Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to characterize safety and tolerability of TAK-418 in non-Japanese and Japanese healthy female participants when administered at single or multiple (once daily \[QD\]) oral doses.
Detailed description
The drug being tested in this study is called TAK-418. This study will assess the safety, tolerability, PK and PD of single and multiple rising doses of TAK-418 in healthy Japanese or non-Japanese females. The study will enroll approximately 48 participants in 6 cohorts and each cohort will have 8 participants. The study will include 2 parts: single rising dose (SRD) in Cohort 1 and multiple rising dose (MRD) in Cohorts 2 to 6. Cohort 3 will include cerebrospinal fluid (CSF) collection. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 6 cohorts. This two-center trial will be conducted in the United States. The overall time to participate in Cohort 1 of this study is approximately 105 days and 98 days in Cohort 2. Participants will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-418
TAK-418 capsules.
DRUGTAK-418 Matching Placebo
TAK-418 matching placebo capsules.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Has a body mass index (BMI) greater than or equal to (\>=) 18.5 and less than or equal to (\<=) 30.0 kilogram per square meter (kg/m\^2) at the Screening Visit. (Cohorts 1 to 4 only). 2. Is a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the first dose of trial drug or invasive procedure. 3. The participant either is of nonchildbearing potential, OR, if of childbearing potential, is using a highly effective method of contraception with low user dependency during the entire duration of the study. For Cohorts 5 and 6 (Japanese participants) only: 1\. Has a BMI \>=18.0 and \<= 26.0 kg/m\^2, at the Screening Visit.
Exclusion criteria
1. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) antibody/antigen, at Screening. 2. Had major surgery, donated or lost 1 unit of blood (approximately 500 milliliter \[mL\]) within 4 weeks before the Screening Visit. 3. 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). 4. 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. 5. Has a substance abuse disorder. 6. Has risk of suicide according to the investigator's clinical judgment per Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or has made a suicide attempt in the 6 months before Screening. 7. Has luteinizing hormone (LH), follicle-stimulating hormone (FSH), or estradiol levels that are clinically abnormal. 8. Has a resting heart rate outside of the range of 50 to 100 beats per minute, confirmed on repeat testing within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1). For Cohort 3 only (includes CSF sample collection): 1. Has had CSF collection performed within 30 days before Check-in (Day -1). 2. Has significant vertebral deformities (scoliosis or kyphosis) that, in the opinion of the investigator, may interfere with the lumbar puncture procedure. 3. Has a local infection at the puncture site. 4. Has thrombocytopenia or other suspected bleeding tendencies noted before the procedure. 5. Has developed signs and symptoms of spinal radiculopathy, including lower extremity pain and paresthesia. 6. Has any focal neurological deficit that might suggest an increase in intracranial pressure. 7. Has any abnormal finding on ophthalmological assessment/fundoscopy indicative of raised intracranial pressure (that is, optic disc swelling/edema; or \[uncontrolled\] hypertensive retinopathy). 8. Regularly has moderate-to-severe headaches requiring analgesics. 9. Has any bleeding abnormality or history of bleeding abnormalities. 10. Has abnormal coagulation tests (prothrombin time \[PT\]/international normalized ratio \[INR\], partial thromboplastin time \[PTT\]) at Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | Baseline up to Day 70 |
| Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | Baseline up to Day 70 |
| Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Baseline up to Day 60 |
| Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Baseline up to Day 70 |
| Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | Baseline up to Day 60 |
| Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | Baseline up to Day 60 |
| Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | Baseline up to Day 70 |
| Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | Baseline up to Day 60 |
Secondary
| Measure | Time frame |
|---|---|
| Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Days 1 and 10 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-418 | Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Tmax: Time to Reach the Cmax for TAK-418 | Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1 | Day 1 pre-dose and at multiple time points (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 30 May 2018 to 26 December 2018.
Pre-assignment details
Healthy female participants were enrolled to receive TAK-418 as single rising dose (SRD) dose of 120 milligram (mg), or 160 mg (non-Japanese cohort), and/or placebo in a crossover fashion; and multiple rising dose (MRD) of 20 mg, 60 mg, 160 mg (non-Japanese cohort) or 20 mg (Japanese cohort). The study was terminated early due to business decision.
