994 TBD
TAK-994 tablets, dose to be determined (TBD) based on safety and tolerability in Cohort 1, for 28 days or TAK-994 placebo-matching tablets for 28 days, in participants with NT1.
Drug: TAK-994
TAK-994 tablets.

Drug: Placebo
TAK-994 placebo-matching tablets.

Experimental: Cohort 3, NT1 Participants: TAK-994 TBD
TAK-994 tablets, dose TBD based on safety and tolerability in Cohort 2, for 28 days or TAK-994 placebo-matching tablets for 28 days, in participants with NT1.
Drug: TAK-994
TAK-994 tablets.

Drug: Placebo
TAK-994 placebo-matching tablets.

Experimental: Cohort 4, NT1 Participants in China: TAK-994
TAK-994 tablets, dose TBD based on safety and tolerability in Cohort 3, for 28 days or TAK-994 placebo-matching tablets for 28 days, in participants with NT1 in China.
Drug: TAK-994
TAK-994 tablets.

Drug: Placebo
TAK-994 placebo-matching tablets.

Experimental: Cohort 5, NT2 Participants: TAK-994
TAK-994 tablets, dose TBD based on safety and tolerability in Cohort 4, for 28 days or TAK-994 placebo-matching tablets for 28 days, in participants with NT2.
Drug: TAK-994
TAK-994 tablets.

Drug: Placebo
TAK-994 placebo-matching tablets.

Experimental: Cohort 6, NT2 Participants: TAK-994
TAK-994 tablets, dose TBD based on safety and tolerability in Cohort 5, for 28 days or TAK-994 placebo-matching tablets for 28 days, in participants with NT2.
Drug: TAK-994
TAK-994 tablets.

Drug: Placebo
TAK-994 placebo-matching tablets.




Primary Outcome Measures :
  1. Number of Participants who Experience at least 1 Treatment Emergent Adverse Events (TEAEs) During the Study [ Time Frame: Baseline up to Day 35 ]
    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.

  2. Number of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at least Once Postdose During the Study [ Time Frame: Baseline up to Day 35 ]
    Standard safety laboratory values (serum chemistry, hematology, and urine analysis) will be collected and compared to pre-specified criteria for markedly abnormal values throughout the study.

  3. Number of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at least Once Postdose During the Study [ Time Frame: Baseline up to Day 35 ]
    Vital signs (body temperature, heart rate, respiratory rate, sitting blood pressure and pulse) will be collected and compared to pre-specified criteria for markedly abnormal values throughout the study.

  4. Number of Participants who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at least Once Postdose During the Study [ Time Frame: Baseline up to Day 35 ]
    A 12 lead ECG will be performed, the ECG values will be compared to pre-specified criteria for markedly abnormal values.


Secondary Outcome Measures :
  1. Day 1, Cmax: Maximum Observed Plasma Concentration After Single Dose of TAK-994 [ Time Frame: Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose ]
  2. Day 1, Tmax: Time of First Occurrence of Cmax After Single Dose of TAK-994 [ Time Frame: Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose ]
  3. Day 1, AUC(0-last): Area Under the Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration After Single Dose of TAK-994 [ Time Frame: Day 1: Pre-dose and at multiple time points (Up to 14 hours) post-dose ]
  4. Day 28, Cmax: Maximum Observed Plasma Concentration After Multiple Doses of TAK-994 [ Time Frame: Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose ]
  5. Day 28, Tmax: Time of First Occurrence of Cmax After Multiple Doses of TAK-994 [ Time Frame: Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose ]
  6. Day 28, AUC(0-t): Area Under the Concentration-time Curve from Time 0 to Time tau Over a Dosing Interval of TAK-994 [ Time Frame: Day 28: Pre-dose and at multiple time points (Up to 14 hours) post-dose ]

Other Outcome Measures:
  1. Change from Baseline in Sleep Latency as Assessed by the Maintenance of Wakefulness Test (MWT) [ Time Frame: Cohorts 1 to 4: Baseline and Days 1, 14, and 28; Cohorts 5 and 6: Baseline and Days 1, 14, 21 ]
    The MWT is a validated, objective measure that evaluates a person's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants will be instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session will be recorded on electroencephalography (EEG). If no sleep has been observed according to these rules, then the latency will be defined as 40 minutes.

  2. Change From Baseline in Subjective Daytime Sleepiness as Assessed by Epworth Sleepiness Scale (ESS) Score [ Time Frame: Baseline and Days 7, 14, 21, and 29 ]
    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.

  3. Cohorts 1 to 4: Change From Baseline in Weekly Cataplexy Rate (WCR) as Reported in the Patient-Reported Sleep Diary [ Time Frame: Baseline and Days 7, 14, 21 and 28 ]
    Participants will complete a daily patient-reported sleep diary to record self-reported narcolepsy symptoms. Participants will record episodes of cataplexy in the diary. The total number of events per week will be calculated.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has a diagnosis of narcolepsy type 1 (NT1) (Cohorts 1-4) or NT2 (Cohorts 5-6) 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. Must have human leukocyte antigen (HLA) genotype test positive for HLA DQB1*06:02 (Cohorts 1-4).
  5. Must have >=4 partial or complete episodes of cataplexy/weekby history when off of anticataplexy medications and >=4 partial or complete episodes of cataplexy/week during the screening period when off of anticataplexy medications, averaged over 2 weeks minimum, with a >=80 percent (%) compliance rate in completion of the self-reported electronic diary for cataplexy episodes (Cohorts 1-4).

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 prior 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.
  4. Used any product with stimulating or sedating properties within 7 days or 5 times the elimination half-lives (whichever is greater) prior to dosing.
  5. Has a medical disorder (including moderate to severe sleep apnea syndrome), other than narcolepsy, associated with excessive daytime sleepiness or has any other medical condition (e.g, anxiety, depression, epilepsy, heart disease, or significant hepatic, pulmonary, or renal disease) that requires the participant to take excluded medications.
  6. 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 with significant jet lag within 14 days before Study Day -2.
  7. 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 (Cohorts 1-3 and 5-6 only).

  8. Has a local infection at the puncture site.
  9. Has developed signs of lumbar radiculopathy, including lower extremity pain and paresthesia.
  10. Has any known focal neurological deficit that might suggest an increase in intracranial pressure.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04096560


Contacts
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Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

Locations
Show Show 43 study locations
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director, Clinical Science Takeda
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04096560    
Other Study ID Numbers: TAK-994-1501
JapicCTI-205178 ( Registry Identifier: JapicCTI )
2020-000777-24 ( Registry Identifier: EudraCT )
U1111-1240-0346 ( Registry Identifier: WHO )
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: June 26, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Drug therapy
Additional relevant MeSH terms:
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Narcolepsy
Cataplexy
Disorders of Excessive Somnolence
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders