Japanese Healthy Adult Males
Conditions
Brief summary
The purpose of this study is to evaluate the bioequivalence of a single oral dose of 2 different drug forms of TAK-536 pediatric formulation and a single oral dose of TAK-536 commercial tablet in healthy Japanese adult male participants.
Detailed description
This study was designed to evaluate the bioequivalence of a single oral dose of 2 different drug forms of TAK-536 pediatric formulation (dry syrup, granules) and a single oral dose of TAK-536 commercial tablet by using open-label, 2 × 2 crossover design.
Interventions
DRUGTAK-536 Tablet
TAK-536 10 mg tablet
DRUGTAK-536 Dry Syrup Formulation
TAK-536 dry syrup formulation
DRUGTAK-536 Ganule Formulation
TAK-536 granule formulation
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 the sub-investigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant signs and dates a written, informed consent form (ICF) and any required privacy authorization prior to the initiation of any study procedures. 3. The participant is a healthy Japanese adult male volunteer. 4. The participant is between 20 and 35 years of age at the time of informed consent. 5. The participant has a body weight of at least 50.0 kilogram (kg) and has a body mass index (BMI) between 18.5 and 25.0 kilogram per meter square (kg/m\^2) at the time of screening.
Exclusion criteria
1. The participant has shown symptoms of dizziness on standing up, facial pallor, cold sweat, etc, and suspected hypotension at medical examination/physical findings at screening and the day before administration of the study drug for Period 1, and before administration of the study drug for Period 1. 2. The participant has received any investigational compound within 16 weeks (112 days) prior to the start of study medication for Period 1 3. The participant has received TAK-536 or TAK-491 in a previous clinical study or as a therapeutic agent. 4. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results. 5. The participant has a known hypersensitivity to TAK-536 or angiotensin II receptor blockers. 6. The participant has positive results in the urine drug screening test at screening. 7. The 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 or is unwilling to agree to abstain from alcohol and drugs throughout the study period. 8. The participant has taken any excluded medication, supplements, or food products during the time periods. 9. The participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent \[more than once per week\] occurrence of heartburn, or any surgical intervention (ie, cholecystectomy). 10. The participant has a history of cancer. 11. The 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. 12. The participant has poor peripheral venous access. 13. The 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 the start of study medication administration for Period 1. 14. The participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the start of study medication administration for Period 1. 15. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of study medication administration for Period 1. 16. The participant has an abnormal (clinically significant) electro-cardiogram at screening or prior to the start of study medication for Period 1. 17. The participant has abnormal laboratory values at screening or prior to the start of study medication for Period 1 that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine transaminase (ALT) or aspartate transaminase (AST) greater than (\>)1.5 times the upper limits of normal. 18. The participant who, in the opinion of the investigator or the 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 in Dry Syrup Cohort | Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-536 in Dry Syrup Cohort | Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose |
| AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Granule Cohort | Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-536 in Granule Cohort | Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Baseline up to Day 6 of Intervention Period 2 |
| Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | Baseline up to Day 6 of Intervention Period 2 |
| Number of Participants With TEAEs Related to Vital Signs | Baseline up to Day 6 of Intervention Period 2 |
| Number of Participants With TEAEs Related to Body Weight | Baseline up to Day 6 of Intervention Period 2 |
| Number of Participants Who Had Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) | Baseline up to Day 6 of Intervention Period 2 |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Japan from 25 March 2015 to 26 May 2015.
Pre-assignment details
Healthy participants were enrolled in 1 of 2 treatment sequences: Sequence a (dry syrup): TAK-536 dry syrup followed by TAK-536 tablet; Sequence b (dry syrup): TAK-536 tablet followed by TAK-536 dry syrup; Sequence a (granules): TAK-536 granules followed by TAK-536 tablet; Sequence b (granules): TAK-536 tablet followed by TAK-536 granules.
Participants by arm
| Arm | Count |
|---|---|
| Dry Syrup Cohort: TAK-536 Dry Syrup + TAK-536 Tablet Participants in Sequence a of dry syrup formulation received TAK-536 10 milligram (mg), dry syrup (pediatric formulation), orally, once on Day 1 of Intervention Period 1 (6 days), followed by washout period of at least 6 days, further followed by TAK-536 10 mg, tablet (commercial formulation), orally, once on Day 1 of Intervention Period 2 (6 days). | 13 |
| Dry Syrup Cohort: TAK-536 Tablet + TAK-536 Dry Syrup Participants in Sequence b of dry syrup formulation received TAK-536 10 mg, tablet (commercial formulation), orally, once on Day 1 of Intervention Period 1 (6 days), followed by washout period of at least 6 days, further followed by TAK-536 10 mg, dry syrup (pediatric formulation), orally, once on Day 1 of Intervention Period 2 (6 days). | 13 |
| Granule Cohort: TAK-536 Granules + TAK-536 Tablet Participants in Sequence a of granules formulation received TAK-536 10 mg, granules (pediatric formulation), orally, once on Day 1 of Intervention Period 1 (6 days), followed by washout period of at least 6 days, further followed by TAK-536 10 mg, tablet (commercial formulation), orally, once on Day 1 of Intervention Period 2 (6 days). | 13 |
| Granule Cohort: TAK-536 Tablet + TAK-536 Granules Participants in Sequence b of granules formulation received TAK-536 10 mg, tablet (commercial formulation), orally, once on Day 1 of Intervention Period 1 (6 days) followed by washout period of at least 6 days, further followed by TAK-536 10 mg, granules (pediatric formulation), orally, once on Day 1 of Intervention Period 2 (6 days). | 13 |
| Total | 52 |
Baseline characteristics
| Characteristic | Dry Syrup Cohort: TAK-536 Dry Syrup + TAK-536 Tablet | Dry Syrup Cohort: TAK-536 Tablet + TAK-536 Dry Syrup | Granule Cohort: TAK-536 Granules + TAK-536 Tablet | Granule Cohort: TAK-536 Tablet + TAK-536 Granules | Total |
|---|---|---|---|---|---|
| Age, Continuous | 25.3 years STANDARD_DEVIATION 2.21 | 25.9 years STANDARD_DEVIATION 4.11 | 26.6 years STANDARD_DEVIATION 4.07 | 27.4 years STANDARD_DEVIATION 5.71 | 26.308 years STANDARD_DEVIATION 4.16 |
| Alcohol classification Drank a few days per month | 1 participants | 3 participants | 3 participants | 3 participants | 10 participants |
| Alcohol classification Drank a few days per week | 1 participants | 2 participants | 2 participants | 0 participants | 5 participants |
| Alcohol classification Never drank | 11 participants | 8 participants | 8 participants | 10 participants | 37 participants |
| Caffeine Classification Had caffeine consumption | 2 participants | 3 participants | 6 participants | 5 participants | 16 participants |
| Caffeine Classification Had no caffeine consumption | 11 participants | 10 participants | 7 participants | 8 participants | 36 participants |
| Sex/Gender, Customized Male | 13 participants | 13 participants | 13 participants | 13 participants | 52 participants |
| Smoking classification Current smoker | 0 participants | 0 participants | 1 participants | 1 participants | 2 participants |
| Smoking classification Ex-smoker | 6 participants | 4 participants | 5 participants | 4 participants | 19 participants |
| Smoking classification Never smoked | 7 participants | 9 participants | 7 participants | 8 participants | 31 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 26 | 5 / 26 | 0 / 26 | 3 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 | 0 / 26 | 0 / 26 |
Outcome results
Primary
AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Dry Syrup Cohort
Time frame: Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The pharmacokinetic 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 pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Dry Syrup Cohort | 7065.6 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1317.91 |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Dry Syrup Cohort | 7341.2 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 1493.71 |
Comparison: Based on the analysis of variance (ANOVA) in which the natural logarithms of AUC(0-48) of TAK-536 were used as dependent variables, and formulation, sequence (administration order) and administration period were used as fixed effects, bioequivalence was assessed providing two-sided 90% confidence intervals (CIs) for the differences between the formulations and between the periods.90% CI: [0.927, 1.001]
Primary
AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Granule Cohort
Time frame: Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The pharmacokinetic 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 pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Granule Cohort | 7749.8 ng*hr/mL | Standard Deviation 1188.8 |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | AUC(0-48): Area Under the Plasma Concentration-Time Curve From Time 0 to 48 Hours Postdose for TAK-536 in Granule Cohort | 7893.2 ng*hr/mL | Standard Deviation 1336.61 |
Comparison: Based on the ANOVA in which the natural logarithms of AUC(0-48) of TAK-536 were used as dependent variables, and formulation, sequence (administration order) and administration period were used as fixed effects, bioequivalence was assessed providing two-sided 90% CIs for the differences between the formulations and between the periods.90% CI: [0.958, 1.011]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-536 in Dry Syrup Cohort
Time frame: Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The pharmacokinetic 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 pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Cmax: Maximum Observed Plasma Concentration for TAK-536 in Dry Syrup Cohort | 886.1 nanogram per milliliter (ng/mL) | Standard Deviation 133.76 |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Cmax: Maximum Observed Plasma Concentration for TAK-536 in Dry Syrup Cohort | 976.7 nanogram per milliliter (ng/mL) | Standard Deviation 140.97 |
Comparison: Based on the ANOVA in which the natural logarithms of Cmax of TAK-536 were used as dependent variables, and formulation, sequence (administration order) and administration period were used as fixed effects, bioequivalence was assessed providing two-sided 90% CIs for the differences between the formulations and between the periods.90% CI: [0.88, 0.933]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-536 in Granule Cohort
Time frame: Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The pharmacokinetic 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 pharmacokinetics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Cmax: Maximum Observed Plasma Concentration for TAK-536 in Granule Cohort | 943.2 ng/mL | Standard Deviation 106.76 |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Cmax: Maximum Observed Plasma Concentration for TAK-536 in Granule Cohort | 973.7 ng/mL | Standard Deviation 178.75 |
Comparison: Based on the ANOVA in which the natural logarithms of Cmax of TAK-536 were used as dependent variables, and formulation, sequence (administration order) and administration period were used as fixed effects, bioequivalence was assessed providing two-sided 90% CIs for the differences between the formulations and between the periods.90% CI: [0.938, 1.022]
Secondary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 6 of Intervention Period 2
Population: The safety analysis set included all participants who received the study drug at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 5 participants |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 5 participants |
| Granule Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 0 participants |
| Granule Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | 3 participants |
Secondary
Number of Participants Who Had Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG)
Time frame: Baseline up to Day 6 of Intervention Period 2
Population: The safety analysis set included all participants who received the study drug at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants Who Had Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) | 0 participants |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants Who Had Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) | 0 participants |
| Granule Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants Who Had Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) | 0 participants |
| Granule Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants Who Had Clinically Meaningful Changes From Baseline in 12-lead Electrocardiograms (ECG) | 0 participants |
Secondary
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values
Time frame: Baseline up to Day 6 of Intervention Period 2
Population: The safety analysis set included all participants who received the study drug at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | 4 participants |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | 5 participants |
| Granule Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | 0 participants |
| Granule Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values | 2 participants |
Secondary
Number of Participants With TEAEs Related to Body Weight
Time frame: Baseline up to Day 6 of Intervention Period 2
Population: The safety analysis set included all participants who received the study drug at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Granule Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Granule Cohort: TAK-536 10 mg Commercial Formulation | 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 Day 6 of Intervention Period 2
Population: The safety analysis set included all participants who received the study drug at least once.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dry Syrup Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Dry Syrup Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants With TEAEs Related to Vital Signs | 1 participants |
| Granule Cohort: TAK-536 10 mg Pediatric Formulation | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Granule Cohort: TAK-536 10 mg Commercial Formulation | Number of Participants With TEAEs Related to Vital Signs | 0 participants |