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A Study of TAK-994 in Participants With Narcolepsy Type 1

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ClinicalTrials.gov Identifier: NCT04096560
Recruitment Status : Not yet recruiting
First Posted : September 20, 2019
Last Update Posted : September 20, 2019
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 type 1 (NT1).

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

Detailed Description:

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

The study will enrol up to approximately 72 patients. Participants will be randomly assigned (by chance, like flipping a coin) in 2:1 ratio to one of the two treatment groups as 3 Cohorts:

Cohort 1: TAK-994 tablets dose Level 1 or placebo Cohort 2: TAK-994 tablets TBD or placebo Cohort 3: TAK-994 tablets TBD or placebo

This multi-center trial will be conducted in the North America and Japan. 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 : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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 Type 1
Estimated Study Start Date : January 2, 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
TAK-994 tablets, dose level 1 for 28 days or TAK-994 placebo-matching tablets for 28 days.
Drug: TAK-994
TAK-994 tablets

Drug: Placebo
TAK-994 placebo-matching tablets

Experimental: Cohort 2
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.
Drug: TAK-994
TAK-994 tablets

Drug: Placebo
TAK-994 placebo-matching tablets

Experimental: Cohort 3
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.
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 timepoints (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 timepoints (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 timepoints (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 timepoints (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 timepoints (Up to 14 hours) post-dose ]
  6. Day 28, AUC(0-t): Area Under the Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration After Multiple Doses of TAK-994 [ Time Frame: Day 28: Pre-dose and at multiple timepoints (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: Baseline and Days 1, 14, and 28 ]
    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 28 ]
    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. 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

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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. Must have a diagnosis of narcolepsy type 1 (NT1), as defined by the international classification of sleep disorders, 3rd edition (ICSD-3) criteria.
  2. The participant's Epworth Sleepiness Scale (ESS) score must be ≥10 at screening.
  3. Must be willing to discontinue all medications used for the treatment of NT1 during the screening period.
  4. Must have human leukocyte antigen (HLA) narcolepsy test positivity (HLA DQB1*06:02).
  5. Must have ≥4 episodes of cataplexy/week reported during the screening period before washout of anticataplexy medications.

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 6 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 cancer); a current or prior history of substance abuse disorder; past or current epilepsy, seizure, tremor, or disorders of related symptoms; 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 or anticonvulsant agents 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 (eg, anxiety, depression, epilepsy, heart disease, or significant hepatic, pulmonary, or renal disease) that requires the subject to take excluded medications.

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

Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Takeda

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT04096560     History of Changes
Other Study ID Numbers: TAK-994-1501
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019
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
Disorders of Excessive Somnolence
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders