Trial Outcomes & Findings for A Pharmacokinetics, Pharmacodynamics and Safety Study of Warfarin in Combination With Tamiflu (Oseltamivir) (NCT NCT02780622)
NCT ID: NCT02780622
Last Updated: 2016-10-26
Results Overview
INR is calculated based on results of a prothrombin time (PT) test (which measures how long it takes blood to clot) and is used to monitor individuals who are being treated with the blood-thinning medication (anticoagulant) warfarin. The net AUEC(0-96 h) was calculated using the linear trapezoidal rule; this was the area under the effect-time curve and above the baseline minus the area above the curve and below the baseline during the 5-day period. An increase in INR signifies enhancement of warfarin's anticoagulant effect.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
20 participants
Primary outcome timeframe
Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
Results posted on
2016-10-26
Participant Flow
Participant milestones
| Measure |
First Warfarin Then Warfarin and Oseltamivir
Participants received warfarin (on Days 1-5) in Treatment Period 1, followed by a washout period of at least 4 days (maximum 8 days). Participants then received oseltamivir 75 milligram (mg) (orally twice daily on Days 1-4 and once on Day 5) and warfarin in Treatment Period 2, and attended a follow-up visit 4-12 days after the last dose in Treatment Period 2. Participants continued to receive warfarin once daily at a prescribed usual dose throughout the study.
|
First Warfarin and Oseltamivir Then Warfarin
Participants received oseltamivir 75 mg (orally twice daily on Days 1-4 and once on Day 5) and warfarin in Treatment Period 1, followed by a washout period of at least 4 days (maximum 8 days). Participants then received warfarin (on Days 1-5) in Treatment Period 2, and attended a follow-up visit 4-12 days after the last dose in Treatment Period 2. Participants continued to receive warfarin once daily at a prescribed usual dose throughout the study.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
10
|
10
|
|
Treatment Period 1
COMPLETED
|
10
|
10
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
10
|
10
|
|
Treatment Period 2
COMPLETED
|
10
|
10
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pharmacokinetics, Pharmacodynamics and Safety Study of Warfarin in Combination With Tamiflu (Oseltamivir)
Baseline characteristics by cohort
| Measure |
All Participants
n=20 Participants
Participants were randomized to 1 of 2 treatment sequences: warfarin then oseltamivir 75 mg and warfarin; or oseltamivir 75 mg and warfarin then warfarin.
|
|---|---|
|
Age, Continuous
|
62.4 years
STANDARD_DEVIATION 8.82 • n=99 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)Population: All enrolled participants.
INR is calculated based on results of a prothrombin time (PT) test (which measures how long it takes blood to clot) and is used to monitor individuals who are being treated with the blood-thinning medication (anticoagulant) warfarin. The net AUEC(0-96 h) was calculated using the linear trapezoidal rule; this was the area under the effect-time curve and above the baseline minus the area above the curve and below the baseline during the 5-day period. An increase in INR signifies enhancement of warfarin's anticoagulant effect.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for International Normalized Ratio (INR)
|
-2.16 hours*ratio
Interval -27.6 to 78.0
|
-9.06 hours*ratio
Interval -93.6 to 18.0
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)Population: All enrolled participants.
INR is calculated based on results of a prothrombin time (PT) test (which measures how long it takes blood to clot) and is used to monitor individuals who are being treated with the blood-thinning medication (anticoagulant) warfarin. An increase in INR signifies enhancement of warfarin's anticoagulant effect.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Maximum Observed Effect (Emax) of International Normalized Ratio (INR)
|
0.3 ratio
Interval 0.0 to 2.1
|
0.1 ratio
Interval 0.0 to 0.5
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)Population: All enrolled participants.
INR is calculated based on results of a prothrombin time (PT) test (which measures how long it takes blood to clot) and is used to monitor individuals who are being treated with the blood-thinning medication (anticoagulant) warfarin. An increase in INR signifies enhancement of warfarin's anticoagulant effect.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Time to Reach Maximum Change From Baseline in International Normalized Ratio (INR) (Tmax)
|
24.00 hours
Interval 0.0 to 96.0
|
0.00 hours
Interval 0.0 to 96.0
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)Population: All enrolled participants with available data.
Factor VIIa is a protein that causes blood to clot, and low levels in the blood can cause excessive or prolonged bleeding after an injury or surgery. The net AUEC(0-96 h) was calculated using the linear trapezoidal rule; this was the area under the effect-time curve and above the baseline minus the area above the curve and below the baseline during the 5-day period. A decrease in factor VIIa activity signifies enhancement of warfarin's anticoagulant effect. kIU/L = 1000 \* international units per liter.
Outcome measures
| Measure |
Warfarin
n=19 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=19 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for Factor VII Activity
|
0.568 hours*kIU/L
Interval -9.48 to 7.56
|
1.45 hours*kIU/L
Interval -5.16 to 12.5
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)Population: All enrolled participants with available data.
Factor VIIa is a protein that causes blood to clot. A decrease in factor VIIa activity signifies enhancement of warfarin's anticoagulant effect. kIU/L = 1000 \* international units per liter.
