A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of TAK-828 Escalating Multiple-Doses in Healthy Participants

• Sponsor: Takeda (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02817516
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 8
• Actual Duration (Months): 1.7
• Patients Per Site Per Month: 13.8

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of multiple oral doses of TAK-828 in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-828; Drug: Placebo	Phase 1

Detailed Description

The drug being tested in this study is called TAK-828. TAK-828 is being tested to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics in healthy non-Japanese and Japanese participants in Parts 1 and 2, respectively.

The study will enroll approximately 56 participants. Participants will be randomly assigned (by chance, like flipping a coin) to receive either TAK-828 or matching placebo. This assignment will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

Proposed doses:

• Part 1: TAK-828 15 mg, 45 mg, 75 mg, 100 mg, and placebo twice daily

• Part 2: TAK-828 45 mg, and 100 mg, and placebo twice daily

All participants will be asked to take the solution at the same time each day throughout the study.

This multi-center trial will be conducted in the United States.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Randomized, Double-Blind (Sponsor-Open), Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Multiple Doses of TAK-828 in Healthy Subjects
• Actual Study Start Date: Jun 30, 2016
• Actual Primary Completion Date: Aug 22, 2016
• Actual Study Completion Date: Aug 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: TAK-828 15 milligram (mg) TAK-828 15 mg, solution (0.2 milligram per milliliter [mg/mL] or 5 mg/mL), orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy non-Japanese participants.	Drug: TAK-828; TAK-828 solution.
Experimental: Part 1: TAK-828 45 mg TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy non-Japanese participants.	Drug: TAK-828; TAK-828 solution.
Experimental: Part 1: TAK-828 75 mg TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy non-Japanese participants.	Drug: TAK-828; TAK-828 solution.
Experimental: Part 1: TAK-828 100 mg TAK-828 100 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy non-Japanese participants.	Drug: TAK-828; TAK-828 solution.
Experimental: Part 2: TAK-828 45 mg TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy Japanese participants.	Drug: TAK-828; TAK-828 solution.
Experimental: Part 2: TAK-828 100 mg TAK-828 100 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy Japanese participants.	Drug: TAK-828; TAK-828 solution.
Placebo Comparator: Part 1: Placebo TAK-828 placebo-matching solution, orally, twice daily on Days 1-13, and once on the morning of Day 14 in healthy non-Japanese participants.	Drug: Placebo; TAK-828 placebo-matching solution.
Placebo Comparator: Part 2: Placebo TAK-828 placebo-matching solution, orally, twice daily on Days 1-14 in healthy Japanese participants.	Drug: Placebo; TAK-828 placebo-matching solution.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) [Baseline up to 10 days after last dose of study drug (Day 24)]

2. Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE) [Baseline up to 10 days after last dose of study drug (Day 24)]

3. Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose [Baseline up to 10 days after last dose of study drug (Day 24)]

4. Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose [Baseline up to 10 days after last dose of study drug (Day 24)]

5. Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) at Least Once Post-dose [Baseline up to 10 days after last dose of study drug (Day 24)]

Secondary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration for Free Base of TAK-828 (TAK-828F) [Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 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-828F [Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose]

3. AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-828F [Cohorts 1 and 2: Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohort 3: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion:

For Parts 1 and 2, participant eligibility is determined according to the following criteria prior to entry into the study:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative, signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.

3. The participant is a healthy male, or a healthy female not of child-bearing potential. Females not of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (example, defined as at least 1 year since last regular menses, with a follicle-stimulating hormone [FSH] level of greater than (>) 40 international units per liter [IU/L] or at least 5 years since last regular menses confirmed before any study drug is administered).

4. For Part 1: the participant is a non-Japanese adult, aged 18 to 55 years (inclusive) at the time of informed consent and first dose of study drug.

5. For Part 1: the participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m^2) (inclusive) at Screening.

6. For Part 2: the participant is of Japanese descent (born to Japanese parents and grandparents), aged 20 to 55 years (inclusive) at the time of informed consent and first dose of study drug.

7. For Part 2: the participant weighs at least 45 kg and has a BMI of 18.5 to 25 kg/m^2 (inclusive) at Screening.

Exclusion Criteria

For Parts 1 and 2, any participant who meets any of the following criteria will not qualify for entry into the study:

1. The participant received any investigational compound within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.

2. The participant used prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) before Check-in (Day -1). Herbal supplements and hormone replacement therapy (HRT) must be discontinued 28 days prior to Check-in (Day -1). As an exception, acetaminophen may be used at doses of less than or equal to (<=) 1 gram/day. Limited use of nonprescription medications that are not believed to affect participant safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.

3. The participant is an immediate family member or study-site employee or is in a dependent relationship with a study-site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.

4. The participant has a history or presence of any disease or condition (or there is any finding upon review of the participant's medical history, physical examination, or clinical laboratory tests giving reasonable suspicion of a disease) that could interfere with study participation or safety, contraindicate taking TAK-828 or a similar drug in the same class, or potentially confound the study results (example, history or presence of clinically significant neurologic, cardiovascular, pulmonary, hepatic, hematologic, renal, immunologic, metabolic, musculoskeletal, gastrointestinal, endocrine, or psychiatric disease). It is the responsibility of the investigator to assess the clinical significance; however, consultation with the Takeda medical monitor may be warranted.

5. The participant has a known hypersensitivity to any component of the formulation of TAK-828.

6. The participant has an active infection at Screening.

7. The participant has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening or Check-in (Day -1).

8. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year, or the participant drinks 7 or more drinks/week for females or 14 or more drinks/week for males (1 drink=5 ounces [150 milliliter ] of wine, 12 ounces [360 mL] of beer, or 1.5 ounces [45 mL] of hard liquor) within 6 months before the Screening visit or is unwilling to abstain from alcohol and drugs throughout the study.

9. The participant is taking or took any excluded medication, supplements, or food products during the time periods listed in the Prohibited Medications, Foods, and Products table

10. If male, the participant intends to donate sperm during the course of this study or for 14 weeks after the last dose of study drug.

11. The participant has any condition possibly affecting drug absorption (example, gastrectomy).

12. The participant has a history of cancer, except basal cell carcinoma that has been in remission for at least 5 years before Screening.

13. The participant has a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody at Screening or has a known history of human immunodeficiency virus (HIV) infection.

14. The participant used nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or nicotine gum) within 28 days prior to Check-in (Day -1) or cotinine test is positive at Screening or Check-in (Day -1).

15. The participant has poor peripheral venous access.

16. The participant donated or lost 450 mL or more of his or her blood volume (including plasmapheresis) or had a transfusion of any blood product within 30 days prior to Day

18. The participant has a Screening or Check-in (Day -1) abnormal (clinically significant) ECG. Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature of the principal investigator or medically qualified subinvestigator.

19. The participant has abnormal Screening or Day -1 laboratory values that suggest a clinically significant underlying disease or the participant has the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN).

20. The participant has a creatine kinase isoenzyme MB (CK-MB) or cardiac troponin above the ULN at Screening or Day -1.

21. If female, the participant is of childbearing potential (example, premenopausal, not sterilized).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Austin	Texas	United States

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02817516
• Other Study ID Numbers: TAK-828-1002; U1111-1177-8105
• First Posted: Jun 29, 2016
• Last Update Posted: Jul 17, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Takeda: Drug Therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 30 June 2016 to 22 August 2016.
Pre-assignment Detail	Non-Japanese healthy participants were enrolled in Part 1 to receive TAK-828 as multiple rising dose of: 15 milligram (mg) in Cohort 1, 45 mg in Cohort 2, and 75 mg in Cohort 3. Study was terminated before the start of 100 mg in Part 1 Cohort 4, and 45 mg and 100 mg in Japanese participants in Part 2 due to findings from 13-week toxicology study.

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 milligram per milliliter [mg/mL] or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Period Title: Overall Study
STARTED	6	6	6	6
COMPLETED	6	6	5	6
NOT COMPLETED	0	0	1	0

Baseline Characteristics

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg	Total
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	Total of all reporting groups
Overall Participants	6	6	6	6	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.2 (7.78)	40.3 (8.45)	26.5 (3.73)	37.0 (14.63)	34.8 (10.27)
Sex: Female, Male (Count of Participants)
Female	1 16.7%	1 16.7%	0 0%	0 0%	2 8.3%
Male	5 83.3%	5 83.3%	6 100%	6 100%	22 91.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 50%	3 50%	4 66.7%	10 41.7%
Not Hispanic or Latino	6 100%	3 50%	3 50%	2 33.3%	14 58.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 16.7%	1 16.7%	0 0%	0 0%	2 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 50%	0 0%	1 16.7%	0 0%	4 16.7%
White	2 33.3%	5 83.3%	3 50%	6 100%	16 66.7%
More than one race	0 0%	0 0%	2 33.3%	0 0%	2 8.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%	6 100%	6 100%	6 100%	24 100%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	172.3 (11.72)	171.8 (9.15)	175.3 (2.42)	168.5 (3.94)	172.0 (7.67)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	77.75 (15.209)	72.23 (6.696)	77.45 (9.702)	73.45 (11.232)	75.22 (10.679)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	25.97 (2.645)	24.48 (1.525)	25.17 (2.743)	25.87 (3.974)	25.37 (2.733)
Smoking Classification (Count of Participants)
Never smoked	5 83.3%	5 83.3%	5 83.3%	4 66.7%	19 79.2%
Ex-smoker	1 16.7%	1 16.7%	1 16.7%	2 33.3%	5 20.8%
Alcohol Classification (Count of Participants)
Never drunk	5 83.3%	2 33.3%	3 50%	3 50%	13 54.2%
Current drinker	1 16.7%	2 33.3%	2 33.3%	2 33.3%	7 29.2%
Ex-drinker	0 0%	2 33.3%	1 16.7%	1 16.7%	4 16.7%
Caffeine/Xanthine Consumption (Count of Participants)
Had caffeine/xanthine consumption	1 16.7%	2 33.3%	2 33.3%	4 66.7%	9 37.5%
Had no caffeine/xanthine consumption	5 83.3%	4 66.7%	4 66.7%	2 33.3%	15 62.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Time Frame	Baseline up to 10 days after last dose of study drug (Day 24)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6	6
Number [percentage of participants]	16.7 278.3%	33.3 555%	50.0 833.3%	16.7 278.3%

2. Primary Outcome

Title	Percentage of Participants Who Discontinued the Treatment Due to an Adverse Event (AE)
Time Frame	Baseline up to 10 days after last dose of study drug (Day 24)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6	6
Number [percentage of participants]	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose
Time Frame	Baseline up to 10 days after last dose of study drug (Day 24)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6	6
Number [percentage of participants]	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose
Time Frame	Baseline up to 10 days after last dose of study drug (Day 24)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6	6
Systolic blood pressure (BP) supine <85 mmHg	0 0%	16.7 278.3%	0 0%	0 0%
Systolic BP standing<85millimeter of mercury(mmHg)	16.7 278.3%	0 0%	0 0%	0 0%
Diastolic BP supine less than (<) 50 mm Hg	0 0%	16.7 278.3%	0 0%	0 0%
Diastolic BP standing <50 mm Hg	0 0%	0 0%	16.7 278.3%	0 0%
Pulse rate supine <50 beats per minute (bpm)	16.7 278.3%	0 0%	0 0%	0 0%
Pulse rate 5 minutes supine <50 bpm	16.7 278.3%	33.3 555%	50.0 833.3%	50.0 833.3%
Pulse rate 1 minute standing <50 bpm	16.7 278.3%	0 0%	0 0%	0 0%
Pulse rate 3 minute standing <50 bpm	16.7 278.3%	0 0%	0 0%	0 0%
Pulse rate 3 minute standing greater than 120 bpm	0 0%	16.7 278.3%	0 0%	0 0%
Temperature <35.6 Celsius	0 0%	0 0%	33.3 555%	33.3 555%

5. Primary Outcome

Title	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) at Least Once Post-dose
Time Frame	Baseline up to 10 days after last dose of study drug (Day 24)

Outcome Measure Data

Analysis Population Description

The safety set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6	6
Heart Rate <50 bpm	16.7 278.3%	33.3 555%	33.3 555%	50.0 833.3%
QT Interval greater than or equalto 460millisecond	16.7 278.3%	0 0%	16.7 278.3%	0 0%

6. Secondary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Free Base of TAK-828 (TAK-828F)
Time Frame	Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) set included all participants who received at least 1 dose of study drug, had at least 1 measurable plasma/urine concentration of TAK-828F. PK set where data at specified time points was available. PK data was not collected for Day 7 and 14 Part 1 Cohort 3, as participants received last dose on Day 6 due to study termination.

Arm/Group Title	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6
Day 1	1170 (302)	3750 (562)	9680 (1580)
Day 7	1480 (230)	4610 (619)
Day 14	1310 (345)	4600 (524)

7. Secondary Outcome

Title	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-828F
Time Frame	Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description

PK set included all participants who received at least 1 dose of study drug, had at least 1 measurable plasma/urine concentration of TAK-828F. PK set where data at specified time points was available. PK data was not collected for Day 7 and 14 Part 1 Cohort 3, as participants received last dose on Day 6 due to study termination.

Arm/Group Title	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6
Day 1	1.0	1.0	1.0
Day 7	1.0	0.5
Day 14	1.0	0.5

8. Secondary Outcome

Title	AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for TAK-828F
Time Frame	Cohorts 1 and 2: Days 1 and 7 pre-dose and at multiple time points (up to 24 hours) post-dose and Day 14 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohort 3: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

Outcome Measure Data

Analysis Population Description

PK set included all participants who received at least 1 dose of study drug, had at least 1 measurable plasma/urine concentration of TAK-828F. PK set where data at specified time points was available. PK data was not collected for Day 7 and 14 Part 1 Cohort 3, as participants received last dose on Day 6 due to study termination.

Arm/Group Title	Part 1 Cohort 1: TAK-828 15 mg	Part 1 Cohort 2: TAK-828 45 mg	Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.	TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
Measure Participants	6	6	6
Day 1	5090 (1300)	15400 (1360)	40000 (5870)
Day 7	6730 (1320)	17900 (3060)
Day 14	6890 (1540)	20600 (3860)

Adverse Events

Time Frame	TEAEs are adverse events that started after the first dose of double-blind study drug and no more than 10 days (Day 24) after the last dose of double-blind study drug
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Part 1 Cohorts 1 to 3: Placebo		Part 1 Cohort 1: TAK-828 15 mg		Part 1 Cohort 2: TAK-828 45 mg		Part 1 Cohort 3: TAK-828 75 mg
Arm/Group Description	TAK-828 placebo-matching solution, orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.		TAK-828 15 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.		TAK-828 45 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.		TAK-828 75 mg, solution (0.2 mg/mL or 5 mg/mL), orally, twice daily on Days 1 to 13, and once in the morning of Day 14 in healthy non-Japanese participants.
All Cause Mortality
	Part 1 Cohorts 1 to 3: Placebo		Part 1 Cohort 1: TAK-828 15 mg		Part 1 Cohort 2: TAK-828 45 mg		Part 1 Cohort 3: TAK-828 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	Part 1 Cohorts 1 to 3: Placebo		Part 1 Cohort 1: TAK-828 15 mg		Part 1 Cohort 2: TAK-828 45 mg		Part 1 Cohort 3: TAK-828 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Part 1 Cohorts 1 to 3: Placebo		Part 1 Cohort 1: TAK-828 15 mg		Part 1 Cohort 2: TAK-828 45 mg		Part 1 Cohort 3: TAK-828 75 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		2/6 (33.3%)		3/6 (50%)		1/6 (16.7%)
Eye disorders
Dry eye	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Gastrointestinal disorders
Nausea	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Frequent bowel movements	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Infections and infestations
Upper respiratory tract infection	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Muscle twitching	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Myalgia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Pain in extremity	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Nervous system disorders
Headache	0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)
Dizziness postural	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Syncope	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Dizziness	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Psychiatric disorders
Insomnia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.