Healthy Participants
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the safety and tolerability of TAK-418 following single oral doses in healthy participants.
Detailed description
The drug being tested in this study is called TAK-418. TAK-418 is being tested in healthy participants in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of single oral doses. The study will enroll approximately 40 healthy participants. The study consists of equally divided 5 sequential cohorts of 8 participants each. In each of the following cohorts, 6 participants will be randomized to receive TAK-418 and 2 participants will receive matching placebo-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need): * Cohort 1: TAK-418 5 mg * Cohort 2: TAK-418 15 mg * Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed * Cohort 4: TAK-418 40 mg * Cohort 5: TAK-418 60 mg All participants will be asked to take TAK-418 or placebo-matching capsule once on Day 1 in each cohort. A washout period of 28-days will be maintained between the doses in Cohort 3. This single center trial will be conducted in the United States. Participants in this study will be assigned to one of 5 possible dose cohorts. Male participants will return for additional outpatient visits on Days 91 and 93 (+/- 7 days) and may return for outpatient visits on Days 182 and 184 (+/- 7 days) (depending on results from the Day 93 Visit).
Interventions
DRUGTAK-418
TAK-418 Capsule.
DRUGTAK-418 Placebo
TAK-418 placebo-matching capsules.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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 male or female participants with a body mass index (BMI) within the range of 18.5 -30.0 kilogram per square meter (kg/m\^2) at the Screening Visit. 2. Is a nonsmoker who has not used tobacco or nicotine-containing products (example, nicotine patch) for at least 6 months before trial drug administration of the initial dose of trial drug or invasive procedure. 3. Must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead ECG, and vital sign measurements performed at the Screening Visit and before administration of the initial dose of trial drug or invasive procedure as per principal investigator's judgment. 4. Female subjects with no childbearing potential, defined by at least 1 of the following criteria: * Postmenopausal (defined as 12 months of spontaneous amenorrhea in women aged greater than \[\>\]45 years, 6 months of spontaneous amenorrhea in women aged \>45 years with serum follicle-stimulating hormone \[FSH\] levels \>40 milli-international units per milliliter \[mIU/mL\]). Appropriate documentation of FSH levels is required. * Surgically sterile by hysterectomy and/or bilateral oophorectomy with appropriate documentation of surgical procedure. * Had a tubal ligation with appropriate documentation of surgical procedure. * Has a congenital condition resulting in no uterus.
Exclusion criteria
1. Has had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter \[mL\]) within 4 weeks before the Screening Visit. 2. Has a risk of suicide according to the investigator's clinical judgment per the Columbia-Suicide Severity Rating Scale at Screening or has made a suicide attempt in the 6 months before Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline Up to Day 184 |
| Number of Participants Who Discontinued Due to an Adverse Event (AE) | Baseline Up to Day 184 |
| Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | Baseline Up to Day 184 |
| Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | Baseline Up to Day 184 |
| Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Baseline Up to day 184 |
| Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | Baseline Up to Day 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose | — |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose | — |
| Cmax: Maximum Observed Plasma Concentration for TAK-418F | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose | The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at single site in the United States from 21 July 2017 to 12 May 2018.
Pre-assignment details
Healthy participants were randomized to receive TAK-418 or matching placebo in Cohorts 1 to 5.
Participants by arm
| Arm | Count |
|---|---|
| Cohorts 1-5: Placebo TAK-418 placebo-matching, capsule, orally, once on Day 1. | 10 |
| Cohort 1: TAK-418 5 mg TAK-418 5 mg, capsule, orally, once on Day 1. | 6 |
| Cohort 2: TAK-418 15 mg TAK-418 15 mg, capsule, orally, once on Day 1. | 6 |
| Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed TAK-418 30 mg, capsule, in fasted state, orally, once on Day 1, followed by a 28-day washout period, further followed by TAK-418 30 mg, capsule, in fed state, orally, once on Day 1. | 6 |
| Cohort 4: TAK-418 40 mg TAK-418 40 mg, capsule, orally, once on Day 1. | 6 |
| Cohort 5: TAK-418 60 mg TAK-418 60 mg, capsule, orally, once on Day 1. | 6 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Positive alcohol test | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2: TAK-418 15 mg | Cohort 3: TAK-418 30 mg Fasted + TAK-418 30 mg Fed | Cohorts 1-5: Placebo | Total | Cohort 4: TAK-418 40 mg | Cohort 1: TAK-418 5 mg | Cohort 5: TAK-418 60 mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 10.8 | 40.0 years STANDARD_DEVIATION 10.6 | 36.4 years STANDARD_DEVIATION 9.63 | 36.5 years STANDARD_DEVIATION 9.43 | 33.2 years STANDARD_DEVIATION 6.49 | 37.2 years STANDARD_DEVIATION 10.42 | 38.7 years STANDARD_DEVIATION 10.03 |
| Body mass index (BMI) | 26.83 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.835 | 27.83 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.414 | 26.94 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.065 | 26.32 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.864 | 24.32 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.988 | 25.82 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.44 | 25.73 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.992 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 7 Participants | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 9 Participants | 33 Participants | 5 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 174.8 centimeter (cm) STANDARD_DEVIATION 3.19 | 172.5 centimeter (cm) STANDARD_DEVIATION 5.09 | 173.4 centimeter (cm) STANDARD_DEVIATION 8.66 | 174.0 centimeter (cm) STANDARD_DEVIATION 7.89 | 181.2 centimeter (cm) STANDARD_DEVIATION 5.08 | 171.0 centimeter (cm) STANDARD_DEVIATION 8.1 | 171.5 centimeter (cm) STANDARD_DEVIATION 11.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants | 6 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 5 Participants | 9 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 4 Participants | 4 Participants | 22 Participants | 2 Participants | 4 Participants | 5 Participants |
| Region of Enrollment United States | 6 Participants | 6 Participants | 10 Participants | 40 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 2 Participants | 8 Participants | 0 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 8 Participants | 32 Participants | 6 Participants | 4 Participants | 3 Participants |
| Weight | 81.8 kilogram (kg) STANDARD_DEVIATION 6.83 | 82.5 kilogram (kg) STANDARD_DEVIATION 4.22 | 81.2 kilogram (kg) STANDARD_DEVIATION 12.34 | 79.8 kilogram (kg) STANDARD_DEVIATION 11 | 80.0 kilogram (kg) STANDARD_DEVIATION 12.43 | 76.0 kilogram (kg) STANDARD_DEVIATION 13.58 | 76.1 kilogram (kg) STANDARD_DEVIATION 15.23 |
