Japanese Healthy Adult Male
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to evaluate the BE of single oral dose of TAK-438 OD 20 milligram (mg) tablet without water and TAK-438 20 mg tablet with water (Study 1), and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2) in Japanese healthy adult male participants.
Detailed description
The drug being tested in this study is called TAK-438 OD tablet. TAK-438 OD tablet is being tested in Japanese healthy adult men. This study will evaluate bioequivalence of single oral dose of TAK-438 OD 20 mg tablet without water and TAK-438 20 mg tablet with water (Study 1), and TAK-438 OD 20 mg tablet with water and TAK-438 20 mg tablet with water (Study 2). The study will enroll up to 144 participants in total (Study 1 + 2). In Study 1 and 2, participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups; Study 1: * TAK-438 OD 20 mg tablet without water (Period 1) + TAK-438 20 mg tablet with water (Period 2) * TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet without water (Period 2) Study 2: * TAK-438 OD 20 mg tablet with water (Period 1) + TAK-438 20 mg tablet with water (Period 2) * TAK-438 20 mg tablet with water (Period 1) + TAK-438 OD 20 mg tablet with water (Period 2) This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 11 days. Participants will make two visits to the clinic and be hospitalized for four days each in Periods 1 and 2.
Interventions
DRUGTAK-438 OD
TAK-438 OD tablet
DRUGTAK-438
TAK-438 tablet
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 60 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. 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, aged 20 to 60 years, inclusive, at the time of informed consent. 4. The participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) from 18.5 to 25.0 kilogram per square meter (kg/m\^2), inclusive at Screening. 5. The participant must be a current nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months prior to the start of study drug administration in Period 1. 6. The participant must be judged to be in good health by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead electrocardiogram (ECG), and vital sign measurements performed at the Screening Visit and prior to the start of study drug administration in Period 1.
Exclusion criteria
1. The participant has received any investigational compound within 16 weeks (112 days) prior to the start of study drug administration in Period 1. 2. The participant has received TAK-438 in a previous clinical study or as a therapeutic agent. 3. The participant is an immediate family member of or a study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress. 4. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, or endocrine disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate in the study or potentially confound its results. 5. The participant has hypersensitivity to any component of TAK-438 OD tablet or TAK-438 tablet. 6. The participant has a positive urine drug result for drugs of abuse at Screening. 7. The participant has a history of drug or 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. The participant has taken any excluded medication, supplements, or food products during the specified 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. 10. The participant has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1. 11. The participant has a positive test result for hepatitis B virus 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 milliliter (mL) within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the start of study drug administration in 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 drug administration in Period 1. 15. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of study drug administration in Period 1. 16. The participant has a Screening or Check-in (Day -1) ECG that was abnormal (clinically significant). 17. The participant has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limits of normal (ULN). 18. The participant 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 |
|---|---|
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| Cmax: Maximum Observed Plasma Concentration for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
Secondary
| Measure | Time frame |
|---|---|
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
| λz: Terminal Disposition Phase Rate Constant for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Japan from 30 January 2019 to 12 March 2019.
Pre-assignment details
Healthy Japanese male participants were enrolled in 1 of the 2 treatment sequences to receive TAK-438 OD 20 milligram (mg) or TAK-438 20 mg with or without water in Study 1, and TAK-438 OD 20 mg or TAK-438 20 mg with water in Study 2. Study was completed with Pilot study since results from interim analysis satisfied the criteria of bioequivalence.
Participants by arm
| Arm | Count |
|---|---|
| Pilot BE Study 1, Sequence A: TAK-438 OD 20 mg + TAK-438 20 mg TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 2. | 12 |
| Pilot BE Study 1, Sequence B: TAK-438 20 mg + TAK-438 OD 20 mg TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1 followed by a washout period of at least 7 days, further followed TAK-438 OD 20 mg, tablet, orally without water under fasted condition, once on Day 1 of Period 2. | 12 |
| Pilot BE Study 2, Sequence C: TAK-438 OD 20 mg + TAK-438 20 mg TAK-438 OD 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2. | 12 |
| Pilot BE Study 2, Sequence D: TAK-438 20 mg + TAK-438 OD 20 mg TAK-438 20 mg, tablet, orally with water under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 7 days, further followed by TAK-438 OD 20 mg tablet, orally with water under fasted condition, once on Day 1 of Period 2. | 12 |
| Total | 48 |
Baseline characteristics
| Characteristic | Total | Pilot BE Study 1, Sequence A: TAK-438 OD 20 mg + TAK-438 20 mg | Pilot BE Study 1, Sequence B: TAK-438 20 mg + TAK-438 OD 20 mg | Pilot BE Study 2, Sequence C: TAK-438 OD 20 mg + TAK-438 20 mg | Pilot BE Study 2, Sequence D: TAK-438 20 mg + TAK-438 OD 20 mg |
|---|---|---|---|---|---|
| Age, Continuous | 25.1 years STANDARD_DEVIATION 6.34 | 22.1 years STANDARD_DEVIATION 3.87 | 26.0 years STANDARD_DEVIATION 6.74 | 26.5 years STANDARD_DEVIATION 7.19 | 26.0 years STANDARD_DEVIATION 6.76 |
| Alcohol Consumption Drank a few times per month | 14 Participants | 6 Participants | 3 Participants | 4 Participants | 1 Participants |
| Alcohol Consumption Drank a few times per week | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Alcohol Consumption Never drank | 31 Participants | 6 Participants | 7 Participants | 8 Participants | 10 Participants |
| Body Mass Index (BMI) | 21.10 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.718 | 20.28 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.817 | 21.15 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.829 | 20.94 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.781 | 22.03 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.043 |
| Caffeine Consumption Had caffeine consumption | 11 Participants | 2 Participants | 1 Participants | 4 Participants | 4 Participants |
| Caffeine Consumption Had no caffeine consumption | 37 Participants | 10 Participants | 11 Participants | 8 Participants | 8 Participants |
| Height | 172.0 centimeter (cm) STANDARD_DEVIATION 5.59 | 171.8 centimeter (cm) STANDARD_DEVIATION 4 | 170.0 centimeter (cm) STANDARD_DEVIATION 6.52 | 173.9 centimeter (cm) STANDARD_DEVIATION 4.32 | 172.2 centimeter (cm) STANDARD_DEVIATION 6.94 |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — | — |
| Region of Enrollment Japan | 48 Participants | 12 Participants | 12 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 48 Participants | 12 Participants | 12 Participants | 12 Participants | 12 Participants |
| Smoking Classification Former smoker | 5 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Smoking Classification Never smoked | 43 Participants | 11 Participants | 11 Participants | 10 Participants | 11 Participants |
| Weight | 62.38 kilogram (kg) STANDARD_DEVIATION 5.586 | 59.83 kilogram (kg) STANDARD_DEVIATION 4.672 | 60.95 kilogram (kg) STANDARD_DEVIATION 4.72 | 63.29 kilogram (kg) STANDARD_DEVIATION 4.86 | 65.44 kilogram (kg) STANDARD_DEVIATION 6.716 |
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 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Population: The pharmacokinetic (PK) analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot BE Study 1: TAK-438 OD 20 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | 190.2 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 67.984 |
| Pilot BE Study 1: TAK-438 20 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | 194.3 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 67.693 |
| Pilot BE Study 2: TAK-438 OD 20 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | 201.6 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 81.799 |
| Pilot BE Study 2: TAK-438 20 mg | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Plasma Concentration for TAK-438 Free Base (TAK-438F) | 201.2 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 75.813 |
90% CI: [-0.0752, 0.0329]
90% CI: [-0.0778, 0.0815]
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot BE Study 1: TAK-438 OD 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-438F | 22.62 nanogram per milliliter (ng/mL) | Standard Deviation 7.8152 |
| Pilot BE Study 1: TAK-438 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-438F | 24.26 nanogram per milliliter (ng/mL) | Standard Deviation 8.0676 |
| Pilot BE Study 2: TAK-438 OD 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-438F | 21.85 nanogram per milliliter (ng/mL) | Standard Deviation 7.7286 |
| Pilot BE Study 2: TAK-438 20 mg | Cmax: Maximum Observed Plasma Concentration for TAK-438F | 23.70 nanogram per milliliter (ng/mL) | Standard Deviation 8.5998 |
90% CI: [-0.1404, 0.0008]
90% CI: [-0.1658, 0.0036]
Secondary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot BE Study 1: TAK-438 OD 20 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | 192.5 h*ng/mL | Standard Deviation 68.755 |
| Pilot BE Study 1: TAK-438 20 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | 196.4 h*ng/mL | Standard Deviation 68.436 |
| Pilot BE Study 2: TAK-438 OD 20 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | 204.3 h*ng/mL | Standard Deviation 83.014 |
| Pilot BE Study 2: TAK-438 20 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | 203.6 h*ng/mL | Standard Deviation 77.63 |
90% CI: [-0.0731, 0.0333]
90% CI: [-0.076, 0.083]
Secondary
MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot BE Study 1: TAK-438 OD 20 mg | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | 9.576 hour | Standard Deviation 1.1807 |
| Pilot BE Study 1: TAK-438 20 mg | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | 9.258 hour | Standard Deviation 0.91125 |
| Pilot BE Study 2: TAK-438 OD 20 mg | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | 9.831 hour | Standard Deviation 1.3506 |
| Pilot BE Study 2: TAK-438 20 mg | MRT∞,ev: Mean Residence Time After Extravascular Administration From Time 0 to Infinity for TAK-438F | 9.544 hour | Standard Deviation 1.4121 |
90% CI: [0.0022, 0.0599]
90% CI: [-0.0003, 0.0616]
Secondary
Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pilot BE Study 1: TAK-438 OD 20 mg | Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F | 2.000 hour |
| Pilot BE Study 1: TAK-438 20 mg | Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F | 1.750 hour |
| Pilot BE Study 2: TAK-438 OD 20 mg | Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F | 2.000 hour |
| Pilot BE Study 2: TAK-438 20 mg | Tmax: Time of First Occurrence of Maximum Plasma Concentration (Cmax) for TAK-438F | 2.000 hour |
90% CI: [0.0199, 0.3605]
90% CI: [0.0558, 0.3725]
Secondary
λz: Terminal Disposition Phase Rate Constant for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, and whose PK data were evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot BE Study 1: TAK-438 OD 20 mg | λz: Terminal Disposition Phase Rate Constant for TAK-438F | 0.1014 per hour (1/hour) | Standard Deviation 0.014441 |
| Pilot BE Study 1: TAK-438 20 mg | λz: Terminal Disposition Phase Rate Constant for TAK-438F | 0.09903 per hour (1/hour) | Standard Deviation 0.011269 |
| Pilot BE Study 2: TAK-438 OD 20 mg | λz: Terminal Disposition Phase Rate Constant for TAK-438F | 0.09807 per hour (1/hour) | Standard Deviation 0.013021 |
| Pilot BE Study 2: TAK-438 20 mg | λz: Terminal Disposition Phase Rate Constant for TAK-438F | 0.09989 per hour (1/hour) | Standard Deviation 0.01669 |
90% CI: [-0.0112, 0.053]
90% CI: [-0.0508, 0.0238]