Healthy Volunteers
Conditions
Keywords
Drug Therapy
Brief summary
The purposes of this study are to evaluate BE between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 milligram (mg) and aspirin enteric-coated tablet 100 mg in Japanese healthy adult men (Study 1), and to evaluate the effects of food on the pharmacokinetics of TAK-438ASA tablet in Japanese healthy adult men (Study 2).
Detailed description
The drug under investigation in this study is called TAK-438ASA. TAK-438ASA is being tested in Japanese healthy adult men. This study consists of two studies to evaluate bioequivalence (Study 1) and the effects of food (Study 2). Study 1 (split into a Pilot phase and a Pivotal phase) will look at bioequivalence between a single-dose of TAK-438ASA tablet versus a single-dose combination of TAK-438 tablet 10 mg and aspirin enteric-coated tablet 100 mg. Study 2 will look at the effects of food on the pharmacokinetics of TAK-438ASA tablet. The study will enroll up to 440 participants in total (Study 1 + 2). For Study 1, 12 participants per group (24 participants in total) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups for the pilot study to estimate the sample size of Pivotal study. After pilot study, 202 participants as a maximum per group (404 participants in total) will be randomly assigned to one of the two treatment groups: * TAK-438ASA tablet (Period 1) + TAK-438 10 mg tablet and Aspirin 100 mg tablet (Period 2) * TAK-438 10 mg tablet and Aspirin 100 mg tablet (Period 1) + TAK-438ASA tablet (Period 2) For Study 2, 6 participants per group (12 participants in total) will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups: * TAK-438ASA tablet (Fasted condition) + TAK-438ASA tablet (Fed condition) * TAK-438ASA tablet (Fed condition) + TAK-438ASA tablet (Fasted condition) This single-center trial will be conducted in Japan. The overall time to participate in this study is approximately 18 days. Participants will make two visits to the clinic and be hospitalized for eight days in total.
Interventions
DRUGAspirin
Aspirin enteric-coated tablet.
DRUGTAK-438ASA
TAK-438ASA 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, participants are capable of understanding the procedures required for the study and complying with its requirements. 2. Participants sign and date an informed consent form by themselves prior to the initiation of any study procedures. 3. Japanese healthy men aged greater than or equal to (\>=) 20 and less than or equal to (=\<) 60, inclusive, at the time of consent. 4. Body weight \>=50 kilogram (kg) as well as body mass index (BMI) \>=18.5 kilogram per meter square (kg/m\^2) and =\<25.0 kg/m\^2 at screening test.
Exclusion criteria
1. Participants who received study drug within 16 weeks (112 days) prior to the start of study treatment in Period 1. 2. Participants who received TAK-438 or aspirin in a previous study. 3. Staffs at the study site and their family, or participants who depend on the study-related staffs at the study site (example, husband and wife, parents, children, brothers and sisters), or participants who may be constrained to consent to the study. 4. Participants with uncontrolled and clinically significant neurological, cardiovascular, lung, hepatic, renal, metabolic, gastrointestinal, urinary or endocrine disease, or other abnormalities (except for diseases investigated) that might affect the study participation or impact the results of the study. 5. Participants with a previous or current history of aspirin asthma (asthmatic attack induced by non-steroidal anti-inflammatory drugs, etc.). 6. Participants with hypersensitivity for components of TAK-438 tablet or aspirin enteric-coated tablet, or salicylic acid-based products. 7. Positive result in urinary test for illegal drug abuse at screening. 8. Participants who have a history of illegal drug abuse or alcoholism within the past 2 years prior to the screening visit, or who are not willing to refrain from alcohol consumption and drug use during the study period. 9. Participants who ingested a medicine, a supplement or food forbidden to be used in combination during the specified time period. 10. Participants with a current history or recent episodes (within the past 6 months) of gastrointestinal diseases (malabsorption, gastroesophageal reflux, peptic ulcer disease, erosive oesophagitis), frequent (at least once per week) heartburn or surgical intervention that might affect drug absorption. 11. Participants with a history of cancer, except for basal cell carcinoma in remission for \>=5 years prior to Day 1. 12. Positive results at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological test for syphilis. 13. Participants who have difficulties in blood draw from peripheral veins. 14. Participants who had \>=200 milliliter (mL) of whole blood drawn within 4 weeks (28 days) prior to the start of study treatment in Period 1 or who had \>=400 mL of whole blood drawn within 12 weeks (84 days) prior to the start of study treatment in Period 1. 15. Participants who had a total of \>=800 mL of whole blood drawn within 52 weeks (364 days) prior to the start of study treatment in Period 1. 16. Participants who had blood components drawn within 2 weeks (14 days) prior to the start of study treatment in Period 1. 17. Clinically significant abnormalities in electrocardiogram at screening or admission (Day -1). 18. Participants with abnormal laboratory parameters suggestive of clinically significant underlying diseases or who have abnormal values in the following measures at screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) over the upper limit of normal. 19. Participants who are unlikely to comply with the protocol or deemed ineligible due to other reasons by the principal investigator or other investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
