Pediatric Hypertension
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the pharmacokinetics and safety of a single dose of TAK-536 (azilsartan) in pediatric patients aged 6 to less than 16 years with hypertension.
Detailed description
The drug being tested in this study is called azilsartan. Azilsartan was being tested to evaluate how it is processed by the body (pharmacokinetics). This study looked at lab results in pediatric participants who took azilsartan. The study enrolled 6 patients. Participants were assigned to study medication dose by body weight as follows: * Body Weight \<50 kg: azilsartan 5 mg * Body Weight ≥50 kg: azilsartan 10 mg All participants took a single oral dose of azilsartan on Day 1 of the study. This multi-center trial was conducted in Japan. The overall time to participate in this study was 17 days. Participants made multiple visits to the clinic, and were contacted by telephone on Day 6 and Day 15 after last dose of study drug for a follow-up assessment.
Interventions
DRUGAzilsartan
Azilsartan tablets
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
1. In the opinion of the investigator or subinvestigator, the participant's parent or legal guardian is capable of understanding and complying with the study requirements. 2. The participant's parent or legal guardian is capable of signing and dating a written informed consent form on behalf of the participant prior to the initiation of any study procedures. Written informed assent is also obtained from the participant as much as possible. 3. The participant is diagnosed as hypertensive (if the participant is not receiving antihypertensive therapy, the diagnosis will be based on the Age- and Gender-Based Blood Pressure Reference for Children. Sitting diastolic blood pressure \[DBP\] or systolic blood pressure \[SBP\] is to be in at least the 95th percentile if essential hypertension is present without concurrent hypertensive organ damage and at least the 90th percentile if secondary hypertension is present with concurrent chronic renal disease, diabetes mellitus, heart failure, or hypertensive organ damage). 4. The participant is male or female and aged 6 to less than 16 years at the time of consent. 5. The participant weighs at least 20 kg during the observation period. 6. The participant is capable of taking the tablets provided as study drug. 7. Participants after renal transplants should meet the following conditions: At least 6 months has elapsed from the transplant to the start of the observation period with stable graft function for more than 6 months (and estimated glomerular filtration rate \[eGFR\] ≥ 30 mL/min/1.73 m\^2) and historical documentation (Doppler echo or computed tomography \[CT\], magnetic resonance imaging \[MRI\], etc.) which verify that arterial stenosis is not present in the transplanted kidney. For participants receiving immunosuppressive therapy, the dose should have been stable at least 30 days before study drug administration. 8. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent to within 1 month after the completion of the study and have a negative pregnancy test result during the observation period.
Exclusion criteria
1. The participant received an investigational drug within 30 days prior to the start of the observation period or is currently participating in another clinical study or post-marketing study. Note: This does not apply to participants participating in observational studies without interventional or invasive therapy. 2. The participant is determined to have poorly controlled hypertension (as a general guideline, when clinical sitting blood pressure is measured, SBP is to be at least 15 mmHg higher and/or DBP is to be at least 10 mmHg higher than the 99th percentile in the Age- and Gender-Based Blood Pressure Reference for Children). 3. The participant is diagnosed with malignant hypertension or rapidly progressive hypertension. 4. The participant has severe renal dysfunction (eGFR \<30 mL/min/1.73 m\^2), dialysis treatment, renovascular disease affecting both kidneys or a solitary kidney, severe nephrotic syndrome not in remission, or serum albumin \<2.5 g/dL. 5. The participant has a history or clinical manifestations of serious cardiovascular, hepatobiliary, gastrointestinal, endocrine (e.g., hyperthyroidism and Cushing's syndrome), hematologic, immunologic, genitourinary, or psychiatric disease; cancer; and/or any conditions that would interfere with the health status of the participant through study participation or would jeopardize study integrity in the opinion of the investigator or subinvestigator. 6. The participant has left ventricular outflow tract obstruction affecting hemodynamics due to aortic stenosis, aortic valve disease, or the like or is scheduled to have surgery affecting blood pressure (e.g., repair of arterial anomalies) during the study. 7. The participant underwent a surgical procedure with major bleeding within 6 months before the start of the observation period. 8. The participant has past or present clinically significant abnormalities on the 12-lead electrocardiogram and is ineligible for the study in the opinion of the investigator or subinvestigator. 9. The participant has poorly controlled diabetes mellitus (hemoglobin A1c \[HbA1c\] \>9.0% during the observation period) 10. The participant has any of either alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] at least 2.5 times the upper limit of standard value or total bilirubin at least 1.5 times the upper limit of standard value, severe hepatic dysfunction, active liver disease (regardless of etiology), and jaundice during the observation period. 