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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/14/2021.

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-994 in Healthy Participants

Clinicaltrials.gov identifier NCT03933488

Recruitment Status Completed

First Posted May 1, 2019

Last update posted June 24, 2020

Study Description

Brief summary:

The purpose of this study is to assess the safety and tolerability of TAK-994 following single and multiple oral doses in healthy non-Japanese and Japanese adult participants and healthy elderly participants.

  • Condition or Disease:Healthy Participants
  • Intervention/Treatment: Drug: TAK-994
    Drug: TAK-994 Placebo
  • Phase: Phase 1
Detailed Description

The drug being tested in this study is called TAK-994. TAK-994 is being tested to find a safe and well-tolerated dose in healthy participants (non-Japanese and Japanese) and healthy elderly participants. The study will enroll up to approximately 160 healthy participants. The study consists of 6 parts and up to 20 cohorts as mentioned below. - TAK-994: Part A: Single-rising dose (SRD) design to assess the safety, tolerability, and PK of TAK-994 and effect of food on the PK of the TAK-994 - TAK-994: Part B: MRD design to assess the safety, tolerability, PK and PD of TAK-994 - TAK-994: Part C: MRD design to assess the safety, tolerability, PK and PD of TAK-994 and also central nervous system penetration relative to plasma concentrations of TAK-994 - TAK-994: Part D: MRD design to assess the safety, tolerability, PK and PD of TAK-994 for HE participants - TAK-994: Part E: SRD and MRD design to assess the safety, tolerability, PK and PD of TAK-994 for Japanese origin participants - TAK-994: Part F (Optional Cohort): Nonrandomized design to assess orexin (OX) levels in the cerebrospinal fluid (CSF) of untreated healthy adult participants. Participants in each cohort will be randomized to receive treatment with TAK-994 or matching placebo which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). Participants in optional Part F will receive no study drug. This multi-center trial will be conducted in the United States. The overall duration of the study is approximately 10 months. Participants will be followed up for 7 days after the last dose of study drug for a follow-up assessment.

Study Design
  • Study Type: Interventional
  • Actual Enrollment: 121 participants
  • Allocation: Randomized
  • Intervention Model: Sequential Assignment
  • Masking: Double (Participant, Investigator)
  • Primary Purpose: Other
  • Official Title: A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Rising Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-994 in Healthy Subjects
  • Actual Study Start Date: May 2019
  • Actual Primary Completion Date: March 2020
  • Actual Study Completion Date: March 2020
Arms and interventions
Arm Intervention/treatment
Experimental: TAK-994: Part A
TAK-994 tablet or matching placebo, 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, and PK (pharmacokinetic) data from previous cohorts.
Drug: TAK-994
TAK-994 tablets.

Drug: TAK-994 Placebo
TAK-994 placebo-matching tablets.
Experimental: TAK-994: Part B
TAK-994 tablet or matching placebo, orally, once daily or twice daily from Day 1 to Day 14 to healthy non-Japanese participants. Dose escalation will be based on review of the emerging safety, PK, and PD (pharmacodynamic) data from Part A. Fixed-dose titration regimens may also be evaluated based on review of the emerging safety, PK, and tolerability data from previous cohorts.
Drug: TAK-994
TAK-994 tablets.

Drug: TAK-994 Placebo
TAK-994 placebo-matching tablets.
Experimental: TAK-994: Part C
TAK-994 tablet or matching placebo, orally, once daily or twice daily from Day 1 to Day 7 to healthy non-Japanese participants. Dose will be determined based on previous multiple-rising dose (MRD) cohorts.
Drug: TAK-994
TAK-994 tablets.

Drug: TAK-994 Placebo
TAK-994 placebo-matching tablets.
Experimental: TAK-994: Part D
TAK-994 tablet or matching placebo, orally, once daily or twice daily from Day 1 to Day 14 to healthy non-Japanese elderly participants. Dose will be determined based on previous MRD cohorts. Fixed-dose titration regimens may also be evaluated based on review of the emerging safety, PK, and tolerability data from previous cohorts.
Drug: TAK-994
TAK-994 tablets.

Drug: TAK-994 Placebo
TAK-994 placebo-matching tablets.
Experimental: TAK-994: Part E
TAK-994 tablet or matching placebo, orally, once or twice on Day 1, followed by a washout period of 2 days and on Day 4 and continue to Day 17 to healthy Japanese participants. Dose will be determined based on previous MRD cohorts. Fixed-dose titration regimens may also be evaluated based on review of the emerging safety, PK, and tolerability data from previous cohorts.
Drug: TAK-994
TAK-994 tablets.

Drug: TAK-994 Placebo
TAK-994 placebo-matching tablets.
Outcome Measures
  • Primary Outcome Measures: 1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) [ Time Frame: Baseline up to Day 26 ]
  • 2. Number of Participants With at Least one Markedly Abnormal Laboratory Value [ Time Frame: Baseline up to Day 26 ]
  • 3. Number of Participants With at Least one Markedly Abnormal Laboratory Value for Vital Signs [ Time Frame: Baseline up to Day 26 ]
  • 4. Number of Participants With at Least one Markedly Abnormal Laboratory Value for Electrocardiogram (ECG) [ Time Frame: Baseline up to Day 26 ]
  • Secondary Outcome Measures: 1. Cmax: Maximum Observed Plasma Concentration for TAK-994 [ 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 ]
  • 2. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-994 [ 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 ]
  • 3. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-994 [ Time Frame: Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • 4. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-994 [ Time Frame: Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • 5. T1/2z: Terminal Disposition Phase Half-life for TAK-994 [ Time Frame: Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose ]
  • 6. CLR: Renal Clearance for TAK-994 [ 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 ]
  • 7. AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to tau over Dosing Interval for TAK-994 [ 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 ]
  • 8. Part C: Ratio of the Cerebrospinal Fluid (CSF) to plasma AUC From time 0 to 24 hours for TAK-994 [ Time Frame: Day 7 (Part C) Pre-dose and at multiple time points (up to 24 hours) post-dose ]
  • 9. Rac(AUC): Accumulation ratio based on AUCτ for TAK-994 [ 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 ]
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
Criteria

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 =) 18.0 and less than or
equal to (=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 ) 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 and Part F)

8. Has undergone CSF collection within 30 days before check-in (Day -2 [Part C] or Day -1
[Part F]).

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.

Contacts and Locations
Contacts
Locations

United States, California
Parexel International
Glendale

United States, Utah
PRA Health Sciences
Salt Lake City

Sponsors and Collaborators

Takeda

Investigators

Study Director: Medical Director Takeda

More Information
  • Responsible Party: Takeda
  • ClinicalTrials.gov Identifier: NCT03933488 History of Changes
  • Other Study ID Numbers: TAK-994-1001, U1111-1230-8479
  • First Posted: May 1, 2019 Key Record Dates
  • Last Update Posted: June 24, 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 after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach 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.
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Takeda: Drug therapy