Hypertension
Conditions
Keywords
Pharmacological therapy
Brief summary
This is a phase 1, randomized, open-label, crossover study to evaluate the food-effect of single oral dose of TAK-536TCH final formulation tablet in healthy adult male participants.
Detailed description
The purpose of this study is to evaluate the food effect on the pharmacokinetics and safety of a single oral dose of TAK-536TCH under fasted and fed conditions in the morning in healthy adult male participants.
Interventions
DRUGTAK-536TCH
TAK-536TCH tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* 1\. In the opinion of the investigator and subinvestigator, the participant is capable of understanding and complying with protocol requirements. 2\. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures. 3\. The participant is a healthy Japanese adult male. 4. The participant is aged 20 to 35 years, inclusive at the time of informed consent. 5\. The participant weighs at least 50.0 kg and has a body mass index (BMI) from 18.5 to 25.0 kilograms per square meter (kg/m\^2), inclusive at Screening.
Exclusion criteria
1. Participant has systolic blood pressure less-than (\<) 90 millimeters of mercury (mmHg) at Screening. 2. Participant has suspected hypotension and associated physical findings, such as dizziness postural, facial pallor, or cold sweats based on evaluation/physical examination at Screening, on Day -1 of Period 1, or up to administration on the Period 1. 3. The participant has received any study drug within 16 weeks (that is \[i.e.\], 112 days) prior to study drug administration of Period 1. 4. The participant has received TAK-491\*, TAK-536, amlodipine, or hydrochlorothiazide in a previous clinical study or as a therapeutic agent. 5. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, or endocrine disease, or other abnormality (other than the disease studied), which could impact the ability of the participant to participate or potentially confound the study results. 6. Participant has a known hypersensitivity to drugs. 7. Participant has a positive urine drug result for drugs of abuse at Screening. 8. Participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit or was unwilling to agree to abstain from alcohol and drugs throughout the study. 9. Participant required any prohibited concomitant drugs, vitamins, or food products listed in the prohibited concomitant drugs and foods table. 10. Participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention \[e.g., cholecystectomy\]). 11. Participant has a history of cancer. 12. Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological reactions for syphilis at Screening. 13. Participant has poor peripheral venous access. 14. Participant has undergone whole blood collection of at least 200 mL within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to study drug administration in Period 1. 15. Participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to study drug administration in Period 1. 16. Participant has undergone blood component collection within 2 weeks (14 days) prior to study drug administration in Period 1. 17. Participant has a hemoglobin value of less than 12.5 g/dL in laboratory testing at Screening or prior to study drug administration in Period 1. 18. Participant has a clinically significant ECG abnormality at Screening or prior to study drug administration in Period 1. 19. Participant has abnormal laboratory values at Screening or prior to study drug administration of Period 1 that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is \>1.5-fold the upper limits of normal range. 20. Participant who, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Excretion Ratio of AML | Day 1: predose and at multiple time-points (up to 120 hours) postdose in each period | Urinary excretion ratio (% of dose) of AML in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected in each pooling period. |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | Day 1: predose and at multiple time points (up to 48 hours) postdose in each period | AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]). |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for AML | Day 1: predose and at multiple time points (up to 120 hours) postdose in each period | AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]). |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | Day 1: predose and at multiple time points (up to 48 hours) postdose in each period | AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for AML | Day 1: predose and at multiple time points (up to 120 hours) postdose in each period | AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity. |
| Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | Day 1: predose and at multiple time-points (up to 48 hours) postdose in each period | Urinary excretion ratio (percent \[%\] of dose) of TAK-536, its metabolite M-I, M-II and HCTZ in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected in each pooling period. |
| Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | Day 1: predose and at multiple time points (up to 48 hours) postdose in each period | — |
| Cmax: Maximum Plasma Concentration for Amlodipine Besilate (AML) | Day 1: predose and at multiple time points (up to 120 hours) postdose in each period | — |
| AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | Day 1: predose and at multiple time points (up to 48 hours) postdose in each period | AUC(0-48) is a measure of the area under the plasma concentration time-curve from time 0 to 48 hours postdose. |
| AUC(0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Postdose in Each Period for AML | Day 1: predose and at multiple time points (up to 120 hours) postdose in each period | AUC(0-120) is a measure of the area under the plasma concentration time-curve from time 0 to 120 hours postdose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 ) | — |
| Number of Participants With TEAEs Related to Vital Signs | Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 ) | — |
| Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 ) | — |
| Number of Participants With Clinical Significant Findings in Electrocardiograms After Study Drug Administration | Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 ) | Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measurement. |
| Number of Participants With TEAEs Related to Body Weight | Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 ) | — |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Japan from 29 January 2015 to 11 March 2015.