Secondary
| Measure | Time frame |
|---|---|
| Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose |
| Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 1, 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) post-dose |
| Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
| Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
| Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F | Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Japan from 8 March 2018 to 12 October 2018.
Pre-assignment details
Healthy male participants were enrolled in this 2-period cross-over design study to receive 1 of the 2 treatment sequences: fixed dose combination (FDC) of TAK-438 and aspirin (TAK-438ASA) or a free combination of TAK-438 and aspirin in Study 1, and to receive 1 of the 2 sequences: FDC of TAK-438ASA under fasted or fed conditions in Study 2.
Participants by arm
| Arm | Count |
|---|---|
| Pilot Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin TAK-438 10 milligram (mg) and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 2. | 12 |
| Pilot Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. | 12 |
| Pivotal Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 2. | 120 |
| Pivotal Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. | 120 |
| Study 2, Sequence C: TAK-438ASA (Fasted + Fed Condition) TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of Period 2. | 6 |
| Study 2, Sequence D: TAK-438ASA (Fed + Fasted Condition) TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of Period 1, followed by a washout period of at least 14 days, further followed by TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of Period 2. | 6 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 2 (1 Day) | Adverse Event | 1 | 0 | 0 | 1 | 0 | 0 |
| Washout Period (at Least 14 Days) | Withdrawal by Subject | 0 | 0 | 1 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Pilot Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin | Total | Study 2, Sequence D: TAK-438ASA (Fed + Fasted Condition) | Study 2, Sequence C: TAK-438ASA (Fasted + Fed Condition) | Pivotal Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA | Pivotal Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin | Pilot Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA |
|---|---|---|---|---|---|---|---|
| Age, Customized Between 20 and 60 years | 12 Participants | 276 Participants | 6 Participants | 6 Participants | 120 Participants | 120 Participants | 12 Participants |
| Age, Customized Greater than (>) 60 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Less than (<) 20 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Consumption of alcohol Drank a few times per month | 3 Participants | 154 Participants | 3 Participants | 3 Participants | 68 Participants | 72 Participants | 5 Participants |
| Consumption of alcohol Drank a few times per week | 2 Participants | 22 Participants | 0 Participants | 0 Participants | 9 Participants | 9 Participants | 2 Participants |
| Consumption of alcohol Drank daily | 2 Participants | 6 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants |
| Consumption of alcohol Never drank | 5 Participants | 94 Participants | 3 Participants | 3 Participants | 40 Participants | 38 Participants | 5 Participants |
| Consumption of caffeine Had caffeine consumption | 6 Participants | 55 Participants | 1 Participants | 2 Participants | 18 Participants | 23 Participants | 5 Participants |
| Consumption of caffeine Had no caffeine consumption | 6 Participants | 221 Participants | 5 Participants | 4 Participants | 102 Participants | 97 Participants | 7 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — | — | — | — | — |
| Region of Enrollment Japan | 12 Participants | 276 Participants | 6 Participants | 6 Participants | 120 Participants | 120 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 276 Participants | 6 Participants | 6 Participants | 120 Participants | 120 Participants | 12 Participants |
| Smoking classification Current smoker | 2 Participants | 25 Participants | 1 Participants | 1 Participants | 12 Participants | 9 Participants | 0 Participants |
| Smoking classification Ex-smoker | 3 Participants | 73 Participants | 1 Participants | 1 Participants | 32 Participants | 30 Participants | 6 Participants |
| Smoking classification Never smoked | 7 Participants | 178 Participants | 4 Participants | 4 Participants | 76 Participants | 81 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 23 | 0 / 237 | 0 / 239 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 24 | 0 / 23 | 8 / 237 | 3 / 239 | 1 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 0 / 237 | 0 / 239 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The pharmacokinetic (PK) analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F) | 92.46 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 32.128 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438F) | 91.95 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 31.431 |
90% CI: [-0.034, 0.0458]
Primary
Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin
Time frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | 873.5 h*ng/mL | Standard Deviation 220.94 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | 831.9 h*ng/mL | Standard Deviation 350.69 |
| Pivotal Study 1: TAK-438ASA | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | 912.3 h*ng/mL | Standard Deviation 327.58 |
| Pivotal Study 1: TAK-438 and Aspirin | Study 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin | 832.7 h*ng/mL | Standard Deviation 323.46 |
90% CI: [-0.0941, 0.2034]
90% CI: [0.0399, 0.1424]
Primary
Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F | 13.87 nanogram per milliliter (ng/mL) | Standard Deviation 5.0945 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F | 13.22 nanogram per milliliter (ng/mL) | Standard Deviation 5.0778 |
90% CI: [-0.0079, 0.1096]
Primary
Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin
Time frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | 647.6 ng/mL | Standard Deviation 326.77 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | 597.5 ng/mL | Standard Deviation 507.9 |
| Pivotal Study 1: TAK-438ASA | Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | 701.8 ng/mL | Standard Deviation 349.18 |
| Pivotal Study 1: TAK-438 and Aspirin | Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin | 558.0 ng/mL | Standard Deviation 404.26 |
90% CI: [-0.133, 0.3162]
90% CI: [0.1519, 0.3068]
Secondary
Study 1, 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) post-dose
Population: The PK analysis set included all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | 94.71 h*ng/mL | Standard Deviation 32.334 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F | 93.78 h*ng/mL | Standard Deviation 31.828 |
90% CI: [-0.0299, 0.05]
Secondary
Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin
Time frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | 876.5 h*ng/mL | Standard Deviation 221.1 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | 834.6 h*ng/mL | Standard Deviation 349.28 |
| Pivotal Study 1: TAK-438ASA | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | 915.8 h*ng/mL | Standard Deviation 328.82 |
| Pivotal Study 1: TAK-438 and Aspirin | Study 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin | 855.4 h*ng/mL | Standard Deviation 322.27 |
90% CI: [-0.0937, 0.2032]
90% CI: [0.0141, 0.1167]
Secondary
Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F | 0.08565 1 per hour | Standard Deviation 0.009023 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F | 0.08788 1 per hour | Standard Deviation 0.013025 |
90% CI: [-0.0676, 0.0286]
Secondary
Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin
Time frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | 1.734 1 per hour | Standard Deviation 0.30398 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | 1.703 1 per hour | Standard Deviation 0.30765 |
| Pivotal Study 1: TAK-438ASA | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | 1.754 1 per hour | Standard Deviation 0.32224 |
| Pivotal Study 1: TAK-438 and Aspirin | Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin | 1.795 1 per hour | Standard Deviation 0.35228 |
90% CI: [-0.0734, 0.103]
90% CI: [-0.0463, 0.0424]
Secondary
Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F | 9.610 hour | Standard Deviation 1.244 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F | 9.751 hour | Standard Deviation 1.3853 |
90% CI: [-0.0448, 0.0149]
Secondary
Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin
Time frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | 4.629 hour | Standard Deviation 1.4634 |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | 5.194 hour | Standard Deviation 1.5154 |
| Pivotal Study 1: TAK-438ASA | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | 4.398 hour | Standard Deviation 1.0552 |
| Pivotal Study 1: TAK-438 and Aspirin | Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin | 5.152 hour | Standard Deviation 2.0334 |
90% CI: [-0.2179, -0.0206]
90% CI: [-0.173, -0.1002]
Secondary
Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Samples were not collected for Pivotal Study 1 because sufficient results were available for TAK-438F from the Pilot Study 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F | 1.500 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F | 1.500 hour |
90% CI: [-0.1662, 0.11]
Secondary
Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin
Time frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | 4.000 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | 4.500 hour |
| Pivotal Study 1: TAK-438ASA | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | 4.000 hour |
| Pivotal Study 1: TAK-438 and Aspirin | Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin | 4.500 hour |
90% CI: [-0.2478, -0.0443]
90% CI: [-0.2084, -0.1264]
Secondary
Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Unchanged aspirin | 481.3 mcg | Standard Deviation 173.04 |
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicylic acid | 2318 mcg | Standard Deviation 1904.7 |
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicyluric acid | 80180 mcg | Standard Deviation 9852.2 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Unchanged aspirin | 817.3 mcg | Standard Deviation 403.78 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicylic acid | 2076 mcg | Standard Deviation 1159.4 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-24): Amount of Drug Excreted in Urine From Time 0 to 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicyluric acid | 83800 mcg | Standard Deviation 4019.7 |
Secondary
Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-I | 150.1 microgram (mcg) | Standard Deviation 99.765 |
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-III | 0.000 microgram (mcg) | Standard Deviation 0 |
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | TAK-438F | 433.3 microgram (mcg) | Standard Deviation 63.305 |
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-IV-Sul | 237.0 microgram (mcg) | Standard Deviation 56.783 |
| Pilot Study 1: TAK-438ASA | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-II | 0.000 microgram (mcg) | Standard Deviation 0 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-IV-Sul | 196.8 microgram (mcg) | Standard Deviation 59.876 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-II | 0.000 microgram (mcg) | Standard Deviation 0 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | TAK-438F | 583.1 microgram (mcg) | Standard Deviation 110.83 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-III | 0.000 microgram (mcg) | Standard Deviation 0 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Ae(0-48): Amount of Drug Excreted in Urine From Time 0 to 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-I | 153.4 microgram (mcg) | Standard Deviation 61.628 |
Secondary
Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 816.7 h*ng/mL | Standard Deviation 295.55 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 20070 h*ng/mL | Standard Deviation 5318.8 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 1007 h*ng/mL | Standard Deviation 222.08 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 20340 h*ng/mL | Standard Deviation 5119.5 |
90% CI: [-0.0048, 0.4246]
90% CI: [-0.0712, 0.0986]
Secondary
Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 272.1 h*ng/mL | Standard Deviation 49.341 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 82.96 h*ng/mL | Standard Deviation 14.931 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 30.80 h*ng/mL | Standard Deviation 14.808 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 111.5 h*ng/mL | Standard Deviation 38.376 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 82.89 h*ng/mL | Standard Deviation 16.467 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 93.20 h*ng/mL | Standard Deviation 41.338 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 102.9 h*ng/mL | Standard Deviation 18.851 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 251.9 h*ng/mL | Standard Deviation 44.461 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 24.17 h*ng/mL | Standard Deviation 12.927 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve From Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 79.69 h*ng/mL | Standard Deviation 22.117 |
90% CI: [0.1652, 0.2671]
Secondary
Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-I | 290.4 h*ng/mL | Standard Deviation 50.706 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-III | 83.59 h*ng/mL | Standard Deviation 15.202 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-II | 50.77 h*ng/mL | Standard Deviation 19.175 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 115.9 h*ng/mL | Standard Deviation 37.933 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 84.26 h*ng/mL | Standard Deviation 16.89 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 97.60 h*ng/mL | Standard Deviation 40.882 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 104.3 h*ng/mL | Standard Deviation 19.47 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-I | 266.9 h*ng/mL | Standard Deviation 44.125 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-II | 58.29 h*ng/mL | Standard Deviation 63.088 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-438F and Its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul) | M-III | 80.25 h*ng/mL | Standard Deviation 22.318 |
90% CI: [0.1609, 0.2667]
Secondary
Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 817.9 h*ng/mL | Standard Deviation 296.13 |
