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

NCT03933488 | Completed Phase 1 FDA Drug

• 2 other identifiers: TAK-994-1001U1111-1230-8479
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Participants

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)

  Baseline up to Day 26

• Number of Participants With at Least one Markedly Abnormal Laboratory Value

  Baseline up to Day 26

• Number of Participants With at Least one Markedly Abnormal Laboratory Value for Vital Signs

  Baseline up to Day 26

• Number of Participants With at Least one Markedly Abnormal Laboratory Value for Electrocardiogram (ECG)

  Baseline up to Day 26

Secondary Outcomes (9)

• Cmax: Maximum Observed Plasma Concentration for TAK-994

  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-994

  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-994

  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-994

  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-994

  Day 1 (Parts A-E) pre-dose and at multiple time points (up to 72 hours) post-dose

Study Arms (5)

TAK-994: Part A

EXPERIMENTAL

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; Drug: TAK-994 Placebo

TAK-994: Part B

EXPERIMENTAL

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; Drug: TAK-994 Placebo

TAK-994: Part C

EXPERIMENTAL

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; Drug: TAK-994 Placebo

TAK-994: Part D

EXPERIMENTAL

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; Drug: TAK-994 Placebo

TAK-994: Part E

EXPERIMENTAL

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; Drug: TAK-994 Placebo

Interventions

TAK-994 DRUG

TAK-994 tablets.

TAK-994: Part A; TAK-994: Part B; TAK-994: Part C; TAK-994: Part D; TAK-994: Part E

TAK-994 Placebo DRUG

TAK-994 placebo-matching tablets.

TAK-994: Part A; TAK-994: Part B; TAK-994: Part C; TAK-994: Part D; TAK-994: Part E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 and Part F)
• 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, C, and F)
• Must be aged 18 to 55 years, inclusive, at the screening visit.
• Must have a body weight \>=50 kilogram (kg) at the screening visit.
• HE Participants (Part D)
• Must be aged \>=65 years, inclusive, at the time of informed consent.
• Must have a body weight \>=40 kg at the screening visit.
• Healthy Japanese Adult Participants (Part E)
• Must be aged 18 to 55 years, inclusive, at the screening visit.
• Must have a BMI \>=18.0 and \<=26.0 kg/m\^2 at the screening visit.
• Must have been born in Japan to a Japanese mother and father and have maternal and paternal Japanese grandparents.
• Must have not been away from Japan for more than 10 years at the screening visit.
• In the opinion of the investigator, must have a lifestyle that has not changed significantly since relocation from Japan.

You may not qualify if:

• Has a known hypersensitivity to any component of the formulation of TAK-994 or related compounds.
• 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.
• 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.
• Has a clinically significant history of head injury or head trauma.
• Has a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
• Screening electrocardiogram (ECG) reveals a QT interval with the Fridericia's correction method (QTcF) greater than (\>) 450 millisecond (ms) (men) or \>470 ms (women).
• 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)
• Has undergone CSF collection within 30 days before check-in (Day -2 \[Part C\] or Day -1 \[Part F\]).
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Parexel International

Glendale, California, 91206, United States

Location

PRA Health Sciences

Salt Lake City, Utah, 84125, United States

Location

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 1, 2019
• Study Start: May 1, 2019
• Primary Completion: March 29, 2020
• Study Completion: March 29, 2020
• Last Updated: June 24, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)