Participants on Warfarin Therapy Clinical Trial
Official title:
An Open-label, Randomized 2-period Crossover Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Warfarin in Combination With Oseltamivir in Volunteers Stabilized on Warfarin Therapy
| Verified date | June 2016 |
| Source | Hoffmann-La Roche |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
This is an open-label, randomized, 2-period crossover study, to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of warfarin in combination with Tamiflu (oseltamivir) in participants stabilized on warfarin. Participants will be randomized to receive either Treatment A followed by Treatment B (AB) or Treatment B followed by Treatment A (BA) in 2 treatment periods. Treatment A includes participant's usual warfarin therapy, and Treatment B includes warfarin therapy along with repeated doses of oseltamivir twice daily for 4 days, and once on Day 5. The treatment periods will be separated by a washout period of at least 4 days.
| Status | Completed |
| Enrollment | 20 |
| Est. completion date | July 2008 |
| Est. primary completion date | July 2008 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 75 Years |
| Eligibility |
Inclusion Criteria: - Participants must have been receiving warfarin once daily for at least 4 weeks prior to Screening - Participants must have regular International Normalized ratio (INR) monitoring during warfarin therapy prior to study entry, and be willing to be trained in the use of CoaguCheck devices - INR must fall within a target range of 2.0-3.5 - Body mass index (BMI) between 18-32 kg/m^2 inclusive Exclusion Criteria: - An INR value between screening and Day -1 lower than 2.0 or greater than 3.5 - A change in prescribed daily warfarin dose between Screening and Day -1 - History of any coagulopathy - Consumption of health products or supplements containing vitamin K - Pregnant or lactating women - Confirmed positive urine and/or blood test for drugs of abuse at Screening or Day -1 |
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Hoffmann-La Roche |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Maximum International Normalized Ratio (INR) | Days 1 to 5 | No | |
| Primary | Time to Reach Maximum International Normalized Ratio (INR) | Days 1 to 5 | No | |
| Primary | Area Under the Plasma Effect-time Curve (AUEC) for Factor VII Activity | Days 1 to 5 | No | |
| Primary | Area Under the Plasma Effect-time Curve (AUEC) for Minimum Factor VII Activity | Days 1 to 5 | No | |
| Primary | Area Under the Plasma Effect-time Curve (AUEC) for Time to Reach Minimum Factor VII Activity | Days 1 to 5 | No | |
| Primary | Plasma Concentration of Vitamin K1 | Pre-dose on Day 1 and post-dose on Day 6 | No | |
| Primary | Area Under the Plasma Effect-time Curve (AUEC) for International Normalized Ratio (INR) | Days 1 to 5 | No | |
| Secondary | Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate (OC) | 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 5 | No | |
| Secondary | Terminal Half-life (t½) for R- and S- Warfarin | Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5 | No | |
| Secondary | Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate (OC) | 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 5 | No | |
| Secondary | Oral Plasma Clearance (CL/F) for R- and S- Warfarin | Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5 | No | |
| Secondary | Oral Plasma Clearance (CL/F) for Oseltamivir | 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 5 | No | |
| Secondary | Percentage of Participants with Adverse Events | Day 1 up to follow up (Day 22) | No | |
| Secondary | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for Oseltamivir and Oseltamivir Carboxylate (OC) | Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post-dose on Day 5 | No | |
| Secondary | Maximum Plasma Concentration (Cmax) for R- and S- Warfarin | Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5 | No | |
| Secondary | Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate (OC) | 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 5 | No | |
| Secondary | Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin | Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5 | No | |
| Secondary | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin | Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5 | No | |
| Secondary | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate (OC) | 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 5 | No | |
| Secondary | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin | Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5 | No |