| Pilot Study 1: TAK-438ASA | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 20010 h*ng/mL | Standard Deviation 5299.3 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 1008 h*ng/mL | Standard Deviation 221.75 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 20290 h*ng/mL | Standard Deviation 5048.4 |
90% CI: [-0.0061, 0.4239]
90% CI: [-0.0639, 0.0918]
Secondary
Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 258.6 h*ng/mL | Standard Deviation 49.384 |
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 81.92 h*ng/mL | Standard Deviation 15.032 |
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 26.86 h*ng/mL | Standard Deviation 12.921 |
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 108.4 h*ng/mL | Standard Deviation 36.884 |
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 82.23 h*ng/mL | Standard Deviation 16.775 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 89.48 h*ng/mL | Standard Deviation 39.843 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 102.4 h*ng/mL | Standard Deviation 19.138 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 239.5 h*ng/mL | Standard Deviation 44.95 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 20.66 h*ng/mL | Standard Deviation 10.882 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 78.69 h*ng/mL | Standard Deviation 21.959 |
90% CI: [0.1675, 0.2706]
Secondary
Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 816.5 h*ng/mL | Standard Deviation 295.68 |
| Pilot Study 1: TAK-438ASA | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 19370 h*ng/mL | Standard Deviation 5108.5 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 1007 h*ng/mL | Standard Deviation 222.45 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 19760 h*ng/mL | Standard Deviation 4853.5 |
90% CI: [-0.0054, 0.4246]
90% CI: [-0.069, 0.1092]
Secondary
Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-I | 0.5577 liter per hour (l/h) | Standard Deviation 0.38695 |
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-III | 0.000 liter per hour (l/h) | Standard Deviation 0 |
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-II | 0.000 liter per hour (l/h) | Standard Deviation 0 |
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-IV-Sul | 2.148 liter per hour (l/h) | Standard Deviation 0.59016 |
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | TAK-438F | 5.213 liter per hour (l/h) | Standard Deviation 0.6576 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-IV-Sul | 2.126 liter per hour (l/h) | Standard Deviation 0.66434 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | TAK-438F | 5.604 liter per hour (l/h) | Standard Deviation 0.55389 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-I | 0.6018 liter per hour (l/h) | Standard Deviation 0.21705 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-II | 0.000 liter per hour (l/h) | Standard Deviation 0 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for TAK-438F and Its Metabolites (M-I, M-II, M-III, and M-IV-Sul) | M-III | 0.000 liter per hour (l/h) | Standard Deviation 0 |
Secondary
Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. Data for CLR of Salicyluric acid was not calculated since the plasma concentration of Salicyluric acid was not measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Unchanged aspirin | 0.6181 l/h | Standard Deviation 0.28917 |
| Pilot Study 1: TAK-438ASA | Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicylic acid | 0.1135 l/h | Standard Deviation 0.083534 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Unchanged aspirin | 0.7818 l/h | Standard Deviation 0.29682 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, CLR: Renal Clearance for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicylic acid | 0.1022 l/h | Standard Deviation 0.055826 |
Secondary
Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 41.26 ng/mL | Standard Deviation 9.0261 |
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 15.38 ng/mL | Standard Deviation 2.7078 |
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 2.820 ng/mL | Standard Deviation 0.83815 |
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 28.52 ng/mL | Standard Deviation 7.8634 |
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 12.73 ng/mL | Standard Deviation 2.5465 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 23.09 ng/mL | Standard Deviation 7.4466 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 18.35 ng/mL | Standard Deviation 5.4137 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 35.22 ng/mL | Standard Deviation 9.6886 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 2.131 ng/mL | Standard Deviation 0.57491 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 14.90 ng/mL | Standard Deviation 2.2273 |
90% CI: [0.218, 0.5126]
Secondary
Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set included all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 632.5 ng/mL | Standard Deviation 286.18 |
| Pilot Study 1: TAK-438ASA | Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 4414 ng/mL | Standard Deviation 930.76 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 949.0 ng/mL | Standard Deviation 415.75 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 5374 ng/mL | Standard Deviation 1119.4 |
90% CI: [0.0803, 0.7312]
90% CI: [0.1065, 0.2873]
Secondary
Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Unchanged aspirin | 0.4813 percentage of dose | Standard Deviation 0.17304 |
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicylic acid | 3.025 percentage of dose | Standard Deviation 2.4834 |
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicyluric acid | 74.02 percentage of dose | Standard Deviation 9.0984 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Unchanged aspirin | 0.8173 percentage of dose | Standard Deviation 0.40378 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicylic acid | 2.708 percentage of dose | Standard Deviation 1.5127 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-24): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 24 Hours for Unchanged Aspirin and Its Metabolites (Salicylic Acid and Salicyluric Acid) | Salicyluric acid | 77.34 percentage of dose | Standard Deviation 3.7218 |
Secondary
Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 1.499 percentage of dose | Standard Deviation 0.99551 |
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 0.000 percentage of dose | Standard Deviation 0 |
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 0.000 percentage of dose | Standard Deviation 0 |
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 1.854 percentage of dose | Standard Deviation 0.44353 |
| Pilot Study 1: TAK-438ASA | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 4.333 percentage of dose | Standard Deviation 0.63305 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 1.539 percentage of dose | Standard Deviation 0.46709 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 5.831 percentage of dose | Standard Deviation 1.1083 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 1.529 percentage of dose | Standard Deviation 0.61494 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 0.000 percentage of dose | Standard Deviation 0 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Fe(0-48): Fraction of Administered Dose Excreted Into Urine From Time 0 to Time 48 Hours for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 0.000 percentage of dose | Standard Deviation 0 |
Secondary
Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 9.653 hour | Standard Deviation 1.3591 |
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 6.797 hour | Standard Deviation 2.1059 |
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 12.92 hour | Standard Deviation 10.029 |
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 4.067 hour | Standard Deviation 1.4194 |
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 8.293 hour | Standard Deviation 1.1254 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 4.543 hour | Standard Deviation 1.6209 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 7.951 hour | Standard Deviation 0.82489 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 9.153 hour | Standard Deviation 1.0688 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 27.52 hour | Standard Deviation 38.721 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 6.826 hour | Standard Deviation 1.5924 |
Secondary
Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 0.3749 hour | Standard Deviation 0.042784 |
| Pilot Study 1: TAK-438ASA | Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 2.050 hour | Standard Deviation 0.32982 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 0.4373 hour | Standard Deviation 0.10311 |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 1.901 hour | Standard Deviation 0.26555 |
Secondary
Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 1.500 hour |
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 1.750 hour |
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 4.000 hour |
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 1.500 hour |
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 1.500 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-IV-Sul | 2.000 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | TAK-438F | 1.500 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-I | 1.500 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-II | 4.000 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and Its Metabolites (M-I, M-II, M-III and M-IV-Sul) | M-III | 2.000 hour |
Secondary
Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Time frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose
Population: The PK analysis set was defined as all participants who received at least one dose of study drug, who had no major protocol deviation, and whose PK data were evaluable.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 4.500 hour |
| Pilot Study 1: TAK-438ASA | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 5.500 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Unchanged aspirin | 4.000 hour |
| Pilot Study 1: TAK-438 and Aspirin | Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid) | Salicylic acid | 4.500 hour |