11. The participant has hyperkalemia exceeding the upper limit of standard value during the observation period. 12. The participant has a history of hepatitis B, hepatitis C, or human immunodeficiency virus infection at the start of the observation period. 13. The participant has a history of hypersensitivity or allergy to angiotensin II receptor blockers (ARBs). 14. The participant requires treatment with prohibited concomitant drug(s). 15. Peripheral venous blood collection from the participant is difficult. 16. The participant had a clinically significant acute disease within 30 days from the day before study drug administration. 17. If female, the participant is pregnant or lactating, or intending to become pregnant before giving consent, during the study period, or within 1 month after study completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) | Pre-dose and at multiple time points (up to 24 hours) post-dose | AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule. |
| Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) | Pre-dose and at multiple time points (up to 24 hours) post-dose | Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve. |
| AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) | Pre-dose and at multiple time points (up to 24 hours) post-dose | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) | Pre-dose and at multiple time points (up to 24 hours) post-dose | Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax. |
| T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) | Pre-dose and at multiple time points (up to 24 hours) post-dose | T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz. |
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-I | Pre-dose and at multiple time points (up to 24 hours) post-dose | AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule. |
| Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-I | Pre-dose and at multiple time points (up to 24 hours) post-dose | Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve. |
| AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-I | Pre-dose and at multiple time points (up to 24 hours) post-dose | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-I | Pre-dose and at multiple time points (up to 24 hours) post-dose | Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax. |
| T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-I | Pre-dose and at multiple time points (up to 24 hours) post-dose | T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz. |
| AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-II | Pre-dose and at multiple time points (up to 24 hours) post-dose | AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule. |
| Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-II | Pre-dose and at multiple time points (up to 24 hours) post-dose | Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve. |
| AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-II | Pre-dose and at multiple time points (up to 24 hours) post-dose | AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-II | Pre-dose and at multiple time points (up to 24 hours) post-dose | Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax. |
| T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-II | Pre-dose and at multiple time points (up to 24 hours) post-dose | T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz. |
| Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) | Day 1 from 0 to 24 hours post-dose | The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 will be calculated from the urinary concentration and volume of each participant. |
| Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-I | Day 1 from 0 to 24 hours post-dose | The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 metabolite M-I will be calculated from the urinary concentration and volume of each participant. |
| Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-II | Day 1 from 0 to 24 hours post-dose | The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 metabolite M-II will be calculated from the urinary concentration and volume of each participant. |
| Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Up to 15 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 (example, 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. Treatment emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. |
| Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Vital Signs | Baseline and Day 2 | Vital signs are defined as sitting blood pressure, sitting pulse rate and temperature. |
| Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Body Weight | Baseline and Day 2 | — |
| Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Resting 12-Lead Electrocardiogram (ECG) | Baseline and Day 2 | A resting 12-lead ECG was recorded. The investigator or subinvestigator (or a qualified physician at the study site) interpreted the ECG results. |
| Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Laboratory Test Results | Baseline and Day 2 | Laboratory test results are defined as serum chemistry, hematology and urinalysis. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 3 investigative sites in Japan from 6 August 2015 (first participant signed informed consent) to 10 September 2015.
Pre-assignment details
Participants with a diagnosis of hypertension were enrolled in 1 of 2 treatment groups, TAK-536 (azilsartan) 5 mg or 10 mg based on weight.
