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

NCT04082481 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: TAK-988-1001U1111-1238-5474
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy Volunteers

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (4)

• Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs)

  Baseline up to Day 26

• Number of Participants With at Least one Markedly Abnormal Value (MAV) for Laboratory Values

  Baseline up to Day 26

• Number of Participants With at Least one MAV for Vital Signs

  Baseline up to Day 26

• Number of Participants With at Least one MAV for Electrocardiograms (ECGs)

  Baseline up to Day 26

Secondary Outcomes (9)

• Cmax: Maximum Observed Plasma Concentration for TAK-988

  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

  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

  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

  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

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

Study Arms (5)

TAK-988: Part A

EXPERIMENTAL

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.

Drug: TAK-988; Drug: TAK-988 Placebo

TAK-988: Part B

EXPERIMENTAL

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.

Drug: TAK-988; Drug: TAK-988 Placebo

TAK-988: Part C

EXPERIMENTAL

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.

Drug: TAK-988; Drug: TAK-988 Placebo

TAK-988: Part D

EXPERIMENTAL

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.

Drug: TAK-988; Drug: TAK-988 Placebo

TAK-988: Part E

EXPERIMENTAL

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.

Drug: TAK-988; Drug: TAK-988 Placebo

Interventions

TAK-988 DRUG

TAK-988 tablets.

TAK-988: Part A; TAK-988: Part B; TAK-988: Part C; TAK-988: Part D; TAK-988: Part E

TAK-988 Placebo DRUG

TAK-988 placebo-matching tablets.

TAK-988: Part A; TAK-988: Part B; TAK-988: Part C; TAK-988: Part D; TAK-988: 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)
• 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)
• 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-988 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)
• Has undergone CSF collection within 30 days before check-in (Day -2).
• 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 Internalional - Glendale

Glendale, California, 91206, United States

Location

PRA Health Sciences - Salt Lake City

Millcreek, Utah, 84124, 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: September 5, 2019
• First Posted: September 9, 2019
• Study Start: November 17, 2021
• Primary Completion: April 29, 2022
• Study Completion: April 29, 2022
• Last Updated: November 26, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share

Locations

US (2)