Japanese Healthy Adult Male Participants
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the bio-equivalence of a single oral administration of TAK-536 pediatric formulation (granules) in comparison with a TAK-536 commercial formulation (tablet) in Japanese healthy adult male participants in an open label, 2-period, 2-treatment, cross-over design.
Detailed description
The purpose of this study is to evaluate the bio-equivalence of a single oral administration of TAK-536 pediatric formulation (granules) in comparison with a TAK-536 commercial formulation (tablet) in healthy adult male participants in an open label, 2-period, 2-treatment, cross-over design.
Interventions
DRUGTAK-536
TAK-536 granules.
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 or sub-investigator, the participant is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form prior to the initiation of any study procedures. 3. Is a Japanese healthy adult male. 4. Aged 20 to 35 years, inclusive, at the time of informed consent. 5. Weighs at least 50.0 kilogram (kg), and has a body mass index (BMI) between 18.5 and 25.0 kilogram per square meter (kg/m\^2), inclusive, at Screening.
Exclusion criteria
1. Has suspected hypotension with associated physical findings, such as dizziness postural, facial pallor, or cold sweats based on evaluation/physical examination at Screening, on the day before the study drug administration (Day -1) in Period 1, or up to the study drug administration on the Period 1. 2. Has received any study drug within 16 weeks (112 days) prior to the study drug administration in Period 1. 3. Has received TAK-536 or TAK-491 in a previous clinical study or as a therapeutic agent. 4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results. 5. Has a known hypersensitivity to any component of the formulation of TAK-536 or any angiotensin II receptor blocker (ARB). 6. Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) at Screening. 7. 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 is unwilling to agree to abstain from alcohol and drugs throughout the study. 8. Has taken any excluded medication, supplements, dietary products, or food products during the time periods specified in the protocol. 9. Has any current or recent (within 6 months) gastrointestinal diseases that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention). 10. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1. 11. 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. 12. Has poor peripheral venous access. 13. Has undergone whole blood collection of at least 200 milliliter (mL) within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of the study drug administration in Period 1. 14. Has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of the study drug administration in Period 1. 15. Has undergone blood component collection within 2 weeks (14 days) prior to the start of the study drug administration in Period 1. 16. Has an abnormal (clinically significant) ECG at Screening or prior to the study drug administration in Period 1. 17. Has abnormal laboratory values that suggest a clinically significant underlying disease, or participant with the following laboratory abnormalities at Screening or prior to the study drug administration in Period 1: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than (\>) 1.5 \* the upper limits of normal (ULN). 18. Who, in the opinion of the investigator or sub-investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-536 | Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours) |
| Cmax: Maximum Observed Plasma Concentration for TAK-536 | Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-536 | Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours) | — |
| Terminal Disposition Phase Rate Constant (λz) for TAK-536 | Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours) | — |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 6 of Intervention Period 2 (Day 18) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with this treatment or study participation. An AE can therefore be any unfavorable and unintended sign (for example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study participation, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536 | Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours) | — |
| Number of Participants With TEAEs Related to Body Weight | Baseline up to Day 6 of Intervention Period 2 (Day 18) | — |
| Number of Participants With TEAEs Related to Electrocardiograms (ECGs) | Baseline up to Day 6 of Intervention Period 2 (Day 18) | — |
| Number of Participants With TEAEs Related to Clinical Laboratory Tests | Baseline up to Day 6 of Intervention Period 2 (Day 18) | — |
| Number of Participants With TEAEs Related to Vital Signs | Baseline up to Day 6 of Intervention Period 2 (Day 18) | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536 | Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours) | — |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Japan from 10 February 2017 to 11 March 2017.
Pre-assignment details
Healthy male participants were enrolled in 1 of the 2 treatment sequences of this 2-period cross-over study to receive TAK-536 10 milligram (mg) granules (pediatric formulation) or TAK-536 10 mg tablet (commercial formulation).