Pre-assignment details
Healthy adult male participants were enrolled in 1 of 2 treatment sequences in either of the Periods 1 or 2: Sequence A: TAK-536TCH (combination drug of TAK-536 \[azilsartan\], amlodipine besilate \[AML\], hydrochlorothiazide \[HTZ\]) Fasted in Period 1+ TAK-536TCH Fed in period 2; Sequence B: TAK-536TCH Fed in Period 1+ TAK-536TCH Fasted in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who received either 1 of the two treatment sequences: Sequence 1: TAK-536TCH (20 mg/5 mg/12.5 mg), tablet, in fasted condition, orally, once on Day 1 in Period 1, followed by 22 days washout period, followed by TAK-536TCH (20 mg/5 mg/12.5 mg), tablet, in fed condition, orally, once on Day 1 in Period 2 or Sequence 2: TAK-536TCH (20 mg/5 mg/12.5 mg), tablet, in fed condition, orally, once on Day 1 in Period 1, followed by 22 days washout period, followed by TAK-536TCH (20 mg/5 mg/12.5 mg), tablet, in fasted condition, orally, once on Day 1 in Period 2. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 22.2 years STANDARD_DEVIATION 3.54 |
| Alcohol Classification Drinks a few Days per Month | 7 participants |
| Alcohol Classification Had Never Drunk | 5 participants |
| Body Mass Index (BMI) | 20.85 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.499 |
| Caffeine Classification Caffeine Consumer | 1 participants |
| Caffeine Classification Caffeine Non-Consumer | 11 participants |
| Height | 171.3 centimeter (cm) STANDARD_DEVIATION 6.03 |
| Region of Enrollment Japan | 12 participants |
| Sex/Gender, Customized Male | 12 participants |
| Smoking Classification Current Smoker | 3 participants |
| Smoking Classification Ex-Smoker | 3 participants |
| Smoking Classification Never Smoked | 6 participants |
| Weight | 61.18 kilogram (kg) STANDARD_DEVIATION 5.548 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
AUC(0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Postdose in Each Period for AML
AUC(0-120) is a measure of the area under the plasma concentration time-curve from time 0 to 120 hours postdose.
Time frame: Day 1: predose and at multiple time points (up to 120 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536TCH Fasted | AUC(0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Postdose in Each Period for AML | 119.370 ng*hr/mL | Standard Deviation 27.7395 |
| TAK-536TCH Fed | AUC(0-120): Area Under the Plasma Concentration-Time Curve From Time 0 to 120 Hours Postdose in Each Period for AML | 125.749 ng*hr/mL | Standard Deviation 26.9893 |
Primary
AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ
AUC(0-48) is a measure of the area under the plasma concentration time-curve from time 0 to 48 hours postdose.
Time frame: Day 1: predose and at multiple time points (up to 48 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-536TCH Fasted | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 14599.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2254.31 |
| TAK-536TCH Fasted | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 9093.3 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1711.69 |
| TAK-536TCH Fasted | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 670.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 75.912 |
| TAK-536TCH Fasted | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 3215.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 698.75 |
| TAK-536TCH Fed | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 595.2 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 68.915 |
| TAK-536TCH Fed | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 13279.4 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2889.22 |
| TAK-536TCH Fed | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 2693.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 706.41 |
| TAK-536TCH Fed | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 8990.8 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 2310.99 |
Primary
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for AML
AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Time frame: Day 1: predose and at multiple time points (up to 120 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536TCH Fasted | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for AML | 132.941 ng*hr/mL | Standard Deviation 37.5121 |
| TAK-536TCH Fed | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for AML | 140.484 ng*hr/mL | Standard Deviation 34.4402 |
Primary
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ
AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.
Time frame: Day 1: predose and at multiple time points (up to 48 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-536TCH Fasted | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 15077.4 ng*hr/mL | Standard Deviation 2433.01 |
| TAK-536TCH Fasted | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 3271.3 ng*hr/mL | Standard Deviation 708.48 |
| TAK-536TCH Fasted | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 10496.0 ng*hr/mL | Standard Deviation 2221.49 |
| TAK-536TCH Fasted | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 673.5 ng*hr/mL | Standard Deviation 87.075 |
| TAK-536TCH Fed | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 595.9 ng*hr/mL | Standard Deviation 69.847 |
| TAK-536TCH Fed | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 13700.9 ng*hr/mL | Standard Deviation 3154.23 |
| TAK-536TCH Fed | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 10193.0 ng*hr/mL | Standard Deviation 2804.33 |
| TAK-536TCH Fed | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 2755.1 ng*hr/mL | Standard Deviation 727.37 |
Primary
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for AML
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: predose and at multiple time points (up to 120 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536TCH Fasted | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for AML | 119.370 ng*hr/mL | Standard Deviation 27.7395 |
| TAK-536TCH Fed | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for AML | 125.749 ng*hr/mL | Standard Deviation 26.9893 |
Primary
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ
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: predose and at multiple time points (up to 48 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-536TCH Fasted | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 14599.8 ng*hr/mL | Standard Deviation 2254.31 |
| TAK-536TCH Fasted | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 3215.8 ng*hr/mL | Standard Deviation 698.75 |
| TAK-536TCH Fasted | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 9093.3 ng*hr/mL | Standard Deviation 1711.69 |
