Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-831 when administered as single or multiple oral doses in healthy adult Asian participants.
Detailed description
The drug being tested in this study is called TAK-831. This study will assess the safety, tolerability, pharmacokinetics (PK), and Pharmacodynamics (PD) of TAK-831 when administered as single or multiple oral doses in healthy adult Asian participants (Japanese and Chinese participants). The study will enroll approximately 40 participants and include up to 5 cohorts of healthy adult Japanese or Chinese participants as following (8 participants per a cohort). Cohorts 3, 4 and 5 are optional and will be decided to run based on the data of Cohorts 1 and 2. Dose level for these cohorts will be defined based on the result of Cohort 1 or Cohort 2. * Japanese Cohort 1-A; TAK-831 100 mg single dose + TAK-831 300 mg single dose * Japanese Cohort 1-B; TAK-831 100 mg single dose + Placebo single dose * Japanese Cohort 1-C; Placebo single dose + TAK-831 300 mg single dose * Japanese Cohort 2; TAK-831 300 mg or TAK-831 matching placebo, single dose + TAK-831 300 mg or TAK-831 matching placebo, multiple dose \* * Chinese Cohort 3; TAK-831 600 mg or TAK-831 matching placebo, single dose + TAK-831 600 mg or TAK-831 matching placebo, multiple dose * Japanese Cohort 4; TAK-831 600 mg or TAK-831 matching placebo, single dose + TAK-831 600 mg or TAK-831 matching placebo, multiple dose * Japanese Cohort 5; TAK-831 50 mg or TAK-831 matching placebo, single dose + TAK-831 50 mg or TAK-831 matching placebo, multiple dose \*The dose in Cohort 2 will be adjusted based on the safety and tolerability as well as PK and PD in Cohort 1. Above all treatment, randomization information will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need) and TAK-831 will be administered orally. This single center trial will be conducted in Japan. The overall time to participate in Cohort 1 of this study is approximately 12 days and 19 days in Cohorts 2 to 5. 11 days (for Cohort 1) or 12 days (for Cohorts 2 to 5) after last dose of study drug, participants will be contacted by telephone for a follow-up assessment unless abnormal, clinically significant findings are observed upon discharge.
Interventions
DRUGTAK-831
TAK-831 Tablets.
DRUGPlacebo
TAK-831 Matching Placebo Tablets.
Sponsors
Takeda
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. The participant must understand the study procedures and agree to participate by providing written informed consent (for Chinese participants, an interpreter should be present as necessary). 2. The participant must be willing and able to comply with all study procedures and restrictions. 3. The participant must be male or female (of nonchildbearing potential) aged 20 to 55 years, inclusive, at the Screening. 4. The participant must have a body mass index (BMI) \>=18.5 kg/m\^2 and =\<25.0 kg/m\^2 at the Screening. 5. The participant must be a current nonsmoker who has not used tobacco- or nicotine-containing products (e.g., nicotine patch) for at least 6 months prior to the Screening. 6. Chinese participants are defined as participants who were born in mainland China, and their biological parents and grandparents must all have been of Chinese origin (for Cohort 3 only). 7. Chinese participants who have lived out of China for more than 5 years must not have significantly modified their diets since leaving China (for Cohort 3 only). 8. The participant must be judged to be in good health by the investigator, based on clinical evaluations including laboratory tests, medical history, full physical examination, 12-lead electrocardiogram, and vital sign measurements performed at the Screening and prior to the first dose of study drug. 9. The participant must meet the birth control requirements.
Exclusion criteria
1. The participant has a history of clinically significant endocrine, gastrointestinal (including motility disorder and intestinal obstruction), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary, or presents with major neurological (including stroke and chronic seizures) abnormalities or diseases. 2. The participant has participated in another investigational trial within 4 weeks before the pretrial visit (Screening). The 4-week window will be derived from the date of the last trial procedure and/or adverse event (AE) related to the trial procedure in the previous trial to the Screening Visit of the current trial. 3. The participant is an employee or immediate family member (e.g., spouse, parent, child, sibling) of the sponsor. 4. The participant has a history of cancer (malignancy). 5. The participant has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food. 6. The participant has a positive alcohol or drug or immunological screen. 7. The participant is of childbearing potential or lactating. 8. The participant had major surgery, received or lost 1 unit of blood (approximately 500 milliliters \[mL\]) within 8 weeks prior to the first dose of study drug. 9. The participant with any gastrointestinal (GI) surgery that could impact upon the absorption of study drug. 10. The participant has a known hypersensitivity to any component of the formulation of TAK-831 or related compounds. 11. The participant is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies, beginning approximately 7 days before administration of the initial dose of trial drug, throughout the trial (including washout intervals between trial periods), until the Follow-up Visit. 12. The participant has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\] per day). 13. The participant who consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. 14. The participant has a history of drug abuse. 15. The participant has a (QT interval with Fridericia's correction method) QTcF \>450 milliseconds (msec) (males) or \>470 msec (females) or PR outside the range of 120 to 220 msec at the Screening Visit or Check-in.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31 |
| Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31 |
| Number of Participants Reporting at Least One TEAE Related to Vital Sign | Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31 |
| Number of Participants Reporting at Least One TEAE Related to Body Weight | Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31 |
| Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31 |
Secondary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-831 | Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose |
| Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 1: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose and Day 17: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose |
| Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831 | Day 17 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post-dose |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Cohort 1: Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72 hours post-dose; Day 17 pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post-dose |
| AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at single site in Japan from 09 October 2018 to 19 June 2019.
Pre-assignment details
Healthy adult participants were randomized to receive TAK-831: under 3-sequential dose escalation design to the sequence of administration of A (100 mg +300 mg), B (100 mg + Placebo), and C (Placebo + 300 mg) in Cohort 1 (Japanese); single dose followed by multiple dose of TAK-831 or Placebo in Cohorts 2, 4, 5 (Japanese) and in Cohort 3 (Chinese).
Participants by arm
| Arm | Count |
|---|---|
| Japanese Cohort 1-A: TAK-831 100 mg + TAK-831 300 mg TAK-831 100 mg, tablet, orally, once on Day 1 of Part 1, followed by TAK-831 300 mg, tablet, orally, once on Day 1 (Day 9) of Part 2 in healthy Japanese participants. | 4 |
| Japanese Cohort 1-B: TAK-831 100 mg + Placebo TAK-831 100 mg, tablet, orally, once on Day 1 of Part 1 followed by TAK-831 matching placebo, tablet, orally, once on Day 1 (Day 9) of Part 2 in healthy Japanese participants. | 2 |
| Japanese Cohort 1-C: Placebo + TAK-831 300 mg TAK-831 matching placebo, tablet, orally, once on Day 1 of Part 1 followed by TAK-831 300 mg, tablet, orally, once on Day 1 (Day 9) of Part 2 in healthy Japanese participants. | 2 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo TAK-831 matching placebo, tablet, orally, once on Day 1 and once daily from Day 4 to Day 17 in healthy Japanese participants. | 6 |
| Japanese Cohort 2: TAK-831 300 mg TAK-831 300 mg, tablet, orally, once on Day 1 and once daily from Day 4 to Day 17 in healthy Japanese participants. | 6 |
| Japanese Cohort 4: TAK-831 600 mg TAK-831 600 mg, tablet, orally, once on Day 1 and once daily from Day 4 to Day 17 in healthy Japanese participants. | 6 |
| Japanese Cohort 5: TAK-831 50 mg TAK-831 50 mg, tablet, orally, once on Day 1 and once daily from Day 4 to Day 17 in healthy Japanese participants. | 6 |
| Chinese Cohort 3: Placebo TAK-831 matching placebo, tablet, orally, once on Day 1 and once daily from Day 4 to Day 17 in healthy Chinese participants. | 2 |
| Chinese Cohort 3: TAK-831 600 mg TAK-831 600 mg, tablet, orally, once on Day 1 and once daily from Day 4 to Day 17 in healthy Chinese participants. | 6 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Japanese Cohort 1-B: TAK-831 100 mg + Placebo | Japanese Cohort 1-C: Placebo + TAK-831 300 mg | Japanese Cohort 1-A: TAK-831 100 mg + TAK-831 300 mg | Japanese Cohort 2, 4 and 5: Pooled Placebo | Japanese Cohort 2: TAK-831 300 mg | Japanese Cohort 4: TAK-831 600 mg | Japanese Cohort 5: TAK-831 50 mg | Chinese Cohort 3: Placebo | Chinese Cohort 3: TAK-831 600 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 40 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 40 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 2 Participants | 2 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 |
| other Total, other adverse events | 0 / 4 | 2 / 6 | 0 / 6 | 4 / 6 | 4 / 6 | 1 / 6 | 2 / 6 | 1 / 2 | 2 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 |
Outcome results
Primary
Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters
Time frame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Cohort 1: Placebo | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Japanese Cohort 1: TAK-831 100 mg | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Japanese Cohort 1: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Japanese Cohort 2: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Japanese Cohort 4: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Japanese Cohort 5: TAK-831 50 mg | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Chinese Cohort 3: Placebo | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
| Chinese Cohort 3: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to 12-lead Electrocardiogram (ECG) Parameters | 0 Participants |
Primary
Number of Participants Reporting at Least One TEAE Related to Body Weight
Time frame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Cohort 1: Placebo | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Japanese Cohort 1: TAK-831 100 mg | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Japanese Cohort 1: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Japanese Cohort 2: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Japanese Cohort 4: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Japanese Cohort 5: TAK-831 50 mg | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Chinese Cohort 3: Placebo | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
| Chinese Cohort 3: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to Body Weight | 0 Participants |
Primary
Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results
Time frame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Cohort 1: Placebo | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 0 Participants |
| Japanese Cohort 1: TAK-831 100 mg | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 2 Participants |
| Japanese Cohort 1: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 0 Participants |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 2 Participants |
| Japanese Cohort 2: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 2 Participants |
| Japanese Cohort 4: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 1 Participants |
| Japanese Cohort 5: TAK-831 50 mg | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 1 Participants |
| Chinese Cohort 3: Placebo | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 1 Participants |
| Chinese Cohort 3: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to Laboratory Test Results | 0 Participants |
Primary
Number of Participants Reporting at Least One TEAE Related to Vital Sign
Time frame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Cohort 1: Placebo | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
| Japanese Cohort 1: TAK-831 100 mg | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
| Japanese Cohort 1: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 1 Participants |
| Japanese Cohort 2: TAK-831 300 mg | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 1 Participants |
| Japanese Cohort 4: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
| Japanese Cohort 5: TAK-831 50 mg | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
| Chinese Cohort 3: Placebo | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
| Chinese Cohort 3: TAK-831 600 mg | Number of Participants Reporting at Least One TEAE Related to Vital Sign | 0 Participants |
Primary
Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: Cohort 1: Baseline up to Day 23; Cohorts 2-5: Baseline up to Day 31
Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Japanese Cohort 1: Placebo | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 0 Participants |
| Japanese Cohort 1: TAK-831 100 mg | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 2 Participants |
| Japanese Cohort 1: TAK-831 300 mg | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 0 Participants |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 4 Participants |
| Japanese Cohort 2: TAK-831 300 mg | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 4 Participants |
| Japanese Cohort 4: TAK-831 600 mg | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| Japanese Cohort 5: TAK-831 50 mg | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 2 Participants |
| Chinese Cohort 3: Placebo | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| Chinese Cohort 3: TAK-831 600 mg | Number of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE) | 2 Participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
Time frame: Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose
Population: The PK analysis set included participants who received at least one dose of study drug, and who were appropriately evaluable for at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Cohort 1: Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 1581 h*ng/mL | Geometric Coefficient of Variation 11.7 |
| Japanese Cohort 1: TAK-831 100 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 3653 h*ng/mL | Geometric Coefficient of Variation 12.2 |
| Japanese Cohort 1: TAK-831 300 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 3730 h*ng/mL | Geometric Coefficient of Variation 31.9 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 6518 h*ng/mL | Geometric Coefficient of Variation 26.2 |
| Japanese Cohort 2: TAK-831 300 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 923.6 h*ng/mL | Geometric Coefficient of Variation 22.1 |
| Japanese Cohort 4: TAK-831 600 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | 5530 h*ng/mL | Geometric Coefficient of Variation 22.3 |
Secondary
AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831
Time frame: Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose
Population: The PK analysis set included participants who received at least one dose of study drug, and who were appropriately evaluable for at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Cohort 1: Placebo | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | 1553 hour*nanogram per milliliter(h*ng/mL) | Geometric Coefficient of Variation 11.8 |
| Japanese Cohort 1: TAK-831 100 mg | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | 3630 hour*nanogram per milliliter(h*ng/mL) | Geometric Coefficient of Variation 11.9 |