Participants by arm
| Arm | Count |
|---|---|
| Non-Japanese Cohort 1: TAK-418 120 mg + Placebo TAK-418 120 mg capsule, orally, once on Day 1 of Period A, followed by a washout period of at least 14 days, further followed by TAK-418 120 mg placebo-matching capsule, orally, once on Day 1 of Period B. | 2 |
| Non-Japanese Cohort 1: TAK-418 120 mg + TAK-418 160 mg TAK-418 120 mg capsule, orally, once on Day 1 of Period A, followed by a washout period of at least 14 days, further followed by TAK-418 160 mg capsule, orally, once on Day 1 of Period B. | 4 |
| Non-Japanese Cohort 1: Placebo + TAK-418 160 mg TAK-418 160 mg placebo-matching capsule, orally, once on Day 1 of Period A, followed by a washout period of at least 14 days, further followed by TAK-418 160 mg capsule, orally, once on Day 1 of Period B. | 2 |
| Non-Japanese Cohorts 2 to 4: Pooled Placebo TAK-418 placebo-matching capsule, orally, once daily for 10 days. | 5 |
| Japanese Cohort 5: Placebo TAK-418 placebo-matching capsule, orally, once daily for 10 days. | 1 |
| Non-Japanese Cohort 2: TAK-418 20 mg TAK-418 20 mg, capsule, orally, once daily for 10 days. | 6 |
| Non-Japanese Cohort 3: TAK-418 60 mg TAK-418 60 mg, capsule, orally, once daily for 10 days. | 6 |
| Non-Japanese Cohort 4: TAK-418 160 mg TAK-418 160 mg, capsule, orally, once daily for 10 days. | 3 |
| Japanese Cohort 5: TAK-418 20 mg TAK-418 20 mg, capsule, orally, once daily for 10 days. | 3 |
| Total | 32 |
Baseline characteristics
| Characteristic | Total | Non-Japanese Cohort 4: TAK-418 160 mg | Non-Japanese Cohort 3: TAK-418 60 mg | Non-Japanese Cohort 2: TAK-418 20 mg | Japanese Cohort 5: Placebo | Non-Japanese Cohorts 2 to 4: Pooled Placebo | Non-Japanese Cohort 1: Placebo + TAK-418 160 mg | Non-Japanese Cohort 1: TAK-418 120 mg + TAK-418 160 mg | Non-Japanese Cohort 1: TAK-418 120 mg + Placebo | Japanese Cohort 5: TAK-418 20 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 43.4 years STANDARD_DEVIATION 10.6 | 43.3 years STANDARD_DEVIATION 4.04 | 46.7 years STANDARD_DEVIATION 10.93 | 39.2 years STANDARD_DEVIATION 12.32 | 49.0 years | 47.8 years STANDARD_DEVIATION 11.78 | 39.0 years STANDARD_DEVIATION 18.38 | 39.8 years STANDARD_DEVIATION 11.32 | 33.5 years STANDARD_DEVIATION 7.78 | 50.3 years STANDARD_DEVIATION 3.51 |
| Body Mass Index (BMI) | 25.16 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.775 | 26.47 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.202 | 26.42 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.872 | 24.53 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.401 | 24.30 kilogram per square meter (kg/m^2) | 26.62 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.599 | 23.75 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.182 | 26.23 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.636 | 23.90 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.808 | 20.77 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.553 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 2 Participants | 5 Participants | 6 Participants | 1 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants |
| Ethnicity (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 |
| Height | 164.09 centimeter (cm) STANDARD_DEVIATION 7.485 | 172.3 centimeter (cm) STANDARD_DEVIATION 7.23 | 163.0 centimeter (cm) STANDARD_DEVIATION 8.15 | 164.7 centimeter (cm) STANDARD_DEVIATION 6.47 | 167.0 centimeter (cm) | 162.8 centimeter (cm) STANDARD_DEVIATION 7.85 | 166.50 centimeter (cm) STANDARD_DEVIATION 6.364 | 161.00 centimeter (cm) STANDARD_DEVIATION 4.243 | 173.00 centimeter (cm) STANDARD_DEVIATION 5.657 | 154.7 centimeter (cm) STANDARD_DEVIATION 2.52 |
| 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 | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 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 | 22 Participants | 3 Participants | 5 Participants | 6 Participants | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 32 Participants | 3 Participants | 6 Participants | 6 Participants | 1 Participants | 5 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 32 Participants | 3 Participants | 6 Participants | 6 Participants | 1 Participants | 5 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 67.859 kilogram (kg) STANDARD_DEVIATION 9.4141 | 78.27 kilogram (kg) STANDARD_DEVIATION 5.848 | 70.22 kilogram (kg) STANDARD_DEVIATION 9.1 | 66.60 kilogram (kg) STANDARD_DEVIATION 6.69 | 67.90 kilogram (kg) | 70.60 kilogram (kg) STANDARD_DEVIATION 7.09 | 66.250 kilogram (kg) STANDARD_DEVIATION 13.7886 | 67.875 kilogram (kg) STANDARD_DEVIATION 5.5506 | 71.050 kilogram (kg) STANDARD_DEVIATION 9.8288 | 49.60 kilogram (kg) STANDARD_DEVIATION 3.857 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 1 / 2 | 0 / 2 | 3 / 6 | 2 / 6 | 3 / 5 | 1 / 1 | 5 / 6 | 6 / 6 | 3 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE)
Time frame: Baseline up to Day 60
