Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of TAK-988 in Healthy Participants

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: NCT04082481
Recruitment Status : Not yet recruiting
First Posted : September 9, 2019
Last Update Posted : May 11, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE September 5, 2019
First Posted Date  ICMJE September 9, 2019
Last Update Posted Date May 11, 2020
Estimated Study Start Date  ICMJE November 13, 2020
Estimated Primary Completion Date January 11, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
  • Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 26 ]
  • Number of Participants With at Least one Markedly Abnormal Value (MAV) for Laboratory Values [ Time Frame: Baseline up to Day 26 ]
  • Number of Participants With at Least one MAV for Vital Signs [ Time Frame: Baseline up to Day 26 ]
  • Number of Participants With at Least one MAV for Electrocardiograms (ECGs) [ Time Frame: Baseline up to Day 26 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2019)
  • Cmax: Maximum Observed Plasma Concentration for TAK-988 [ Time Frame: Day 1 (Parts A-E), Day 7 (Part C), Day 14 (Parts B and D), Day 17 (Part E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-988 [ Time Frame: Day 1 (Parts A-E), Day 7 (Part C), Day 14 (Parts B and D), Day 17 (Part E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-988 [ Time Frame: Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-988 [ Time Frame: Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • T1/2z: Terminal Disposition Phase Half-life for TAK-988 [ Time Frame: Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • CLR: Renal Clearance for TAK-988 [ Time Frame: Day 1 (Parts A, B, D and E), Day 14 (Parts B and D), Day 17 (Part E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to tau over Dosing Interval for TAK-988 [ Time Frame: Day 7 (Part C), Day 14 (Parts B and D), Day 17 (Part E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • Part C: Ratio of the Cerebrospinal Fluid (CSF) to Plasma AUC From Time 0 to 24 Hours for TAK-988 [ Time Frame: Day 7 (Part C) Pre-dose and at multiple time points (up to 24 hours) post-dose ]
  • Rac (AUC): Accumulation Ratio Based on AUCτ for TAK-988 [ Time Frame: Day 7 (Part C), Day 14 (Parts B and D), Day 17 (Part E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of TAK-988 in Healthy Participants
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Rising Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-988 in Healthy Subjects
Brief Summary The purpose of this study is to assess the safety and tolerability of TAK-988 following single and multiple oral doses in healthy non-Japanese and Japanese adult participants and healthy elderly (HE) participants.
Detailed Description

The drug being tested in this study is called TAK-988. TAK-988 is being tested to evaluate safety, tolerability, PK, and PD of single and multiple oral doses in healthy non-Japanese and Japanese adult participants and HE participants.

The study will enroll approximately 156 healthy participants. The study consists of 5 parts and up to 19 cohorts as mentioned below:

  • TAK-988, Part A: Single-rising dose (SRD) design to assess the safety, tolerability, and PK of TAK-988 and effect of food on the PK of the TAK-988
  • TAK-988, Part B: MRD design to assess the safety, tolerability, PK and PD of TAK-988
  • TAK-988, Part C: MRD design to assess the safety, tolerability, PK and PD of TAK-988 and also central nervous system penetration relative to plasma concentrations of TAK-988
  • TAK-988, Part D: MRD design to assess the safety, tolerability, PK and PD of TAK-988 for HE participants
  • TAK-988, Part E: SRD and MRD design to assess the safety, tolerability, PK and PD of TAK-988 for Japanese origin participants

Participants in each cohort will be randomized to receive treatment with TAK-988 or matching placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