| TAK-536TCH Fasted | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 641.3 ng*hr/mL | Standard Deviation 87.752 |
| TAK-536TCH Fed | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 556.4 ng*hr/mL | Standard Deviation 70.514 |
| TAK-536TCH Fed | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 13279.4 ng*hr/mL | Standard Deviation 2889.22 |
| TAK-536TCH Fed | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 8990.8 ng*hr/mL | Standard Deviation 2310.99 |
| TAK-536TCH Fed | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Each Period for TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 2693.8 ng*hr/mL | Standard Deviation 706.41 |
Primary
Cmax: Maximum Plasma Concentration for Amlodipine Besilate (AML)
Time frame: Day 1: predose and at multiple time points (up to 120 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536TCH Fasted | Cmax: Maximum Plasma Concentration for Amlodipine Besilate (AML) | 3.752 ng/mL | Standard Deviation 0.5124 |
| TAK-536TCH Fed | Cmax: Maximum Plasma Concentration for Amlodipine Besilate (AML) | 3.668 ng/mL | Standard Deviation 0.6468 |
Primary
Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ)
Time frame: Day 1: predose and at multiple time points (up to 48 hours) postdose in each period
Population: Pharmacokinetic (PK) analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAK-536TCH Fasted | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | TAK-536 | 1912.0 nanogram per milliliter (ng/mL) | Standard Deviation 253.39 |
| TAK-536TCH Fasted | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | M-I | 448.3 nanogram per milliliter (ng/mL) | Standard Deviation 143.36 |
| TAK-536TCH Fasted | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | M-II | 453.5 nanogram per milliliter (ng/mL) | Standard Deviation 109.75 |
| TAK-536TCH Fasted | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | HCTZ | 119.4 nanogram per milliliter (ng/mL) | Standard Deviation 30.481 |
| TAK-536TCH Fed | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | HCTZ | 101.6 nanogram per milliliter (ng/mL) | Standard Deviation 14.7 |
| TAK-536TCH Fed | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | TAK-536 | 1783.7 nanogram per milliliter (ng/mL) | Standard Deviation 318.16 |
| TAK-536TCH Fed | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | M-II | 451.9 nanogram per milliliter (ng/mL) | Standard Deviation 101.18 |
| TAK-536TCH Fed | Cmax: Maximum Plasma Concentration for TAK-536, Its Metabolites (M-I and M-II) and Hydrochlorothiazide (HCTZ) | M-I | 455.3 nanogram per milliliter (ng/mL) | Standard Deviation 131.68 |
Primary
Urinary Excretion Ratio of AML
Urinary excretion ratio (% of dose) of AML in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected in each pooling period.
Time frame: Day 1: predose and at multiple time-points (up to 120 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-536TCH Fasted | Urinary Excretion Ratio of AML | 6.843 percentage of dose |
| TAK-536TCH Fed | Urinary Excretion Ratio of AML | 7.328 percentage of dose |
Primary
Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ
Urinary excretion ratio (percent \[%\] of dose) of TAK-536, its metabolite M-I, M-II and HCTZ in urine were calculated for each participant. Ratio was calculated from the urine concentrations of each analyte and the volume of urine collected in each pooling period.
Time frame: Day 1: predose and at multiple time-points (up to 48 hours) postdose in each period
Population: PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and who were evaluable for the food-effect.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-536TCH Fasted | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 0.076 percentage of dose |
| TAK-536TCH Fasted | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 13.682 percentage of dose |
| TAK-536TCH Fasted | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 19.275 percentage of dose |
| TAK-536TCH Fasted | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 73.742 percentage of dose |
| TAK-536TCH Fed | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | HCTZ | 74.042 percentage of dose |
| TAK-536TCH Fed | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-I | 0.033 percentage of dose |
| TAK-536TCH Fed | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | M-II | 19.933 percentage of dose |
| TAK-536TCH Fed | Urinary Excretion Ratio of TAK-536, Its Metabolites (M-I and M-II) and HCTZ | TAK-536 | 13.080 percentage of dose |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Population: Safety analysis set included all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-536TCH Fasted | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 participants |
| TAK-536TCH Fed | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 1 participants |
Secondary
Number of Participants With Clinical Significant Findings in Electrocardiograms After Study Drug Administration
Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measurement.
Time frame: Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Population: Safety analysis set included all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-536TCH Fasted | Number of Participants With Clinical Significant Findings in Electrocardiograms After Study Drug Administration | 0 participants |
| TAK-536TCH Fed | Number of Participants With Clinical Significant Findings in Electrocardiograms After Study Drug Administration | 0 participants |
Secondary
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values
Time frame: Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Population: Safety analysis set included all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-536TCH Fasted | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | 1 participants |
| TAK-536TCH Fed | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | 0 participants |
Secondary
Number of Participants With TEAEs Related to Body Weight
Time frame: Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Population: Safety analysis set included all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-536TCH Fasted | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| TAK-536TCH Fed | Number of Participants With TEAEs Related to Body Weight | 0 participants |
Secondary
Number of Participants With TEAEs Related to Vital Signs
Time frame: Baseline up to 14 days after last dose of study drug (14 days after Day 1 of Period 2 )
Population: Safety analysis set included all participants who received the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-536TCH Fasted | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| TAK-536TCH Fed | Number of Participants With TEAEs Related to Vital Signs | 0 participants |