Dose Finding Study
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to characterize the safety and tolerability profile of TAK-137 when administered as a single dose of tablets at escalating dose levels in healthy participants.
Detailed description
The drug being tested in this study is called TAK-137. TAK-137 is being tested to find a safe and well-tolerated dose. This study looked at safety (lab results and side effects) and pharmacokinetic properties (drug absorption, distribution, metabolism, and excretion) in people who took TAK-137. This study was designed as a single ascending 6 Cohort dose study with planned doses of 2, 5, 15, 50, and 100 mg and Cohort 6 dose to be determined if the maximum tolerated dose (MTD) was not reached. Anticipated enrollment was 48. This study enrolled 47 participants and consisted of 6 Cohorts. Participants in Cohorts 1, 2, 3, 5 and 6 were randomized to receive a single dose of TAK-137 or placebo after a 10-hour fast. Participants in Cohort 4 were randomized to receive a single dose of TAK-137 or placebo under fasted conditions, followed by a single dose of TAK-137 or placebo under fed conditions 14 days later. Participants in cohort 4 will receive the same dose in both fasted and fed conditions. The starting dose was 2 mg followed by administrations of 5, 10, 0.5 and 20 mg. This single-center trial was conducted in the United States. For Cohorts 1, 2, 3, 5, and 6 the overall time to participate in this study was up to 42 days. Participants made 4 visits to the clinic including one 5-day period of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment. For Cohort 4 the overall time to participate in this study was up to 56 days. Participants made 7 visits to the clinic including two 5-day periods of confinement to the clinic, and were contacted by telephone 14 days after last dose of study drug for a follow-up assessment.
Interventions
DRUGTAK-137
TAK-137 tablets
DRUGPlacebo
TAK-137 placebo-matching tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is a healthy male or non-pregnant, non-lactating female adult who is 18 to 55 years of age inclusive at the time of informed consent and first study medication dose. 2. Weighs at least 45 kg and has a body mass index (BMI) between 18 and 30.0 kg/m\^2, inclusive at Screening. 3. Is able to comply with the protocol and is willing to sign the informed consent prior to undergoing any study-related procedures.
Exclusion criteria
1. Has a known hypersensitivity to any component of the formulation of TAK-137. 2. Has a medical condition such as mental retardation that can cause cognitive impairment. 3. Has a risk of suicide according to the Investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale \[C-SSRS\] or has made a suicide attempt in the previous 6 months). 4. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. 5. There is any finding in the participant's medical history, physical examination, or safety laboratory tests (including safety electroencephalogram \[EEG\]) giving reasonable suspicion of a disease that would contraindicate taking TAK-137, or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias. 6. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | Day 1 to 14 days after the last dose of study medication(Up to 30 days) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug. |
| Percentage of Participants With Abnormal Safety Laboratory Findings | Day 1 to 14 days after the last dose of study medication (Up to 30 Days) | The percentage of participants with any markedly abnormal standard safety laboratory values was collected throughout study. |
| Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Day 1 to 14 days after the last dose of study medication | The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | Day 1 | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. |
| Terminal Elimination Half-life (T1/2) for TAK-137_101 | Day 1 | Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. |
| Apparent Clearance (CL/F) for TAK-137_101 | Day 1 | CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-inf), expressed in liters per hour (L/hr). |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | Day 1 | Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax. |
| Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | Day 1 | Total amount of drug excreted in urine from time 0 to time t, calculated as Sum (Cu\*Vu), where Cu is the concentration of drug excreted in urine and Vu is the volume of urine excreted. |
| Fraction of TAK-137 Excreted in Urine (Fe) | Day 1 | Fraction of drug excreted in urine, calculated as Fe=(Ae\[0-t\]/dose)×100. |
| Renal Clearance (CLr) for TAK-137 | Day 1 | CLr is a measure of apparent clearance of the drug from the urine, calculated as CLr=Ae(0-t)/AUC(0-96). |
| Apparent Volume of Distribution (Vz/F) for TAK-137_101 | Day 1 | Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz. |
| Cmax: Maximum Observed Plasma Concentration for TAK-137 | Day 1 | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | Day 1 | (AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]). |
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 21 June 2013 to 30 January 2014.