Outcome measures
| Measure |
Warfarin
n=19 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=19 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Maximum Observed Effect (Emax) in Factor VII Activity
|
-0.0505 kIU/L
Interval -0.21 to 0.0
|
-0.0432 kIU/L
Interval -0.15 to 0.0
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)Population: All enrolled participants with available data.
Factor VIIa is a protein that causes blood to clot. A decrease in factor VIIa activity signifies enhancement of warfarin's anticoagulant effect.
Outcome measures
| Measure |
Warfarin
n=19 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=19 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Time to Reach Maximum Change From Baseline in Factor VII Activity (Tmax)
|
96.00 hours
Interval 0.0 to 96.0
|
72.00 hours
Interval 0.0 to 96.0
|
PRIMARY outcome
Timeframe: Pre-dose on Day 1 and 24 hours post-dose on Day 5Population: All enrolled participants.
Vitamin K1 is required by proteins involved in blood clotting. Food interaction with warfarin can lead to decreases in Vitamin K1 in plasma. An increase in vitamin K1 signifies enhancement of warfarin's anticoagulant effect.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Change From Baseline in Plasma Concentration of Vitamin K1
|
305 nanogram per liter (ng/L)
Interval -371.0 to 1060.0
|
271 nanogram per liter (ng/L)
Interval -1100.0 to 1310.0
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1 and 5; 18 and 24 hours post-dose on Day 5Population: All enrolled participants.
Oseltamivir carboxylate is an active metabolite of oseltamivir.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Single Dose: Day 1)
|
0.50 hours
Interval 0.5 to 3.0
|
—
|
|
Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Single Dose: Day 1)
|
4.00 hours
Interval 2.0 to 6.0
|
—
|
|
Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Steady State: Day 5)
|
0.75 hours
Interval 0.5 to 3.0
|
—
|
|
Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Steady State: Day 5)
|
4.00 hours
Interval 3.0 to 6.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin
Total (S)-warfarin
|
2.00 hours
Interval 1.0 to 8.13
|
4.00 hours
Interval 0.0 to 23.92
|
|
Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin
Free (S)-warfarin
|
14.5 hours
Interval 8.74 to 53.8
|
3.01 hours
Interval 1.0 to 8.0
|
|
Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin
Total (R)-warfarin
|
3.00 hours
Interval 1.0 to 11.83
|
4.00 hours
Interval 1.0 to 23.92
|
|
Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin
Free (R)-warfarin
|
4.00 hours
Interval 1.0 to 11.83
|
3.00 hours
Interval 1.0 to 11.83
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1 and 5; 18 and 24 hours post-dose on Day 5Population: All enrolled participants.
Oseltamivir carboxylate is an active metabolite of oseltamivir.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Single Dose: Day 1)
|
1.77 hours
Standard Deviation 0.686
|
—
|
|
Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Single Dose: Day 1)
|
6.17 hours
Standard Deviation 2.07
|
—
|
|
Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Steady State: Day 5)
|
4.00 hours
Standard Deviation 3.08
|
—
|
|
Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Steady State: Day 5)
|
8.19 hours
Standard Deviation 1.90
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Terminal Half-life (t½) for R- and S- Warfarin
Total (S)-warfarin (n = 13, 11)
|
45.4 hours
Standard Deviation 23.0
|
45.6 hours
Standard Deviation 11.7
|
|
Terminal Half-life (t½) for R- and S- Warfarin
Total (R)-warfarin (n = 12, 12)
|
56.1 hours
Standard Deviation 26.1
|
53.6 hours
Standard Deviation 12.2
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1 and 5; 18 and 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Oral Plasma Clearance (CL/F) for Oseltamivir
Oseltamivir (Single Dose: Day 1)
|
558 liters per hour (L/h)
Standard Deviation 134
|
—
|
|
Oral Plasma Clearance (CL/F) for Oseltamivir
Oseltamivir (Steady State: Day 5)
|
463 liters per hour (L/h)
Standard Deviation 104
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Oral Plasma Clearance (CL/F) for R- and S- Warfarin
Total (S)-warfarin
|
0.198 liters per hour (L/h)
Standard Deviation 0.0895
|
0.208 liters per hour (L/h)
Standard Deviation 0.0959
|
|
Oral Plasma Clearance (CL/F) for R- and S- Warfarin
Free (S)-warfarin
|
38.5 liters per hour (L/h)
Standard Deviation 17
|
38.2 liters per hour (L/h)
Standard Deviation 15.1
|
|
Oral Plasma Clearance (CL/F) for R- and S- Warfarin
Total (R)-warfarin
|
0.139 liters per hour (L/h)
Standard Deviation 0.0361
|
0.145 liters per hour (L/h)
Standard Deviation 0.0374
|
|
Oral Plasma Clearance (CL/F) for R- and S- Warfarin
Free (R)-warfarin
|
21.7 liters per hour (L/h)
Standard Deviation 5.74
|
22 liters per hour (L/h)
Standard Deviation 5.54
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1 and 5; 18 and 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Single Dose: Day 1)
|
88.9 nanogram per milliliter (ng/mL)
Standard Deviation 50.0
|
—
|
|
Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Single Dose: Day 1)
|
367 nanogram per milliliter (ng/mL)
Standard Deviation 107
|
—
|
|
Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Steady State: Day 5)
|
91.2 nanogram per milliliter (ng/mL)
Standard Deviation 47.2
|
—
|
|
Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Steady State: Day 5)
|
571 nanogram per milliliter (ng/mL)
Standard Deviation 160
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5Population: All enrolled participants.