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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 10 | 2 / 6 | 2 / 6 | 3 / 6 | 1 / 5 | 3 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline Up to Day 184
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 4 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 2 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 2 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 participants |
Primary
Number of Participants Who Discontinued Due to an Adverse Event (AE)
Time frame: Baseline Up to Day 184
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Discontinued Due to an Adverse Event (AE) | 0 participants |
Primary
Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose
Time frame: Baseline Up to Day 184
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Neurological Assessment Measurements at Least Once Post Dose | 0 participants |
Primary
Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
Time frame: Baseline Up to Day 14
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 0 participants |
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 1 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 2 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 1 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 1 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT interval (Milliseconds) | 1 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG ventricular rate(Beats/ minute) | 0 participants |
Primary
Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
Time frame: Baseline Up to Day 184
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose | 0 participants |
Primary
Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
Time frame: Baseline Up to day 184
Population: The safety analysis set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 0 participants |
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 0 participants |
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 0 participants |
| Cohorts 1-5: Placebo | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 0 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 0 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 0 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 1 participants |
| Cohort 1: TAK-418 5 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 0 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 0 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 1 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 1 participants |
| Cohort 2: TAK-418 15 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 0 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 1 participants |
| Cohort 3A: TAK-418 30 mg Fasted | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 0 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 1 participants |
| Cohort 3B: TAK-418 30 mg Fed | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 1 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 0 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 1 participants |
| Cohort 4: TAK-418 40 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature < 35.6 degrees celsius (°C) | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Diastolic blood pressure less than (<) 50 mmHg | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Systolic blood pressure < 85 mmHg | 0 participants |
| Cohort 5: TAK-418 60 mg | Number of Participants Who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose | Temperature greater than (>) 37.7 (°C) | 2 participants |
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-5: Placebo | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | 84.9 h*ng/mL | Geometric Coefficient of Variation 47.4 |
| Cohort 1: TAK-418 5 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | 296.3 h*ng/mL | Geometric Coefficient of Variation 22.1 |
| Cohort 2: TAK-418 15 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | 659.6 h*ng/mL | Geometric Coefficient of Variation 8 |
| Cohort 3A: TAK-418 30 mg Fasted | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | 626.0 h*ng/mL | Geometric Coefficient of Variation 22.7 |
| Cohort 3B: TAK-418 30 mg Fed | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | 681.0 h*ng/mL | Geometric Coefficient of Variation 26.9 |
| Cohort 4: TAK-418 40 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418F | 1519.9 h*ng/mL | Geometric Coefficient of Variation 33.3 |
90% CI: [0.825, 1.097]
90% CI: [1, 1.22]
Secondary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base)
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-5: Placebo | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | 77.3 hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 47.1 |
| Cohort 1: TAK-418 5 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | 290.4 hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.8 |
| Cohort 2: TAK-418 15 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | 649.4 hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 8.5 |
| Cohort 3A: TAK-418 30 mg Fasted | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | 616.2 hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.1 |
| Cohort 3B: TAK-418 30 mg Fed | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | 674.1 hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27 |
| Cohort 4: TAK-418 40 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of TAK-418F (TAK-418 Free Base) | 1576.3 hour nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 33.5 |
90% CI: [0.823, 1.099]
90% CI: [1.04, 1.25]
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-418F
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohorts 1-5: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-418F | 21.54 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 35.9 |
| Cohort 1: TAK-418 5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418F | 61.90 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 26.6 |
| Cohort 2: TAK-418 15 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418F | 163.64 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 20.9 |
| Cohort 3A: TAK-418 30 mg Fasted | Cmax: Maximum Observed Plasma Concentration for TAK-418F | 94.93 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 33.8 |
| Cohort 3B: TAK-418 30 mg Fed | Cmax: Maximum Observed Plasma Concentration for TAK-418F | 155.32 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 34.3 |
| Cohort 4: TAK-418 40 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418F | 321.52 nanogram per millilitre (ng/mL) | Geometric Coefficient of Variation 14.1 |
90% CI: [0.431, 0.781]
90% CI: [0.96, 1.17]
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F
The pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least one measurable plasma concentration or amount of drug in urine for TAK-418-F.
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohorts 1-5: Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | 1.000 hour |
| Cohort 1: TAK-418 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | 1.000 hour |
| Cohort 2: TAK-418 15 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | 1.000 hour |
| Cohort 3A: TAK-418 30 mg Fasted | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | 3.000 hour |
| Cohort 3B: TAK-418 30 mg Fed | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | 1.250 hour |
| Cohort 4: TAK-418 40 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-418F | 1.000 hour |