Pre-assignment details
Healthy Volunteers were enrolled in a 6 Cohort randomized, dose escalating study at doses of 0.5, 2,5, 10 and 20 mg TAK-137 tablets or placebo single dose once in Cohorts 5,1,2,3 and 6 fasting respectively. Cohort 4 received 5 mg tablets or placebo single dose fasting then 5 mg or placebo fed.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: TAK-137 2 mg TAK-137 2 mg, tablets, orally, once on Day 1. | 6 |
| Cohort 2: TAK-137 5 mg TAK-137 5 mg, tablets, orally, once on Day 1. | 5 |
| Cohort 3: TAK-137 10 mg TAK-137 10 mg, tablets, orally, once on Day 1. | 6 |
| Cohort 4: TAK-137 5 mg Food Effect TAK-137 5 mg, tablets, orally, under fasted conditions, once on Day 1 of Period 1, followed by 14 days of follow-up, followed by TAK-137 5 mg, tablets, orally, under fed conditions, once on Day 1 of Period 2. | 6 |
| Cohort 5: TAK-137 0.5 mg TAK-137 0.5 mg, tablets, orally, once on Day 1. | 6 |
| Cohort 6: TAK-137 20 mg TAK-137 20 mg, tablets, orally, once on Day 1. | 6 |
| Cohorts 1-6: Placebo TAK-137 placebo-matching tablets, orally, once on Day 1. | 12 |
| Total | 47 |
Baseline characteristics
| Characteristic | Cohort 1: TAK-137 2 mg | Total | Cohorts 1-6: Placebo | Cohort 6: TAK-137 20 mg | Cohort 5: TAK-137 0.5 mg | Cohort 4: TAK-137 5 mg Food Effect | Cohort 3: TAK-137 10 mg | Cohort 2: TAK-137 5 mg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.8 years STANDARD_DEVIATION 9 | 34.9 years STANDARD_DEVIATION 9.43 | 31.5 years STANDARD_DEVIATION 6.87 | 38.5 years STANDARD_DEVIATION 10.63 | 24.7 years STANDARD_DEVIATION 3.88 | 36.5 years STANDARD_DEVIATION 9.27 | 40.5 years STANDARD_DEVIATION 8.22 | 34.0 years STANDARD_DEVIATION 8.66 |
| Alcohol Classification Current | 0 participants | 3 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants | 0 participants |
| Alcohol Classification Never | 6 participants | 44 participants | 12 participants | 6 participants | 6 participants | 5 participants | 4 participants | 5 participants |
| Body Mass Index (BMI) | 24.22 kg/m^2 STANDARD_DEVIATION 3.276 | 24.93 kg/m^2 STANDARD_DEVIATION 3.074 | 26.51 kg/m^2 STANDARD_DEVIATION 2.658 | 23.38 kg/m^2 STANDARD_DEVIATION 2.315 | 25.38 kg/m^2 STANDARD_DEVIATION 2.905 | 24.68 kg/m^2 STANDARD_DEVIATION 4.26 | 25.68 kg/m^2 STANDARD_DEVIATION 3.323 | 26.48 kg/m^2 STANDARD_DEVIATION 2.138 |
| Caffeine Consumption No | 6 participants | 35 participants | 7 participants | 5 participants | 5 participants | 4 participants | 4 participants | 4 participants |
| Caffeine Consumption Yes | 0 participants | 12 participants | 5 participants | 1 participants | 1 participants | 2 participants | 2 participants | 1 participants |
| Height | 170.3 cm STANDARD_DEVIATION 8.19 | 171.6 cm STANDARD_DEVIATION 9.52 | 166.2 cm STANDARD_DEVIATION 9.44 | 164.7 cm STANDARD_DEVIATION 11.74 | 171.5 cm STANDARD_DEVIATION 6.44 | 172.3 cm STANDARD_DEVIATION 8.62 | 178.0 cm STANDARD_DEVIATION 6.63 | 173.2 cm STANDARD_DEVIATION 13.22 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 4 participants | 2 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 1 participants | 19 participants | 5 participants | 3 participants | 3 participants | 2 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 participants | 15 participants | 3 participants | 1 participants | 3 participants | 1 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic or Latino | 3 participants | 32 participants | 9 participants | 5 participants | 3 participants | 5 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized White | 4 participants | 22 participants | 5 participants | 3 participants | 2 participants | 4 participants | 3 participants | 1 participants |
| Region of Enrollment United States | 6 participants | 47 participants | 12 participants | 6 participants | 6 participants | 6 participants | 6 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 20 Participants | 6 Participants | 5 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 27 Participants | 6 Participants | 1 Participants | 2 Participants | 4 Participants | 6 Participants | 4 Participants |
| Smoking Classification Ex-smoker | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants |
| Smoking Classification Never smoked | 6 participants | 46 participants | 12 participants | 6 participants | 6 participants | 5 participants | 6 participants | 5 participants |
| Weight | 70.97 kg STANDARD_DEVIATION 15.299 | 74.23 kg STANDARD_DEVIATION 15.306 | 73.23 kg STANDARD_DEVIATION 9.378 | 64.18 kg STANDARD_DEVIATION 14.297 | 75.05 kg STANDARD_DEVIATION 12.228 | 74.40 kg STANDARD_DEVIATION 18.84 | 81.88 kg STANDARD_DEVIATION 15.381 | 79.86 kg STANDARD_DEVIATION 14.87 |
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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 1 / 6 | 0 / 11 | 1 / 6 | 3 / 6 | 4 / 12 | 1 / 6 | 0 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 11 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 2 |
Outcome results
Primary
Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Day 1 to 14 days after the last dose of study medication(Up to 30 days)
Population: Safety population included all participants who received at least one dose of study medication. 8 of the 47 enrolled participants participated in Cohort 4 fed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-137 0.5 mg | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 16.7 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 16.7 percentage of participants |
| TAK-137 20 mg | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 50.0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 33.3 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 16.7 percentage of participants |
| Placebo (Fed) | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | 0 percentage of participants |
Primary
Percentage of Participants With Abnormal Safety Laboratory Findings
The percentage of participants with any markedly abnormal standard safety laboratory values was collected throughout study.
Time frame: Day 1 to 14 days after the last dose of study medication (Up to 30 Days)
Population: Participants from the Safety population, all participants who received at least one dose of study medication, with data available for analysis. 8 of the 47 enrolled participants participated in Cohort 4 fed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-137 0.5 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Abnormal Safety Laboratory Findings | 0 percentage of participants |
Primary
Percentage of Participants With Markedly Abnormal Vital Sign Measurements
The percentage of participants with any markedly abnormal standard vital sign measurements was collected throughout study.
Time frame: Day 1 to 14 days after the last dose of study medication
Population: Participants from the Safety population, all participants who received at least one dose of study medication, with data available for analysis. 8 of the 47 enrolled participants participated in Cohort 4 fed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 0.5 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 16.7 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 16.7 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 16.7 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 16.7 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 16.7 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 2 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 9.1 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fasting) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 16.7 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 16.7 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 10 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 16.7 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 16.7 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 16.7 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 50.0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 0 percentage of participants |
| TAK-137 20 mg | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 8.3 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 8.3 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 8.3 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 Placebo | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 16.7 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 16.7 percentage of participants |
| TAK-137 5 mg (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) <50 mmHg | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) >110 mmHg | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) <85 mmHG | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (3 min after standing) >110 mmHg | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) >120 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) <50 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) >180 mmHG | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (3 min after standing) <85 mmHG | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (1 min after standing) <50 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (1 min after standing) >180 mmHG | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) >180 mmHG | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (3 min after standing) >120 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Systolic BP (5 min after supine) <85 mmHG | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) <50 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (1 min after standing) <50 mmHg | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) >110 mmHg | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Pulse (5 min after supine) >120 bpm | 0 percentage of participants |
| Placebo (Fed) | Percentage of Participants With Markedly Abnormal Vital Sign Measurements | Diastolic BP (5 min after supine) <50 mmHg | 0 percentage of participants |
Secondary
Apparent Clearance (CL/F) for TAK-137_101
CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-inf), expressed in liters per hour (L/hr).