Participants by arm
| Arm | Count |
|---|---|
| Azilsartan 5 mg Weight \<50 kg: azilsartan 5 mg, tablets, orally, once, after breakfast on Day 1. | 3 |
| Azilsartan 10 mg Weight ≥50 kg: azilsartan 10 mg, tablets, orally, once, after breakfast on Day 1. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Azilsartan 5 mg | Azilsartan 10 mg | Total |
|---|---|---|---|
| Age, Continuous | 9.0 years STANDARD_DEVIATION 0 | 13.7 years STANDARD_DEVIATION 0.58 | 11.3 years STANDARD_DEVIATION 2.58 |
| Body Mass Index (BMI) | 15.93 kg/m^2 STANDARD_DEVIATION 0.651 | 24.77 kg/m^2 STANDARD_DEVIATION 2.108 | 20.35 kg/m^2 STANDARD_DEVIATION 5.035 |
| Caffeine Classification No | 3 participants | 3 participants | 6 participants |
| Caffeine Classification Yes | 0 participants | 0 participants | 0 participants |
| Disease Duration | 0.77 years STANDARD_DEVIATION 0.907 | 4.17 years STANDARD_DEVIATION 2.994 | 2.47 years STANDARD_DEVIATION 2.717 |
| Height | 131.0 cm STANDARD_DEVIATION 10.54 | 163.3 cm STANDARD_DEVIATION 7.37 | 147.2 cm STANDARD_DEVIATION 19.49 |
| Region of Enrollment Japan | 3 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
| Types of Hypertension Essential Hypertension | 0 participants | 1 participants | 1 participants |
| Types of Hypertension Secondary Hypertension | 3 participants | 2 participants | 5 participants |
| Weight | 27.53 kg STANDARD_DEVIATION 5.537 | 65.90 kg STANDARD_DEVIATION 2.955 | 46.72 kg STANDARD_DEVIATION 21.386 |
| Weight Categorical <50.0 kg | 3 participants | 0 participants | 3 participants |
| Weight Categorical ≥50.0 kg | 0 participants | 3 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan)
AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) | 6350.3 ng*hr/mL | Standard Deviation 2963.53 |
| Azilsartan 10 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) | 6871.7 ng*hr/mL | Standard Deviation 893.93 |
Primary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-I
AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-I | 1592.7 ng*hr/mL | Standard Deviation 379.29 |
| Azilsartan 10 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-I | 1420.5 ng*hr/mL | Standard Deviation 707.81 |
Primary
AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-II
AUC(0-24) is a measure of total plasma exposure to the drug from time 0 to 24 hours post-dose, calculated using the linear trapezoidal rule.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-II | 1986.5 ng*hr/mL | Standard Deviation 412.24 |
| Azilsartan 10 mg | AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to Time 24 Hours of TAK-536 (Azilsartan) Metabolite M-II | 3526.0 ng*hr/mL | — |
Primary
AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan)
AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) | 6635.7 ng*hr/mL | Standard Deviation 3279.58 |
| Azilsartan 10 mg | AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) | 7433.3 ng*hr/mL | Standard Deviation 1227.49 |
Primary
AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-I
AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-I | 1674.7 ng*hr/mL | Standard Deviation 403.91 |
| Azilsartan 10 mg | AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-I | 971.0 ng*hr/mL | — |
Primary
AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-II
AUC(0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity, calculated as AUC(0-inf)=AUC(0-tlqc)+lqc/λz.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Azilsartan 5 mg | AUC(0-inf) Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of TAK-536 (Azilsartan) Metabolite M-II | 1798.0 ng*hr/mL |
Primary
Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan)
Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) | 888.3 ng/mL | Standard Deviation 291.11 |
| Azilsartan 10 mg | Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) | 831.3 ng/mL | Standard Deviation 180.79 |
Primary
Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-I
Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-I | 191.3 ng/mL | Standard Deviation 31.39 |
| Azilsartan 10 mg | Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-I | 141.3 ng/mL | Standard Deviation 36.5 |
Primary
Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-II
Cmax is the maximum observed plasma concentration (actual measurement value) of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-II | 227.7 ng/mL | Standard Deviation 64.38 |
| Azilsartan 10 mg | Cmax: Maximum Observed Plasma Concentration of TAK-536 (Azilsartan) Metabolite M-II | 179.3 ng/mL | Standard Deviation 41.5 |
Primary
Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan)
The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 will be calculated from the urinary concentration and volume of each participant.