Participants by arm
| Arm | Count |
|---|---|
| TAK-536 Granules + TAK-536 Tablet TAK-536 10 mg, granules (pediatric formulation), under fasted condition, orally, once on Day 1 of Intervention Period 1, followed by a Washout Period of at least 6 days, further followed by TAK-536 10 mg, tablet (commercial formulation), under fasted condition, orally, once on Day 1 of Intervention Period 2. | 7 |
| TAK-536 Tablet + TAK-536 Granules TAK-536 10 mg, tablet (commercial formulation), under fasted condition, orally, once on Day 1 of Intervention Period 1, followed by a Washout Period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), under fasted condition, orally, once on Day 1 of Intervention Period 2. | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | TAK-536 Granules + TAK-536 Tablet | Total | TAK-536 Tablet + TAK-536 Granules |
|---|---|---|---|
| Age, Continuous | 21.3 years STANDARD_DEVIATION 0.95 | 21.3 years STANDARD_DEVIATION 1.14 | 21.3 years STANDARD_DEVIATION 1.38 |
| Alcohol classification Drank a few times per month | 4 Participants | 7 Participants | 3 Participants |
| Alcohol classification Drank a few times per week | 1 Participants | 3 Participants | 2 Participants |
| Alcohol classification Never drank | 2 Participants | 4 Participants | 2 Participants |
| Body Mass Index (BMI) | 21.33 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.072 | 20.97 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.06 | 20.61 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.143 |
| Caffeine classification Had caffeine consumption | 1 Participants | 3 Participants | 2 Participants |
| Caffeine classification Had no caffeine consumption | 6 Participants | 11 Participants | 5 Participants |
| Height | 167.7 centimeter (cm) STANDARD_DEVIATION 3.64 | 169.5 centimeter (cm) STANDARD_DEVIATION 4.31 | 171.3 centimeter (cm) STANDARD_DEVIATION 4.42 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Japan | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
| Smoking classification Current smoker | 1 Participants | 4 Participants | 3 Participants |
| Smoking classification Ex-smoker | 1 Participants | 1 Participants | 0 Participants |
| Smoking classification Never smoked | 5 Participants | 9 Participants | 4 Participants |
| Weight | 59.97 kilogram (kg) STANDARD_DEVIATION 5.586 | 60.23 kilogram (kg) STANDARD_DEVIATION 6.005 | 60.49 kilogram (kg) STANDARD_DEVIATION 6.838 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-536
Time frame: Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Population: The pharmacokinetic (PK) analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-536 | 6053.7 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 1119.6 |
| TAK-536 10 mg Tablet (Commercial Formulation) | AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for TAK-536 | 6479.6 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 1008 |
90% CI: [-0.1088, -0.0373]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-536
Time frame: Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Population: The PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Cmax: Maximum Observed Plasma Concentration for TAK-536 | 803.3 nanogram per milliliter (ng/mL) | Standard Deviation 113.63 |
| TAK-536 10 mg Tablet (Commercial Formulation) | Cmax: Maximum Observed Plasma Concentration for TAK-536 | 878.1 nanogram per milliliter (ng/mL) | Standard Deviation 117.88 |
90% CI: [-0.1573, -0.0244]
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536
Time frame: Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Population: The PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536 | 6187.4 h*ng/mL | Standard Deviation 1167.72 |
| TAK-536 10 mg Tablet (Commercial Formulation) | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-536 | 6627.4 h*ng/mL | Standard Deviation 1061.66 |
Secondary
MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-536
Time frame: Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Population: The PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-536 | 9.781 hours | Standard Deviation 1.401 |
| TAK-536 10 mg Tablet (Commercial Formulation) | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-536 | 10.11 hours | Standard Deviation 1.1873 |
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study; it does not necessarily have to have a causal relationship with this treatment or study participation. An AE can therefore be any unfavorable and unintended sign (for example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study participation, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Baseline up to Day 6 of Intervention Period 2 (Day 18)
Population: The safety analysis set included all participants who received the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
| TAK-536 10 mg Tablet (Commercial Formulation) | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Body Weight
Time frame: Baseline up to Day 6 of Intervention Period 2 (Day 18)
Population: The safety analysis set included all the participants who received the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Number of Participants With TEAEs Related to Body Weight | 0 Participants |
| TAK-536 10 mg Tablet (Commercial Formulation) | Number of Participants With TEAEs Related to Body Weight | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Clinical Laboratory Tests
Time frame: Baseline up to Day 6 of Intervention Period 2 (Day 18)
Population: The safety analysis set included all the participants who received the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
| TAK-536 10 mg Tablet (Commercial Formulation) | Number of Participants With TEAEs Related to Clinical Laboratory Tests | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Electrocardiograms (ECGs)
Time frame: Baseline up to Day 6 of Intervention Period 2 (Day 18)
Population: The safety analysis set included all the participants who received the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Number of Participants With TEAEs Related to Electrocardiograms (ECGs) | 0 Participants |
| TAK-536 10 mg Tablet (Commercial Formulation) | Number of Participants With TEAEs Related to Electrocardiograms (ECGs) | 0 Participants |
Secondary
Number of Participants With TEAEs Related to Vital Signs
Time frame: Baseline up to Day 6 of Intervention Period 2 (Day 18)
Population: The safety analysis set included all the participants who received the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
| TAK-536 10 mg Tablet (Commercial Formulation) | Number of Participants With TEAEs Related to Vital Signs | 0 Participants |
Secondary
Terminal Disposition Phase Rate Constant (λz) for TAK-536
Time frame: Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Population: The PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Terminal Disposition Phase Rate Constant (λz) for TAK-536 | 0.06866 liter per hour (L/h) | Standard Deviation 0.0046324 |
| TAK-536 10 mg Tablet (Commercial Formulation) | Terminal Disposition Phase Rate Constant (λz) for TAK-536 | 0.06862 liter per hour (L/h) | Standard Deviation 0.0077457 |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536
Time frame: Day 1 pre-dose and at multiple time points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, and 48 hours post-dose; up to 48 hours)
Population: The PK analysis set included all participants who received the study drug, completed the minimum protocol-specified procedures without any major protocol deviations, and were evaluable for PK.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAK-536 10 mg Granules (Pediatric Formulation) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536 | 1.89 hours | Standard Deviation 0.738 |
| TAK-536 10 mg Tablet (Commercial Formulation) | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-536 | 2.43 hours | Standard Deviation 0.958 |