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Apparent Clearance (CL/F) for TAK-137_101 | 5.22 liters/hour | Standard Deviation 1.304 |
| TAK-137 2 mg | Apparent Clearance (CL/F) for TAK-137_101 | 3.66 liters/hour | Standard Deviation 1.912 |
| TAK-137 5 mg (Fasting) | Apparent Clearance (CL/F) for TAK-137_101 | 5.23 liters/hour | Standard Deviation 3.877 |
| TAK-137 10 mg | Apparent Clearance (CL/F) for TAK-137_101 | 5.91 liters/hour | Standard Deviation 3.372 |
| TAK-137 20 mg | Apparent Clearance (CL/F) for TAK-137_101 | 6.26 liters/hour | Standard Deviation 3.062 |
| TAK-137 Placebo | Apparent Clearance (CL/F) for TAK-137_101 | 7.19 liters/hour | Standard Deviation 6.976 |
| TAK-137 5 mg (Fed) | Apparent Clearance (CL/F) for TAK-137_101 | 3.63 liters/hour | Standard Deviation 0.996 |
Secondary
Apparent Volume of Distribution (Vz/F) for TAK-137_101
Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 48.57 liters | Standard Deviation 15.521 |
| TAK-137 2 mg | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 62.26 liters | Standard Deviation 23.596 |
| TAK-137 5 mg (Fasting) | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 81.23 liters | Standard Deviation 47.499 |
| TAK-137 10 mg | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 134.49 liters | Standard Deviation 150.393 |
| TAK-137 20 mg | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 62.85 liters | Standard Deviation 14.652 |
| TAK-137 Placebo | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 110.48 liters | Standard Deviation 86.222 |
| TAK-137 5 mg (Fed) | Apparent Volume of Distribution (Vz/F) for TAK-137_101 | 52.97 liters | Standard Deviation 17.267 |
Secondary
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137
AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 408 ng*hr/mL | Standard Deviation 121.64 |
| TAK-137 2 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 1696 ng*hr/mL | Standard Deviation 803.9 |
| TAK-137 5 mg (Fasting) | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 3135 ng*hr/mL | Standard Deviation 2380.8 |
| TAK-137 10 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 1198 ng*hr/mL | Standard Deviation 766.64 |
| TAK-137 20 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 97 ng*hr/mL | Standard Deviation 43.24 |
| TAK-137 Placebo | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 5353 ng*hr/mL | Standard Deviation 3295.2 |
| TAK-137 5 mg (Fed) | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-137 | 1474 ng*hr/mL | Standard Deviation 436.1 |
Secondary
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137
(AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 405 ng*hr/mL | Standard Deviation 121.6 |
| TAK-137 2 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 1668 ng*hr/mL | Standard Deviation 787.6 |
| TAK-137 5 mg (Fasting) | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 3012 ng*hr/mL | Standard Deviation 2204.1 |
| TAK-137 10 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 1191 ng*hr/mL | Standard Deviation 767.9 |
| TAK-137 20 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 94 ng*hr/mL | Standard Deviation 41.9 |
| TAK-137 Placebo | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 5346 ng*hr/mL | Standard Deviation 3292.4 |
| TAK-137 5 mg (Fed) | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-137 | 1470 ng*hr/mL | Standard Deviation 434.5 |
Secondary
Cmax: Maximum Observed Plasma Concentration for TAK-137
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 38.8 ng/mL | Standard Deviation 8.64 |
| TAK-137 2 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 68.90 ng/mL | Standard Deviation 7.4 |
| TAK-137 5 mg (Fasting) | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 121.1 ng/mL | Standard Deviation 28.44 |
| TAK-137 10 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 61.1 ng/mL | Standard Deviation 16.11 |
| TAK-137 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 9.0 ng/mL | Standard Deviation 0.76 |
| TAK-137 Placebo | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 206.1 ng/mL | Standard Deviation 80.72 |
| TAK-137 5 mg (Fed) | Cmax: Maximum Observed Plasma Concentration for TAK-137 | 85.9 ng/mL | Standard Deviation 28.58 |
Secondary
Fraction of TAK-137 Excreted in Urine (Fe)
Fraction of drug excreted in urine, calculated as Fe=(Ae\[0-t\]/dose)×100.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Fraction of TAK-137 Excreted in Urine (Fe) | 0.19 percent excreted | Standard Deviation 0.08 |
| TAK-137 2 mg | Fraction of TAK-137 Excreted in Urine (Fe) | 0.33 percent excreted | Standard Deviation 0.298 |
| TAK-137 5 mg (Fasting) | Fraction of TAK-137 Excreted in Urine (Fe) | 0.47 percent excreted | Standard Deviation 0.428 |
| TAK-137 10 mg | Fraction of TAK-137 Excreted in Urine (Fe) | 0.38 percent excreted | Standard Deviation 0.293 |
| TAK-137 20 mg | Fraction of TAK-137 Excreted in Urine (Fe) | 0.04 percent excreted | Standard Deviation 0.068 |
| TAK-137 Placebo | Fraction of TAK-137 Excreted in Urine (Fe) | 0.29 percent excreted | Standard Deviation 0.221 |
| TAK-137 5 mg (Fed) | Fraction of TAK-137 Excreted in Urine (Fe) | 0.43 percent excreted | Standard Deviation 0.267 |
Secondary
Renal Clearance (CLr) for TAK-137
CLr is a measure of apparent clearance of the drug from the urine, calculated as CLr=Ae(0-t)/AUC(0-96).
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Renal Clearance (CLr) for TAK-137 | 0.0093 liters/hour | Standard Deviation 0.00268 |
| TAK-137 2 mg | Renal Clearance (CLr) for TAK-137 | 0.0094 liters/hour | Standard Deviation 0.00577 |
| TAK-137 5 mg (Fasting) | Renal Clearance (CLr) for TAK-137 | 0.0138 liters/hour | Standard Deviation 0.00477 |
| TAK-137 10 mg | Renal Clearance (CLr) for TAK-137 | 0.0164 liters/hour | Standard Deviation 0.00626 |
| TAK-137 20 mg | Renal Clearance (CLr) for TAK-137 | 0.0031 liters/hour | Standard Deviation 0.005 |
| TAK-137 Placebo | Renal Clearance (CLr) for TAK-137 | 0.0117 liters/hour | Standard Deviation 0.00453 |
| TAK-137 5 mg (Fed) | Renal Clearance (CLr) for TAK-137 | 0.0150 liters/hour | Standard Deviation 0.00804 |
Secondary
Terminal Elimination Half-life (T1/2) for TAK-137_101
Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 6.65 hours | Standard Deviation 2.462 |
| TAK-137 2 mg | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 12.66 hours | Standard Deviation 2.491 |
| TAK-137 5 mg (Fasting) | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 13.60 hours | Standard Deviation 7.105 |
| TAK-137 10 mg | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 15.77 hours | Standard Deviation 10.553 |
| TAK-137 20 mg | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 8.54 hours | Standard Deviation 4.487 |
| TAK-137 Placebo | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 13.09 hours | Standard Deviation 5.276 |
| TAK-137 5 mg (Fed) | Terminal Elimination Half-life (T1/2) for TAK-137_101 | 10.52 hours | Standard Deviation 3.875 |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137
Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TAK-137 0.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 2.00 hours |
| TAK-137 2 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 3.00 hours |
| TAK-137 5 mg (Fasting) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 3.00 hours |
| TAK-137 10 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 2.50 hours |
| TAK-137 20 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 2.00 hours |
| TAK-137 Placebo | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 2.50 hours |
| TAK-137 5 mg (Fed) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-137 | 5.50 hours |
Secondary
Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t])
Total amount of drug excreted in urine from time 0 to time t, calculated as Sum (Cu\*Vu), where Cu is the concentration of drug excreted in urine and Vu is the volume of urine excreted.
Time frame: Day 1
Population: Participants from the Pharmacokinetic (PK) set, all participants who receive study drug and have at least one measureable concentration, with data available for analysis of this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-137 0.5 mg | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0039 mg | Standard Deviation 0.00161 |
| TAK-137 2 mg | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0164 mg | Standard Deviation 0.01492 |
| TAK-137 5 mg (Fasting) | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0470 mg | Standard Deviation 0.04281 |
| TAK-137 10 mg | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0192 mg | Standard Deviation 0.01465 |
| TAK-137 20 mg | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0002 mg | Standard Deviation 0.00034 |
| TAK-137 Placebo | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0585 mg | Standard Deviation 0.04417 |
| TAK-137 5 mg (Fed) | Total Amount of Drug (TAK-137) Excreted in Urine From Time 0 to Time t (Ae[0-t]) | 0.0217 mg | Standard Deviation 0.01335 |