R- and S-warfarin are two molecular versions of warfarin with slightly different structures. The reported concentrations were normalized by dividing the Cmax values (nanograms per milliliter) by the individual average dose (milligrams).
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for R- and S- Warfarin
Total (S)-warfarin
|
394 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 259
|
330 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 197
|
|
Maximum Plasma Concentration (Cmax) for R- and S- Warfarin
Free (S)-warfarin
|
1.87 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 1.30
|
1.68 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 1.13
|
|
Maximum Plasma Concentration (Cmax) for R- and S- Warfarin
Total (R)-warfarin
|
436 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 243
|
375 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 96.3
|
|
Maximum Plasma Concentration (Cmax) for R- and S- Warfarin
Free (R)-warfarin
|
2.70 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 1.45
|
2.37 Nanogram/milliliter/milligram (ng/mL/mg)
Standard Deviation 0.604
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Steady state: Day 5)
|
176 h*ng/mL
Standard Deviation 38.5
|
—
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Steady State: Day 5)
|
7180 h*ng/mL
Standard Deviation 2550
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5Population: All enrolled participants.
R- and S-warfarin are two molecular versions of warfarin with slightly different structures. The reported concentrations were normalized by dividing the AUC values (hours multiplied by nanograms, per milliliter) by the individual average dose (milligrams).
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin
Total (S)-warfarin
|
6770 h*ng/mL/mg
Standard Deviation 4500
|
6460 h*ng/mL/mg
Standard Deviation 4310
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin
Free (S)-warfarin
|
35.2 h*ng/mL/mg
Standard Deviation 26.1
|
33.9 h*ng/mL/mg
Standard Deviation 24.1
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin
Total (R)-warfarin
|
7790 h*ng/mL/mg
Standard Deviation 2480
|
7360 h*ng/mL/mg
Standard Deviation 1960
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin
Free (R)-warfarin
|
49.4 h*ng/mL/mg
Standard Deviation 13.4
|
48.3 h*ng/mL/mg
Standard Deviation 11.9
|
SECONDARY outcome
Timeframe: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1 and 5; 18 and 24 hours post-dose on Day 5Population: All enrolled participants.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Single Dose: Day 1)
|
2990 h*ng/mL
Standard Deviation 793
|
—
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Steady State: Day 5)
|
169 h*ng/mL
Standard Deviation 36.3
|
—
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir Carboxylate (Steady State: Day 5)
|
5110 h*ng/mL
Standard Deviation 1630
|
—
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir (Single Dose: Day 1)
|
141 h*ng/mL
Standard Deviation 38.3
|
—
|
SECONDARY outcome
Timeframe: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5Population: All enrolled participants.
R- and S-warfarin are two molecular versions of warfarin with slightly different structures. The reported concentrations were normalized by dividing the AUC values (hours multiplied by nanograms, per milliliter) by the individual average dose (milligrams).
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin
Total (S)-warfarin
|
3610 h*ng/mL/mg
Standard Deviation 2200
|
3380 h*ng/mL/mg
Standard Deviation 2100
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin
Free (S)-warfarin
|
18.6 h*ng/mL/mg
Standard Deviation 13.0
|
17.8 h*ng/mL/mg
Standard Deviation 12.3
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin
Total (R)-warfarin
|
4140 h*ng/mL/mg
Standard Deviation 1320
|
3870 h*ng/mL/mg
Standard Deviation 1020
|
|
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin
Free (R)-warfarin
|
25.9 h*ng/mL/mg
Standard Deviation 7.84
|
24.8 h*ng/mL/mg
Standard Deviation 6.36
|
SECONDARY outcome
Timeframe: Up to Day 26Population: All enrolled participants.
An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Outcome measures
| Measure |
Warfarin
n=20 Participants
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 Participants
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Percentage of Participants With Adverse Events
|
25.0 percentage of participants
|
25.0 percentage of participants
|
Adverse Events
Warfarin
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Warfarin and Oseltamivir
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Warfarin
n=20 participants at risk
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 participants at risk
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
Other adverse events
| Measure |
Warfarin
n=20 participants at risk
Participants who received Warfarin alone at a prescribed usual dose in treatment period 1 or treatment period 2.
|
Warfarin and Oseltamivir
n=20 participants at risk
Participants who received warfarin at a prescribed usual dose along with oseltamivir 75 mg, orally twice daily on Days 1-4 and once on Day 5 in treatment period 1 or treatment period 2.
|
|---|---|---|
|
Infections and infestations
Fungal skin infection
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Infections and infestations
Oral herpes
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Nervous system disorders
Headache
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
10.0%
2/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
General disorders
Venipuncture site swelling
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
5.0%
1/20 • Five days for each treatment period (Up to Day 26)
All enrolled participants.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER