Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of TAK-828 in Healthy Participants

A Randomized, Double-Blind (Sponsor-Open), Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single Doses of TAK-828 in Healthy Non-Japanese and Japanese Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02706834

Enrollment

Registered

2016-03-11

Start date

2016-03-01

Completion date

2016-06-17

Last updated

2018-10-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dose Finding Study

Keywords

Drug therapy

Brief summary

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

Detailed description

The drug being tested in this study is called TAK-828. TAK-828 is being tested to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single oral doses of TAK-828 in healthy non-Japanese and Japanese participants. The study enrolled 36 healthy participants. An interleaving crossover design with placebo substitution was used for Cohorts 1 and 2, and a crossover design was used in Cohort 3. Each cohort consisted of 12 participants, and participants were randomized to treatment sequence to receive TAK-828 or placebo after undergoing a fasting stage of at least 8 hours through intervention periods 1-4 for Cohorts 1 and 2 and through intervention periods 1 - 3 for Cohort 3. The assigned treatment sequence will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need). An additional interventional period 5 (fed state) is planned to be conducted in either cohort 1 or 2, based on the dose of TAK-828 that will be chosen to be studied under fed conditions. Cohorts 1 and 2 were conducted in non-Japanese participants and Cohort 3 in Japanese participants. This multi-center trial was conducted in the United States. Participants remained confined to the study site from check-in (Day -1) through Day 4 of each intervention period and returned 7 to 10 days after last dose of study drug for a follow-up assessment.

Interventions

DRUGTAK-828

TAK-828 oral solution

DRUGPlacebo

TAK-828 placebo-matching oral solution

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

- 1. Is a healthy male and female (non-child bearing potential) participants. 2. Cohorts 1 and 2: non-Japanese participants aged 18 to 55 years, inclusive, with body mass index (BMI) of 18 to 30 kilogram per square meter (kg/m\^ 2), inclusive, and body weight greater than or equal (\>=) 50 kilograms (kg). 3. Cohort 3: Japanese participants (born to Japanese parents and grandparents) aged 20 to 55 years, inclusive, with BMI of 18.5 to 25 kg/m\^ 2, inclusive, and body weight \>= 45 kg.

Exclusion criteria

- 1\. Has used prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to 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 equal to (\<=) 1 gram per day (g/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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Day 1 up to 7 days after last dose of study drug (up to 52 days)	Heart Rate \<50 beats per minute (bpm) \>120 bpm; QTcB (Bazett's Correction Formula) ≤50 milliseconds (msec) or ≥500 msec OR ≥30 msec change from Baseline and ≥450 msec; QTcF (Fridericia's Correction Formula) ≤50 msec or ≥500 msec OR ≥30 msec change from Baseline (CFB) and ≥450 msec.
Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	Day 1 up to 30 days after last dose of study drug (up to 85 days)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	Day 1 up to 30 days after last dose of study drug (up to 85 days)	—
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	Day 1 up to 7 days after last dose of study drug (up to 52 days)	Hematology and Chemistry values that met the following criteria were considered to be markedly abnormal: Erythrocytes, Hematocrit and Hemoglobin \<0.8\Lower Limit of Normal (LLN) or \>1.2\Upper Limit of Normal ULN.; Leukocytes \<0.5\LLN or \>1.5\ULN; Platelet \<75 or \>600 10\^9/liter (L). Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase \>3\ULN; Albumin \<25 g/L; Bilirubin \> 34.2 umol/L; Blood Urea Nitrogen \>10.7 mmol/L; Chloride \<75 or \>126 mmol/L; Creatinine \>177 umol/L; Direct Bilirubin \>2\ULN; Glucose \<2.8 or \>19.4 mmol/L; Potassium \<3.0 or \>6.0 mmol/L; Protein \<0.8\LLN or \>1.2\ULN; Sodium \<130 or \>150 mmol/L.
Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Day 1 up to 7 days after last dose of study drug (up to 52 days)	Vital signs measurements that met the following criteria were considered to be markedly abnormal: Systolic Blood Pressure (SBP) \<85 mmHg or \>180 mmHg supine laying face upward) or standing; Diastolic Blood Pressure (DBP) \<50 mmHg or \>110 mmHg supine or standing; Pulse Rate (PR) \<50 beats/minute (bpm) or \>120 bpm supine or standing; Temperature \<35.6 degrees Celsius (C) or \>37.7 degrees C.

Secondary

Measure	Time frame
Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose
t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose
AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Countries

United States

Participant flow

Recruitment details

Participants took part in the study at 2 investigative sites in the United States from 01 March 2016 to 17 June 2016.

Pre-assignment details

Non-Japanese healthy participants were randomized to Cohort 1 or Cohort 2 with 4 different sequences to receive TAK-828 or placebo in a ratio of 9:3. Japanese healthy participants were randomized into Cohort 3 with 3 different sequences to receive TAK-828 or placebo in a ratio of 8:4.

Participants by arm

Arm	Count
Cohort 1, Sequence I Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 1, Sequence II Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 1, Sequence III Non-Japanese participants. TAK-828 0.1 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 1, Sequence IV Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 0.5 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 15 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 2, Sequence I Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 2, Sequence II Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 2, Sequence III Non-Japanese participants. TAK-828 3 mg, oral solution, fasted (after an 8 hour fast) on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 2, Sequence IV Non-Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 50 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 200 mg, oral solution, fasted, on Day 1 of Period 3; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 4; followed by, TAK-828 100 mg, oral solution, fed (high-fat, high-calorie meal 30 minutes prior to administration of study drug), on Day 1 of Period 5. There was a 7-day washout period between each period. Each period lasted 4 days with a 7-day washout period between periods.	3
Cohort 3, Sequence I Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods.	4
Cohort 3, Sequence II Japanese participants. TAK-828 15 mg, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, placebo-matching TAK-828, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods.	4
Cohort 3, Sequence III Japanese participants. Placebo-matching TAK-828, oral solution, fasted (after an 8 hour fast), on Day 1 of Period 1; followed by, TAK-828 100 mg, oral solution, fasted, on Day 1 of Period 2; followed by, TAK-828 150 mg, oral solution, fasted, on Day 1 of Period 3. Each period lasted 4 days with a 7-day washout period between periods.	4
Total	36

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG004	FG009	FG010
Overall Study	Lost to Follow-up	0	0	1	0	0	0
Overall Study	Other Reason Not Specified	1	0	0	1	0	0
Overall Study	Pretreatment Event/Adverse Event	0	1	0	0	0	1
Overall Study	Voluntary Withdrawal	1	0	0	0	1	0