This multi-center trial will be conducted in the United States. The overall duration of the study is approximately 10.5 months. Participants will make a final visit 7 days after receiving their last dose of study drug for a follow-up assessment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Condition  ICMJE Healthy Volunteers
Intervention  ICMJE
  • Drug: TAK-988
    TAK-988 tablets.
  • Drug: TAK-988 Placebo
    TAK-988 placebo-matching tablets.
Study Arms  ICMJE
  • Experimental: TAK-988: Part A
    TAK-988 tablet or TAK-988 placebo-matching tablet, orally, once on Day 1 to healthy non-Japanese participants. Sentinel dosing will be done in the first 2 cohorts of Part A (Cohorts A1 and A2 [fasted and fed dosing conditions]). Dose escalation in Cohorts A2 to A6 will be based on emerging safety/tolerability, PK, and PD data from previous cohorts.
    Interventions:
    • Drug: TAK-988
    • Drug: TAK-988 Placebo
  • Experimental: TAK-988: Part B
    TAK-988 tablet or TAK-988 placebo-matching tablet, orally, twice daily (6-hour interval) from Day 1 to Day 14 to healthy non-Japanese participants. Dose escalation will be based on review of the emerging safety/tolerability, PK, and PD data from previous cohorts and Part A.
    Interventions:
    • Drug: TAK-988
    • Drug: TAK-988 Placebo
  • Experimental: TAK-988: Part C
    TAK-988 tablet or TAK-988 placebo-matching tablet, orally, twice daily (6-hour interval) from Day 1 to Day 7 to healthy non-Japanese participants. Dose will be determined based on previous multiple-rising dose (MRD) cohorts.
    Interventions:
    • Drug: TAK-988
    • Drug: TAK-988 Placebo
  • Experimental: TAK-988: Part D
    TAK-988 tablet or TAK-988 placebo-matching tablet, orally, twice daily (6-hour interval) from Day 1 to Day 14 to HE non-Japanese participants. Dose will be determined based on previous MRD cohorts.
    Interventions:
    • Drug: TAK-988
    • Drug: TAK-988 Placebo
  • Experimental: TAK-988: Part E
    TAK-988 tablet or TAK-988 placebo-matching tablet, orally, once on Day 1, followed by a washout period of 2 days and twice daily (6- hour interval) on Day 3 and continue to Day 17 to healthy Japanese participants. Dose will be determined based on previous MRD cohorts.
    Interventions:
    • Drug: TAK-988
    • Drug: TAK-988 Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 5, 2019)
156
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 11, 2021
Estimated Primary Completion Date January 11, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Be normotensive, with no history of hypertension or use of antihypertensive medication. Blood pressure (BP) must be less than (<) 140 millimeter of mercury (mmHg) (systolic) and <90 mmHg (diastolic).

    Healthy Adult and Elderly Participants (Parts A through D)

  2. Must have a body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 30.0 kilogram per square meter (kg/m^2) at the screening visit (non-Japanese only).

    Healthy Adult Participants (Parts A, B, and C)

  3. Must be aged 18 to 55 years, inclusive, at the screening visit.
  4. Must have a body weight >=50 kilogram (kg) at the screening visit.

    HE Participants (Part D)

  5. Must be aged >=65 years, inclusive, at the time of informed consent.
  6. Must have a body weight >=40 kg at the screening visit.

    Healthy Japanese Adult Participants (Part E)

  7. Must be aged 18 to 55 years, inclusive, at the screening visit.
  8. Must have a BMI >=18.0 and <=26.0 kg/m^2 at the screening visit.
  9. Must have been born in Japan to a Japanese mother and father and have maternal and paternal Japanese grandparents.
  10. Must have not been away from Japan for more than 10 years at the screening visit.
  11. In the opinion of the investigator, must have a lifestyle that has not changed significantly since relocation from Japan.

Exclusion Criteria:

  1. Has a known hypersensitivity to any component of the formulation of TAK-988 or related compounds.
  2. 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.
  3. Has a lifetime history of major psychiatric disorder, such as bipolar disorder or schizophrenia. Participant who have history of major depressive disorder (MDD) may be included, but participants who have current active MDD or who have had active MDD in the past 6 months are excluded.
  4. Has a clinically significant history of head injury or head trauma.
  5. Has a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
  6. Screening electrocardiogram (ECG) reveals a QT interval with the Fridericia's correction method (QTcF) greater than (>) 450 millisecond (ms) (men) or >470 ms (women).
  7. Has a resting heart rate outside of the range of 45 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes).

    Healthy Non-Japanese Adult Participants (Part C)

  8. Has undergone CSF collection within 30 days before check-in (Day -2).
  9. Has a known hypersensitivity to anesthesia or its derivatives used during CSF collection or to any medication used to prepare the area of lumbar puncture.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04082481
Other Study ID Numbers  ICMJE TAK-988-1001
U1111-1238-5474 ( Registry Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Takeda
PRS Account Takeda
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP