Trial Outcomes & Findings for A Study to Evaluate the Bioequivalence (BE) and the Food Effect of TAK-438ASA Tablet (NCT NCT03456960)
NCT ID: NCT03456960
Last Updated: 2019-11-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
276 participants
Primary outcome timeframe
Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose
Results posted on
2019-11-19
Participant Flow
Participants took part in the study at 1 investigative site in Japan from 8 March 2018 to 12 October 2018.
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Period 1 (1 Day)
STARTED
|
12
|
12
|
120
|
120
|
6
|
6
|
|
Period 1 (1 Day)
COMPLETED
|
12
|
12
|
120
|
120
|
6
|
6
|
|
Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period (at Least 14 Days)
STARTED
|
12
|
12
|
120
|
120
|
6
|
6
|
|
Washout Period (at Least 14 Days)
COMPLETED
|
12
|
12
|
119
|
118
|
6
|
6
|
|
Washout Period (at Least 14 Days)
NOT COMPLETED
|
0
|
0
|
1
|
2
|
0
|
0
|
|
Period 2 (1 Day)
STARTED
|
12
|
12
|
119
|
118
|
6
|
6
|
|
Period 2 (1 Day)
COMPLETED
|
11
|
12
|
119
|
117
|
6
|
6
|
|
Period 2 (1 Day)
NOT COMPLETED
|
1
|
0
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Washout Period (at Least 14 Days)
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
0
|
0
|
|
Period 2 (1 Day)
Adverse Event
|
1
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Pilot Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin
n=12 Participants
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.
|
Pilot Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA
n=12 Participants
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.
|
Pivotal Study 1, Sequence A: TAK-438ASA + TAK-438 and Aspirin
n=120 Participants
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.
|
Pivotal Study 1, Sequence B: TAK-438 and Aspirin + TAK-438ASA
n=120 Participants
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.
|
Study 2, Sequence C: TAK-438ASA (Fasted + Fed Condition)
n=6 Participants
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.
|
Study 2, Sequence D: TAK-438ASA (Fed + Fasted Condition)
n=6 Participants
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.
|
Total
n=276 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Customized
Less than (<) 20 years
|
0 Participants
n=12 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=120 Participants
|
0 Participants
n=120 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=276 Participants
|
|
Age, Customized
Between 20 and 60 years
|
12 Participants
n=12 Participants
|
12 Participants
n=12 Participants
|
120 Participants
n=120 Participants
|
120 Participants
n=120 Participants
|
6 Participants
n=6 Participants
|
6 Participants
n=6 Participants
|
276 Participants
n=276 Participants
|
|
Age, Customized
Greater than (>) 60 years
|
0 Participants
n=12 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=120 Participants
|
0 Participants
n=120 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=276 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=12 Participants
|
0 Participants
n=12 Participants
|
0 Participants
n=120 Participants
|
0 Participants
n=120 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=276 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=12 Participants
|
12 Participants
n=12 Participants
|
120 Participants
n=120 Participants
|
120 Participants
n=120 Participants
|
6 Participants
n=6 Participants
|
6 Participants
n=6 Participants
|
276 Participants
n=276 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Japan
|
12 Participants
n=12 Participants
|
12 Participants
n=12 Participants
|
120 Participants
n=120 Participants
|
120 Participants
n=120 Participants
|
6 Participants
n=6 Participants
|
6 Participants
n=6 Participants
|
276 Participants
n=276 Participants
|
|
Consumption of caffeine
Had caffeine consumption
|
6 Participants
n=12 Participants
|
5 Participants
n=12 Participants
|
23 Participants
n=120 Participants
|
18 Participants
n=120 Participants
|
2 Participants
n=6 Participants
|
1 Participants
n=6 Participants
|
55 Participants
n=276 Participants
|
|
Consumption of caffeine
Had no caffeine consumption
|
6 Participants
n=12 Participants
|
7 Participants
n=12 Participants
|
97 Participants
n=120 Participants
|
102 Participants
n=120 Participants
|
4 Participants
n=6 Participants
|
5 Participants
n=6 Participants
|
221 Participants
n=276 Participants
|
|
Consumption of alcohol
Drank daily
|
2 Participants
n=12 Participants
|
0 Participants
n=12 Participants
|
1 Participants
n=120 Participants
|
3 Participants
n=120 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
6 Participants
n=276 Participants
|
|
Consumption of alcohol
Drank a few times per week
|
2 Participants
n=12 Participants
|
2 Participants
n=12 Participants
|
9 Participants
n=120 Participants
|
9 Participants
n=120 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
22 Participants
n=276 Participants
|
|
Consumption of alcohol