Baseline characteristics

Characteristic	Cohort 1, Sequence II	Total	Cohort 3, Sequence III	Cohort 3, Sequence II	Cohort 3, Sequence I	Cohort 2, Sequence IV	Cohort 2, Sequence III	Cohort 1, Sequence I	Cohort 2, Sequence II	Cohort 2, Sequence I	Cohort 1, Sequence IV	Cohort 1, Sequence III
Age, Continuous	29.3 years STANDARD_DEVIATION 11.68	35.9 years STANDARD_DEVIATION 8.45	43.8 years STANDARD_DEVIATION 5.44	34.3 years STANDARD_DEVIATION 6.65	37.5 years STANDARD_DEVIATION 10.02	40.7 years STANDARD_DEVIATION 5.51	32.3 years STANDARD_DEVIATION 10.69	34.3 years STANDARD_DEVIATION 10.26	40.3 years STANDARD_DEVIATION 8.39	28.0 years STANDARD_DEVIATION 6.24	36.7 years STANDARD_DEVIATION 9.71	34.7 years STANDARD_DEVIATION 4.16
Alcohol Classification Current Drinker	0 participants	11 participants	2 participants	0 participants	2 participants	0 participants	1 participants	2 participants	1 participants	0 participants	2 participants	1 participants
Alcohol Classification Ex-drinker	1 participants	8 participants	1 participants	1 participants	0 participants	0 participants	1 participants	0 participants	1 participants	2 participants	1 participants	0 participants
Alcohol Classification Missing	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants
Alcohol Classification Never Drunk	2 participants	16 participants	1 participants	3 participants	2 participants	3 participants	1 participants	0 participants	1 participants	1 participants	0 participants	2 participants
Body Mass Index (BMI)	27.41 kg/m^2 STANDARD_DEVIATION 0.755	25.01 kg/m^2 STANDARD_DEVIATION 2.584	23.20 kg/m^2 STANDARD_DEVIATION 1.622	22.96 kg/m^2 STANDARD_DEVIATION 0.527	22.05 kg/m^2 STANDARD_DEVIATION 1.864	26.37 kg/m^2 STANDARD_DEVIATION 3.709	25.73 kg/m^2 STANDARD_DEVIATION 3.17	26.28 kg/m^2 STANDARD_DEVIATION 1.828	24.25 kg/m^2 STANDARD_DEVIATION 1.772	26.34 kg/m^2 STANDARD_DEVIATION 3.071	26.65 kg/m^2 STANDARD_DEVIATION 2.727	26.08 kg/m^2 STANDARD_DEVIATION 1.765
Female Reproductive Status Female of Childbearing Potential	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Female Reproductive Status N/A (Participant is Male)	3 participants	34 participants	4 participants	4 participants	4 participants	3 participants	3 participants	3 participants	2 participants	2 participants	3 participants	3 participants
Female Reproductive Status Postmenopausal	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants
Female Reproductive Status Surgically Sterile	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Height	176.3 cm STANDARD_DEVIATION 2.89	172.9 cm STANDARD_DEVIATION 6.82	173.0 cm STANDARD_DEVIATION 8.64	168.5 cm STANDARD_DEVIATION 5	174.3 cm STANDARD_DEVIATION 6.24	170.3 cm STANDARD_DEVIATION 7.23	178.0 cm STANDARD_DEVIATION 4.36	176.3 cm STANDARD_DEVIATION 3.21	166.1 cm STANDARD_DEVIATION 9.54	169.7 cm STANDARD_DEVIATION 12.5	176.7 cm STANDARD_DEVIATION 1.53	173.3 cm STANDARD_DEVIATION 5.69
Race/Ethnicity, Customized Asian	0 participants	13 participants	4 participants	4 participants	4 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Race/Ethnicity, Customized Black or African American	1 participants	6 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants	0 participants	0 participants	1 participants	2 participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants	5 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants	2 participants	1 participants	0 participants	0 participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 participants	31 participants	4 participants	4 participants	4 participants	2 participants	3 participants	2 participants	1 participants	2 participants	3 participants	3 participants
Race/Ethnicity, Customized White	2 participants	17 participants	0 participants	0 participants	0 participants	2 participants	3 participants	2 participants	3 participants	2 participants	2 participants	1 participants
Region of Enrollment United States	3 participants	36 participants	4 participants	4 participants	4 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants
Sex: Female, Male Female	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Sex: Female, Male Male	3 Participants	34 Participants	4 Participants	4 Participants	4 Participants	3 Participants	3 Participants	3 Participants	2 Participants	2 Participants	3 Participants	3 Participants
Smoking Classification Current Smoker	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Smoking Classification Ex-smoker	0 participants	3 participants	1 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants
Smoking Classification Never Smoked	3 participants	33 participants	3 participants	4 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	3 participants	2 participants
Weight	85.23 kg STANDARD_DEVIATION 2.686	74.93 kg STANDARD_DEVIATION 10.416	69.88 kg STANDARD_DEVIATION 10.806	65.18 kg STANDARD_DEVIATION 3.149	66.73 kg STANDARD_DEVIATION 1.563	77.13 kg STANDARD_DEVIATION 16.354	81.63 kg STANDARD_DEVIATION 11.946	81.87 kg STANDARD_DEVIATION 8.686	66.87 kg STANDARD_DEVIATION 8.135	75.53 kg STANDARD_DEVIATION 8.173	83.23 kg STANDARD_DEVIATION 9.16	78.60 kg STANDARD_DEVIATION 9.569
Xanthine/Caffeine Consumption No	1 participants	11 participants	0 participants	2 participants	1 participants	2 participants	1 participants	0 participants	1 participants	1 participants	1 participants	1 participants
Xanthine/Caffeine Consumption Yes	2 participants	25 participants	4 participants	2 participants	3 participants	1 participants	2 participants	3 participants	2 participants	2 participants	2 participants	2 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	3 / 10	5 / 9	3 / 8	1 / 7	0 / 7	1 / 8	0 / 9	1 / 9	1 / 9	1 / 9	2 / 9	0 / 4	0 / 12	2 / 8	6 / 8	4 / 6
serious Total, serious adverse events	0 / 10	1 / 9	0 / 8	0 / 7	0 / 7	0 / 8	0 / 9	0 / 9	0 / 9	0 / 9	0 / 9	0 / 4	0 / 12	0 / 8	0 / 8	0 / 6

Outcome results

Primary

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Time frame: Day 1 up to 30 days after last dose of study drug (up to 85 days)

Population: Safety Set included all participants who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Cohort 1: Placebo	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	11.1 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	12.5 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)	0 percentage of participants

Primary

Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Time frame: Day 1 up to 30 days after last dose of study drug (up to 85 days)

Population: Safety Set included all participants who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Cohort 1: Placebo	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	30.0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	55.6 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	37.5 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	14.3 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	12.5 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	11.1 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	11.1 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	11.1 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	22.2 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	25.0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	75.0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)	66.7 percentage of participants

Primary

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose

Heart Rate \<50 beats per minute (bpm) \>120 bpm; QTcB (Bazett's Correction Formula) ≤50 milliseconds (msec) or ≥500 msec OR ≥30 msec change from Baseline and ≥450 msec; QTcF (Fridericia's Correction Formula) ≤50 msec or ≥500 msec OR ≥30 msec change from Baseline (CFB) and ≥450 msec.

Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days)

Population: Safety Set included all participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (NUMBER)
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	20.0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	33.3 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	25.0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	28.6 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	25.0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	25.0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	44.4 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	33.3 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	33.3 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	33.3 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	55.6 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	50.0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	8.3 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	8.3 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	12.5 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	12.5 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	QTcB: ≥500 msec OR ≥30 msec CFB and ≥450 msec	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose	Heart Rate <50 bpm	0 percentage of participants

Primary

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose

Hematology and Chemistry values that met the following criteria were considered to be markedly abnormal: Erythrocytes, Hematocrit and Hemoglobin \<0.8\*Lower Limit of Normal (LLN) or \>1.2\*Upper Limit of Normal ULN.; Leukocytes \<0.5\*LLN or \>1.5\*ULN; Platelet \<75 or \>600 10\^9/liter (L). Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase \>3\*ULN; Albumin \<25 g/L; Bilirubin \> 34.2 umol/L; Blood Urea Nitrogen \>10.7 mmol/L; Chloride \<75 or \>126 mmol/L; Creatinine \>177 umol/L; Direct Bilirubin \>2\*ULN; Glucose \<2.8 or \>19.4 mmol/L; Potassium \<3.0 or \>6.0 mmol/L; Protein \<0.8\*LLN or \>1.2\*ULN; Sodium \<130 or \>150 mmol/L.

Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days)

Population: Safety Set included all participants who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose	0 percentage of participants

Primary

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose

Vital signs measurements that met the following criteria were considered to be markedly abnormal: Systolic Blood Pressure (SBP) \<85 mmHg or \>180 mmHg supine laying face upward) or standing; Diastolic Blood Pressure (DBP) \<50 mmHg or \>110 mmHg supine or standing; Pulse Rate (PR) \<50 beats/minute (bpm) or \>120 bpm supine or standing; Temperature \<35.6 degrees Celsius (C) or \>37.7 degrees C.

Time frame: Day 1 up to 7 days after last dose of study drug (up to 52 days)

Population: Safety Set included all participants who received at least 1 dose of study drug.

Arm	Measure	Group	Value (NUMBER)
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	20.0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	10.0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	20.0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	20.0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	20.0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 1: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	10.0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	11.1 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	22.2 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	11.1 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	11.1 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	11.1 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 0.1 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	22.2 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	25.0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	25.0 percentage of participants
Cohort 1: TAK-828 0.5 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	14.3 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	14.3 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	28.6 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	14.3 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	14.3 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	25.0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	12.5 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	12.5 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	12.5 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	12.5 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 1: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	11.1 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	11.1 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	11.1 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	11.1 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	33.3 percentage of participants
Cohort 2: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	11.1 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	11.1 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	22.2 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 3 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	11.1 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	11.1 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	22.2 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	11.1 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 50 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	22.2 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 200 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	11.1 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	11.1 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	22.2 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	50.0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 2: TAK-828 100 mg/ Fed	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	8.3 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	8.3 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	0 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	8.3 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	16.7 percentage of participants
Cohort 3: Placebo	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 15 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	12.5 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	0 percentage of participants
Cohort 3: TAK-828 100 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	12.5 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: standing, after 3 minutes	16.7 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 3 minutes	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	DBP <50 mmHg: supine, after 5 minutes	16.7 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR >120 bpm: standing, after 1 minute	0 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	PR <50 bpm: supine, after 5 minutes	16.7 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	Temperature: <35.6 C	16.7 percentage of participants
Cohort 3: TAK-828 150 mg/ Fasted	Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose	SBP <85 mmHg: standing, after 3 minutes	0 percentage of participants

Secondary

AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)

Time frame: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Population: PK Set included participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F.Food effect statistical analysis is based on 10 participants who received TAK-828 100 mg fasted and fed.AUC∞ was not calculated for TAK-828 0.1 mg arm due to lack of well-defined terminal elimination phase.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: TAK-828 0.1 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	214 ng*h/mL	Standard Deviation 30.4
Cohort 1: TAK-828 0.5 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	1150 ng*h/mL	Standard Deviation 211
Cohort 1: TAK-828 15 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	5930 ng*h/mL	Standard Deviation 1430
Cohort 1: TAK-828 100 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	23100 ng*h/mL	Standard Deviation 5400
Cohort 1: TAK-828 100 mg/ Fed	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	45400 ng*h/mL	Standard Deviation 10300
Cohort 2: Placebo	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	38000 ng*h/mL	Standard Deviation 7370
Cohort 2: TAK-828 3 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	106000 ng*h/mL	Standard Deviation 20800
Cohort 2: TAK-828 50 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	8560 ng*h/mL	Standard Deviation 1610
Cohort 2: TAK-828 200 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	54600 ng*h/mL	Standard Deviation 13400
Cohort 2: TAK-828 100 mg/ Fasted	AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)	83700 ng*h/mL	Standard Deviation 16400