Time frame: Day 1 from 0 to 24 hours post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) | 6.640 percent of dose | Standard Deviation 2.9182 |
| Azilsartan 10 mg | Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) | 5.505 percent of dose | Standard Deviation 4.3654 |
Primary
Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-I
The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 metabolite M-I will be calculated from the urinary concentration and volume of each participant.
Time frame: Day 1 from 0 to 24 hours post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-I | 0.1348 percent of dose | Standard Deviation 0.20771 |
| Azilsartan 10 mg | Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-I | 0.000 percent of dose | Standard Deviation 0 |
Primary
Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-II
The cumulative urinary excretion ratio (% of dose \[TAK-536-equivalent\]) of TAK-536 metabolite M-II will be calculated from the urinary concentration and volume of each participant.
Time frame: Day 1 from 0 to 24 hours post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-II | 13.53 percent of dose | Standard Deviation 2.6839 |
| Azilsartan 10 mg | Cumulative Urinary Excretion Ratio of TAK-536 (Azilsartan) Metabolite M-II | 8.175 percent of dose | Standard Deviation 6.4689 |
Primary
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
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 (example, 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. Treatment emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Time frame: Up to 15 Days
Population: Safety population includes all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azilsartan 5 mg | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 1 participants |
| Azilsartan 5 mg | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 participants |
| Azilsartan 10 mg | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 0 participants |
| Azilsartan 10 mg | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 0 participants |
Primary
Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Body Weight
Time frame: Baseline and Day 2
Population: Safety population includes all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan 5 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Body Weight | 0 percentage of participants |
| Azilsartan 10 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Body Weight | 0 percentage of participants |
Primary
Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Laboratory Test Results
Laboratory test results are defined as serum chemistry, hematology and urinalysis.
Time frame: Baseline and Day 2
Population: Safety population includes all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan 5 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Laboratory Test Results | 0 percentage of participants |
| Azilsartan 10 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Laboratory Test Results | 0 percentage of participants |
Primary
Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Resting 12-Lead Electrocardiogram (ECG)
A resting 12-lead ECG was recorded. The investigator or subinvestigator (or a qualified physician at the study site) interpreted the ECG results.
Time frame: Baseline and Day 2
Population: Safety population includes all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan 5 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Resting 12-Lead Electrocardiogram (ECG) | 0 percentage of participants |
| Azilsartan 10 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Resting 12-Lead Electrocardiogram (ECG) | 0 percentage of participants |
Primary
Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Vital Signs
Vital signs are defined as sitting blood pressure, sitting pulse rate and temperature.
Time frame: Baseline and Day 2
Population: Safety population includes all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Azilsartan 5 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Vital Signs | 0 percentage of participants |
| Azilsartan 10 mg | Percentage of Participants With Remarkable Findings of Clinical Concern From Baseline in Vital Signs | 0 percentage of participants |
Primary
T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan)
T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) | 4.727 hours | Standard Deviation 1.0083 |
| Azilsartan 10 mg | T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) | 6.147 hours | Standard Deviation 0.67575 |
Primary
T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-I
T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Azilsartan 5 mg | T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-I | 5.437 hours | Standard Deviation 0.45938 |
| Azilsartan 10 mg | T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-I | 5.870 hours | — |
Primary
T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-II
T1/2 is the terminal elimination half-life (time required for half of the drug to be eliminated from the plasma), calculated as T1/2=ln(2)/λz.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Azilsartan 5 mg | T1/2: Terminal Elimination Half-Life of TAK-536 (Azilsartan) Metabolite M-II | 5.510 hours |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan)
Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azilsartan 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) | 3.00 hours |
| Azilsartan 10 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) | 4.00 hours |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-I
Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azilsartan 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-I | 3.00 hours |
| Azilsartan 10 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-I | 6.00 hours |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-II
Tmax is the time to reach Cmax (actual measurement value), equal to time (hours) to Cmax.
Time frame: Pre-dose and at multiple time points (up to 24 hours) post-dose
Population: PK population includes all participants who received the study drug without any major protocol deviation, and were evaluable for pharmacokinetics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Azilsartan 5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-II | 5.90 hours |
| Azilsartan 10 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of TAK-536 (Azilsartan) Metabolite M-II | 8.00 hours |