| Japanese Cohort 1: TAK-831 300 mg | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | 3700 hour*nanogram per milliliter(h*ng/mL) | Geometric Coefficient of Variation 32.2 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | 6477 hour*nanogram per milliliter(h*ng/mL) | Geometric Coefficient of Variation 26.2 |
| Japanese Cohort 2: TAK-831 300 mg | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | 847.4 hour*nanogram per milliliter(h*ng/mL) | Geometric Coefficient of Variation 21.5 |
| Japanese Cohort 4: TAK-831 600 mg | AUClast: Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration for TAK-831 | 5504 hour*nanogram per milliliter(h*ng/mL) | Geometric Coefficient of Variation 22.3 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-831
Time frame: Cohort 1: Day 1 pre-dose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose
Population: The pharmacokinetic (PK) analysis set included participants who received at least one dose of study drug, and who were appropriately evaluable for at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Cohort 1: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 985.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 20.8 |
| Japanese Cohort 1: TAK-831 100 mg | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1823 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53.7 |
| Japanese Cohort 1: TAK-831 300 mg | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 981.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29.1 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1602 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42.1 |
| Japanese Cohort 2: TAK-831 300 mg | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 339.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33.3 |
| Japanese Cohort 4: TAK-831 600 mg | Cmax: Maximum Observed Plasma Concentration for TAK-831 | 1807 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28.5 |
Secondary
Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831
Time frame: Day 1: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 and 72 hours post-dose and Day 17: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose
Population: The PK analysis set included participants who received at least one dose of study drug, and who were appropriately evaluable for at least 1 PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Japanese Cohort 1: Placebo | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 1 | 3576 h*ng/mL | Geometric Coefficient of Variation 30.6 |
| Japanese Cohort 1: Placebo | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 17 | 2738 h*ng/mL | Geometric Coefficient of Variation 31.1 |
| Japanese Cohort 1: TAK-831 100 mg | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 17 | 8237 h*ng/mL | Geometric Coefficient of Variation 28.4 |
| Japanese Cohort 1: TAK-831 100 mg | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 1 | 6211 h*ng/mL | Geometric Coefficient of Variation 26.8 |
| Japanese Cohort 1: TAK-831 300 mg | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 1 | 794.5 h*ng/mL | Geometric Coefficient of Variation 22.2 |
| Japanese Cohort 1: TAK-831 300 mg | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 17 | 983.0 h*ng/mL | Geometric Coefficient of Variation 22.3 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 1 | 5340 h*ng/mL | Geometric Coefficient of Variation 22.3 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Cohorts 2 to 5, AUCtau: Area Under the Plasma Concentration-time Curve From Time 0 to [Time] Over the Dosing Interval for TAK-831 | Day 17 | 5839 h*ng/mL | Geometric Coefficient of Variation 21.6 |
Secondary
Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831
Time frame: Day 17 pre-dose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12 and 24 hours post-dose
Population: The PK analysis set included participants who received at least one dose of study drug, and who were appropriately evaluable for at least 1 PK parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Japanese Cohort 1: Placebo | Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831 | 831.8 ng/mL | Geometric Coefficient of Variation 29.1 |
| Japanese Cohort 1: TAK-831 100 mg | Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831 | 1903 ng/mL | Geometric Coefficient of Variation 33.6 |
| Japanese Cohort 1: TAK-831 300 mg | Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831 | 417.0 ng/mL | Geometric Coefficient of Variation 23.8 |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Cohorts 2 to 5, Cmax, ss: Maximum Observed Steady-state Plasma Concentration During a Dosing Interval for TAK-831 | 1581 ng/mL | Geometric Coefficient of Variation 42.4 |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831
Time frame: Cohort 1: Day 1 pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72 hours post-dose; Cohorts 2 to 5: Day 1 pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72 hours post-dose; Day 17 pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24 hours post-dose
Population: The PK analysis set included participants who received at least one dose of study drug, and who were appropriately evaluable for at least 1 PK parameter.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Japanese Cohort 1: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.5000 hour |
| Japanese Cohort 1: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 17 | NA hour |
| Japanese Cohort 1: TAK-831 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.5000 hour |
| Japanese Cohort 1: TAK-831 100 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 17 | NA hour |
| Japanese Cohort 1: TAK-831 300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 2.000 hour |
| Japanese Cohort 1: TAK-831 300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 17 | 1.750 hour |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 1.750 hour |
| Japanese Cohort 2, 4 and 5: Pooled Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 17 | 2.000 hour |
| Japanese Cohort 2: TAK-831 300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 0.5000 hour |
| Japanese Cohort 2: TAK-831 300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 17 | 0.5000 hour |
| Japanese Cohort 4: TAK-831 600 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 1 | 1.500 hour |
| Japanese Cohort 4: TAK-831 600 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-831 | Day 17 | 2.000 hour |