Comparison: Food Effect: A linear mixed effect model on the natural log (ln)-transformed parameters was performed with dosing condition as a fixed effect and participant as a random effect using the Kenward-Roger estimation for computing the denominator degrees of freedom. The least squares means and difference of least squared means for the ln-transformed parameters were exponentiated to obtain the geometric means and ratios of geometric means on the original scale.90% CI: [0.833, 0.964]

Secondary

Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)

Time frame: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F. Food effect statistical analysis is based on 10 participants who received TAK-828 100 mg under fasted and fed conditions.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: Placebo	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	5.96 ng/mL	Standard Deviation 0.982
Cohort 1: TAK-828 0.1 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	38.6 ng/mL	Standard Deviation 3.56
Cohort 1: TAK-828 0.5 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	247 ng/mL	Standard Deviation 28.7
Cohort 1: TAK-828 15 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	1150 ng/mL	Standard Deviation 201
Cohort 1: TAK-828 100 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	4820 ng/mL	Standard Deviation 1090
Cohort 1: TAK-828 100 mg/ Fed	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	8900 ng/mL	Standard Deviation 1870
Cohort 2: Placebo	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	3730 ng/mL	Standard Deviation 850
Cohort 2: TAK-828 3 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	18400 ng/mL	Standard Deviation 2950
Cohort 2: TAK-828 50 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	1400 ng/mL	Standard Deviation 114
Cohort 2: TAK-828 200 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	9530 ng/mL	Standard Deviation 1030
Cohort 2: TAK-828 100 mg/ Fasted	Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)	14300 ng/mL	Standard Deviation 2470

Secondary

t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)

Time frame: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F. T1/2z was not calculated for the TAK-828 0.1 mg arm because Lambda z, required for the calculation, was not calculated due to the lack of a well-defined terminal elimination phase.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1: TAK-828 0.1 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	5.38 h	Standard Deviation 0.568
Cohort 1: TAK-828 0.5 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	4.94 h	Standard Deviation 1.11
Cohort 1: TAK-828 15 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	6.53 h	Standard Deviation 1.14
Cohort 1: TAK-828 100 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	7.51 h	Standard Deviation 1.95
Cohort 1: TAK-828 100 mg/ Fed	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	7.53 h	Standard Deviation 1.32
Cohort 2: Placebo	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	7.04 h	Standard Deviation 0.701
Cohort 2: TAK-828 3 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	7.97 h	Standard Deviation 1.42
Cohort 2: TAK-828 50 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	6.71 h	Standard Deviation 1.37
Cohort 2: TAK-828 200 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	6.71 h	Standard Deviation 0.95
Cohort 2: TAK-828 100 mg/ Fasted	t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)	6.44 h	Standard Deviation 0.406

Secondary

Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)

Time frame: Day 1 pre-dose and at multiple timepoints (up to 72 hours) post-dose

Population: Pharmacokinetic (PK) Set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma or urine concentration of TAK-828F.

Arm	Measure	Value (MEDIAN)
Cohort 1: Placebo	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 1: TAK-828 0.1 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 1: TAK-828 0.5 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 1: TAK-828 15 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 1: TAK-828 100 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 1: TAK-828 100 mg/ Fed	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 2: Placebo	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	3.50 hours (h)
Cohort 2: TAK-828 3 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 2: TAK-828 50 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 2: TAK-828 200 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)
Cohort 2: TAK-828 100 mg/ Fasted	Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)	1.00 hours (h)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of TAK-828 in Healthy Participants

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event (TEAE)

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Measurements at Least Once Post-dose

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post-dose

Percentage of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post-dose

AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity Calculated Using the Observed Value of the Last Quantifiable Concentration for TAK-828F (Free Base of TAK-828)

Cmax: Maximum Observed Plasma Concentration for TAK-828F (Free Base of TAK-828)

t1/2z: Terminal Disposition Phase Half-Life for TAK-828F (Free Base of TAK-828)

Tmax: Time of First Occurrence of Cmax for TAK-828F (Free Base of TAK-828)