Drank a few times per month
|
3 Participants
n=12 Participants
|
5 Participants
n=12 Participants
|
72 Participants
n=120 Participants
|
68 Participants
n=120 Participants
|
3 Participants
n=6 Participants
|
3 Participants
n=6 Participants
|
154 Participants
n=276 Participants
|
|
Consumption of alcohol
Never drank
|
5 Participants
n=12 Participants
|
5 Participants
n=12 Participants
|
38 Participants
n=120 Participants
|
40 Participants
n=120 Participants
|
3 Participants
n=6 Participants
|
3 Participants
n=6 Participants
|
94 Participants
n=276 Participants
|
|
Smoking classification
Never smoked
|
7 Participants
n=12 Participants
|
6 Participants
n=12 Participants
|
81 Participants
n=120 Participants
|
76 Participants
n=120 Participants
|
4 Participants
n=6 Participants
|
4 Participants
n=6 Participants
|
178 Participants
n=276 Participants
|
|
Smoking classification
Current smoker
|
2 Participants
n=12 Participants
|
0 Participants
n=12 Participants
|
9 Participants
n=120 Participants
|
12 Participants
n=120 Participants
|
1 Participants
n=6 Participants
|
1 Participants
n=6 Participants
|
25 Participants
n=276 Participants
|
|
Smoking classification
Ex-smoker
|
3 Participants
n=12 Participants
|
6 Participants
n=12 Participants
|
30 Participants
n=120 Participants
|
32 Participants
n=120 Participants
|
1 Participants
n=6 Participants
|
1 Participants
n=6 Participants
|
73 Participants
n=276 Participants
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
91.95 hour*nanogram per milliliter (h*ng/mL)
Standard Deviation 31.431
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F
|
13.87 nanogram per milliliter (ng/mL)
Standard Deviation 5.0945
|
13.22 nanogram per milliliter (ng/mL)
Standard Deviation 5.0778
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=233 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=233 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
831.9 h*ng/mL
Standard Deviation 350.69
|
912.3 h*ng/mL
Standard Deviation 327.58
|
832.7 h*ng/mL
Standard Deviation 323.46
|
PRIMARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=233 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=233 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin
|
647.6 ng/mL
Standard Deviation 326.77
|
597.5 ng/mL
Standard Deviation 507.90
|
701.8 ng/mL
Standard Deviation 349.18
|
558.0 ng/mL
Standard Deviation 404.26
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
93.78 h*ng/mL
Standard Deviation 31.828
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F
|
1.500 hour
Interval 1.0 to 3.0
|
1.500 hour
Interval 1.0 to 3.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for TAK-438F
|
9.610 hour
Standard Deviation 1.2440
|
9.751 hour
Standard Deviation 1.3853
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F
|
0.08565 1 per hour
Standard Deviation 0.0090230
|
0.08788 1 per hour
Standard Deviation 0.013025
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=231 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=221 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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 221.10
|
834.6 h*ng/mL
Standard Deviation 349.28
|
915.8 h*ng/mL
Standard Deviation 328.82
|
855.4 h*ng/mL
Standard Deviation 322.27
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=233 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=233 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin
|
4.000 hour
Interval 2.5 to 8.5
|
4.500 hour
Interval 3.0 to 8.5
|
4.000 hour
Interval 2.0 to 11.0
|
4.500 hour
Interval 1.0 to 12.0
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=231 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=221 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, MRT (Infinity,ev): Mean Residence Time From Time 0 to Infinity for Unchanged Aspirin
|
4.629 hour
Standard Deviation 1.4634
|
5.194 hour
Standard Deviation 1.5154
|
4.398 hour
Standard Deviation 1.0552
|
5.152 hour
Standard Deviation 2.0334
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=23 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=231 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=221 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin
|
1.734 1 per hour
Standard Deviation 0.30398
|
1.703 1 per hour
Standard Deviation 0.30765
|
1.754 1 per hour
Standard Deviation 0.32224
|
1.795 1 per hour
Standard Deviation 0.35228
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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 16.890
|
104.3 h*ng/mL
Standard Deviation 19.470
|
—
|
—
|
|
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
|
266.9 h*ng/mL
Standard Deviation 44.125
|
—
|
—
|
|
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
|
58.29 h*ng/mL
Standard Deviation 63.088
|
—
|
—
|
|
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
|
80.25 h*ng/mL
Standard Deviation 22.318
|
—
|
—
|
|
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
|
97.60 h*ng/mL
Standard Deviation 40.882
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
102.9 h*ng/mL
Standard Deviation 18.851
|
—
|
—
|
|
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
|
251.9 h*ng/mL
Standard Deviation 44.461
|
—
|
—
|
|
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
|
24.17 h*ng/mL
Standard Deviation 12.927
|
—
|
—
|
|
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
|
79.69 h*ng/mL
Standard Deviation 22.117
|
—
|
—
|
|
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
|
93.20 h*ng/mL
Standard Deviation 41.338
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
102.4 h*ng/mL
Standard Deviation 19.138
|
—
|
—
|
|
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
|
239.5 h*ng/mL
Standard Deviation 44.950
|
—
|
—
|
|
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
|
20.66 h*ng/mL
Standard Deviation 10.882
|
—
|
—
|
|
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
|
78.69 h*ng/mL
Standard Deviation 21.959
|
—
|
—
|
|
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
|
89.48 h*ng/mL
Standard Deviation 39.843
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
35.22 ng/mL
Standard Deviation 9.6886
|
—
|
—
|
|
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
|
2.131 ng/mL
Standard Deviation 0.57491
|
—
|
—
|
|
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
|
18.35 ng/mL
Standard Deviation 5.4137
|
—
|
—
|
|
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
|
14.90 ng/mL
Standard Deviation 2.2273
|
—
|
—
|
|
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
|
23.09 ng/mL
Standard Deviation 7.4466
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
Interval 1.0 to 2.0
|
1.500 hour
Interval 1.0 to 3.0
|
—
|
—
|
|
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
Interval 1.0 to 1.5
|
1.500 hour
Interval 1.0 to 4.0
|
—
|
—
|
|
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
Interval 3.0 to 4.0
|
4.000 hour
Interval 4.0 to 10.0
|
—
|
—
|
|
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
Interval 1.0 to 2.0
|
2.000 hour
Interval 1.0 to 4.0
|
—
|
—
|
|
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
Interval 1.0 to 3.0
|
2.000 hour
Interval 1.5 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
7.951 hour
Standard Deviation 0.82489
|
—
|
—
|
|
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
|
9.153 hour
Standard Deviation 1.0688
|
—
|
—
|
|
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
|
27.52 hour
Standard Deviation 38.721
|
—
|
—
|
|
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
|
6.826 hour
Standard Deviation 1.5924
|
—
|
—
|
|
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
|
4.543 hour
Standard Deviation 1.6209
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
1008 h*ng/mL
Standard Deviation 221.75
|
—
|
—
|
|
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
|
20290 h*ng/mL
Standard Deviation 5048.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
20340 h*ng/mL
Standard Deviation 5119.5
|
—
|
—
|
|
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
|
1007 h*ng/mL
Standard Deviation 222.08
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
1007 h*ng/mL
Standard Deviation 222.45
|
—
|
—
|
|
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
|
19760 h*ng/mL
Standard Deviation 4853.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
949.0 ng/mL
Standard Deviation 415.75
|
—
|
—
|
|
Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Salicylic acid
|
4414 ng/mL
Standard Deviation 930.76
|
5374 ng/mL
Standard Deviation 1119.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Salicylic acid
|
5.500 hour
Interval 3.5 to 6.5
|
4.500 hour
Interval 3.0 to 8.0
|
—
|
—
|
|
Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and Its Metabolite (Salicylic Acid)
Unchanged aspirin
|
4.500 hour
Interval 2.0 to 6.0
|
4.000 hour
Interval 2.5 to 7.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
0.4373 hour
Standard Deviation 0.10311
|
—
|
—
|
|
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
|
1.901 hour
Standard Deviation 0.26555
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
583.1 microgram (mcg)
Standard Deviation 110.83
|
—
|
—
|
|
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 0.0000
|
0.000 microgram (mcg)
Standard Deviation 0.0000
|
—
|
—
|
|
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 0.0000
|
0.000 microgram (mcg)
Standard Deviation 0.0000
|
—
|
—
|
|
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
|
153.4 microgram (mcg)
Standard Deviation 61.628
|
—
|
—
|
|
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
|
196.8 microgram (mcg)
Standard Deviation 59.876
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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 0.0000
|
0.000 percentage of dose
Standard Deviation 0.0000
|
—
|
—
|
|
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 0.0000
|
0.000 percentage of dose
Standard Deviation 0.0000
|
—
|
—
|
|
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
|
1.539 percentage of dose
Standard Deviation 0.46709
|
—
|
—
|
|
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
|
5.831 percentage of dose
Standard Deviation 1.1083
|
—
|
—
|
|
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
|
1.529 percentage of dose
Standard Deviation 0.61494
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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 0.65760
|
5.604 liter per hour (l/h)
Standard Deviation 0.55389
|
—
|
—
|
|
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
|
0.6018 liter per hour (l/h)
Standard Deviation 0.21705
|
—
|
—
|
|
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 0.0000
|
0.000 liter per hour (l/h)
Standard Deviation 0.0000
|
—
|
—
|
|
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 0.0000
|
0.000 liter per hour (l/h)
Standard Deviation 0.0000
|
—
|
—
|
|
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
|
2.126 liter per hour (l/h)
Standard Deviation 0.66434
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
817.3 mcg
Standard Deviation 403.78
|
—
|
—
|
|
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
|
2076 mcg
Standard Deviation 1159.4
|
—
|
—
|
|
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
|
83800 mcg
Standard Deviation 4019.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
0.8173 percentage of dose
Standard Deviation 0.40378
|
—
|
—
|
|
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
|
2.708 percentage of dose
Standard Deviation 1.5127
|
—
|
—
|
|
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
|
77.34 percentage of dose
Standard Deviation 3.7218
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dosePopulation: 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.
Outcome measures
| Measure |
Pilot Study 1: TAK-438ASA
n=12 Participants
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=12 Participants
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|
|
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
|
0.7818 l/h
Standard Deviation 0.29682
|
—
|
—
|
|
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
|
0.1022 l/h
Standard Deviation 0.055826
|
—
|
—
|
Adverse Events
Pilot Study 1: TAK-438ASA
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Pilot Study 1: TAK-438 and Aspirin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Pivotal Study 1: TAK-438ASA
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Pivotal Study 1: TAK-438 and Aspirin
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Study 2: TAK-438ASA Fasted
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Study 2: TAK-438ASA Fed
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Pilot Study 1: TAK-438ASA
n=24 participants at risk
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pilot Study 1: TAK-438 and Aspirin
n=23 participants at risk
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438ASA
n=237 participants at risk
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Pivotal Study 1: TAK-438 and Aspirin
n=239 participants at risk
TAK-438 10 mg, tablet and aspirin 100 mg, tablet (free combination), orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Study 2: TAK-438ASA Fasted
n=12 participants at risk
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fasted condition, once on Day 1 of either Period 1 or 2.
|
Study 2: TAK-438ASA Fed
n=12 participants at risk
TAK-438 10 mg and aspirin 100 mg FDC (TAK-438ASA), tablet, orally, under fed condition, once on Day 1 of either Period 1 or 2.
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
4.2%
1/24 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/237 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/239 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
8.3%
1/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
2.5%
6/237 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.84%
2/239 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.84%
2/237 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/239 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
|
Investigations
Liver function test abnormal
|
0.00%
0/24 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/23 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/237 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.42%
1/239 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
0.00%
0/12 • Treatment-emergent adverse events are adverse events (AE) that started after the first dose of study drug and no more than 2 days after the last dose of study drug in Period 2 (Day 18)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Two participants discontinued the study due to an AE in Period 2 pre-dose and did not receive the study drug for Period 2.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
- Publication restrictions are in place
Restriction type: OTHER