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | TEAE | 1 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | SAE | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | SAE | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | TEAE | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | TEAE | 3 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | SAE | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | TEAE | 2 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAE) | SAE | 0 Participants |
Primary
Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
Time frame: Baseline up to Day 60
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG Mean Heart Rate <50 bpm | 0 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval >=460 millisecond (msec) | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval >=460 millisecond (msec) | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG Mean Heart Rate <50 bpm | 1 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG Mean Heart Rate <50 bpm | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval >=460 millisecond (msec) | 1 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | ECG Mean Heart Rate <50 bpm | 1 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose | QT Interval >=460 millisecond (msec) | 0 Participants |
Primary
Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose
Time frame: Baseline up to Day 60
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 1 Participants |
Primary
Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose
Time frame: Baseline up to Day 60
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate less than (<) 50 beats per minute (bpm) | 0 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Temperature <35.6 Celsius (C) | 0 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate less than (<) 50 beats per minute (bpm) | 1 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Temperature <35.6 Celsius (C) | 1 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate less than (<) 50 beats per minute (bpm) | 1 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Temperature <35.6 Celsius (C) | 1 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate less than (<) 50 beats per minute (bpm) | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Temperature <35.6 Celsius (C) | 1 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 1: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 1 Participants |
Primary
Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE
Time frame: Baseline up to Day 70
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | TEAE | 3 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | SAE | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | TEAE | 1 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | SAE | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | TEAE | 5 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | SAE | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | TEAE | 6 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | SAE | 0 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | TEAE | 3 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | SAE | 0 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | TEAE | 1 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants Who Experienced at Least One TEAEs and SAE | SAE | 0 Participants |
Primary
Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose
Time frame: Baseline up to Day 70
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | 1 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | 0 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | 0 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants Who Meet the Markedly Abnormal Values of 12-lead ECG Parameters at Least Once Post Dose | 0 Participants |
Primary
Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose
Time frame: Baseline up to Day 70
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Clinical Laboratory Values at Least Once Postdose | 0 Participants |
Primary
Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose
Time frame: Baseline up to Day 70
Population: The safety set included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate greater than (>) 120 bpm | 1 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| Non-Japanese Cohort 1; Period A: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate greater than (>) 120 bpm | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| Non-Japanese Cohort 1; Period B: Placebo | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate greater than (>) 120 bpm | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate greater than (>) 120 bpm | 0 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Diastolic Blood Pressure <50 mmHg | 2 Participants |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate greater than (>) 120 bpm | 0 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 0 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Diastolic Blood Pressure <50 mmHg | 0 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Systolic Blood Pressure <85 mmHg | 1 Participants |
| Japanese Cohort 5: TAK-418 20 mg | Cohorts 2 to 5: Number of Participants With Markedly Abnormal Criteria for Vital Signs at Least Once Postdose | Pulse Rate greater than (>) 120 bpm | 0 Participants |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-418
Time frame: Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK set included all participants from the safety set who had at least 1 measurable post dose plasma or CSF concentration or amount of drug in urine of TAK-418F. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 1 | 714.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21.6 |
| Non-Japanese Cohort 1; Period B: Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 1 | 750.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.3 |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 10 | 113.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30.8 |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 1 | 81.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35.8 |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 10 | 303.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17.6 |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 1 | 270.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21.6 |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 1 | 657.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| Non-Japanese Cohort 4: TAK-418 160 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 10 | 692.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15.4 |
| Japanese Cohort 5: TAK-418 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 10 | 171.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 5.9 |
| Japanese Cohort 5: TAK-418 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-418 | Day 1 | 154.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 5.9 |
Secondary
Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The pharmacokinetic (PK) set included all participants from the safety set who had at least 1 measurable post dose plasma or cerebrospinal fluid (CSF) concentration or amount of drug in urine of TAK-418F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1 | 3761.2 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 20.8 |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 1; AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-418 on Day 1 | 4229.0 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 40.4 |
Secondary
Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10
Time frame: Days 1 and 10 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK set included all participants from the safety set who had at least 1 measurable post dose plasma or CSF concentration or amount of drug in urine of TAK-418F.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 1 | 503.3 hr*ng/mL | Standard Deviation 165.71 |
| Non-Japanese Cohort 1; Period A: Placebo | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 10 | 668.2 hr*ng/mL | Standard Deviation 228.83 |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 10 | 1660.5 hr*ng/mL | Standard Deviation 421.77 |
| Non-Japanese Cohort 1; Period B: Placebo | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 1 | 1445.5 hr*ng/mL | Standard Deviation 353.26 |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 1 | 3747.3 hr*ng/mL | Standard Deviation 239.53 |
| Non-Japanese Cohort 1: TAK 418 120 mg | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 10 | 4058.3 hr*ng/mL | Standard Deviation 249.49 |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 1 | 610.3 hr*ng/mL | Standard Deviation 87.89 |
| Non-Japanese Cohort 1: TAK 418 160 mg | Cohort 2 to 5: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Over the Dosing Interval for TAK-418 on Days 1 and 10 | Day 10 | 677.3 hr*ng/mL | Standard Deviation 73.66 |
Secondary
Tmax: Time to Reach the Cmax for TAK-418
Time frame: Cohort 1: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cohorts 2 to 5: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK set included all participants from the safety set who had at least 1 measurable post dose plasma or CSF concentration or amount of drug in urine of TAK-418F. PK-evaluable population where data at specified time points was available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Non-Japanese Cohort 1; Period A: Placebo | Tmax: Time to Reach the Cmax for TAK-418 | Day 1 | 1.500 hour |
| Non-Japanese Cohort 1; Period B: Placebo | Tmax: Time to Reach the Cmax for TAK-418 | Day 1 | 1.250 hour |
| Non-Japanese Cohort 1: TAK 418 120 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 10 | 1.260 hour |
| Non-Japanese Cohort 1: TAK 418 120 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 1 | 1.750 hour |
| Non-Japanese Cohort 1: TAK 418 160 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 10 | 1.250 hour |
| Non-Japanese Cohort 1: TAK 418 160 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 1 | 1.500 hour |
| Non-Japanese Cohort 4: TAK-418 160 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 1 | 1.500 hour |
| Non-Japanese Cohort 4: TAK-418 160 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 10 | 1.000 hour |
| Japanese Cohort 5: TAK-418 20 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 10 | 1.000 hour |
| Japanese Cohort 5: TAK-418 20 mg | Tmax: Time to Reach the Cmax for TAK-418 | Day 1 | 1.000 hour |