Clinical trial NCT02780622: A Pharmacokinetics, Pharmacodynamics and Safety Study of Warfarin in Combination With Tamiflu (Oseltamivir)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Drug Therapy, Combination
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-05-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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 their warfarin followed oseltamivir and warfarin, or by oseltamivir and warfarin followed by warfarin. The treatment periods will be separated by a washout period of at least 4 days. Participants will continue receiving warfarin once daily at a prescribed usual dose throughout the study.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for International Normalized Ratio (INR)
timeFrame: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
measure: Change From Baseline in Maximum Observed Effect (Emax) of International Normalized Ratio (INR)
timeFrame: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
measure: Time to Reach Maximum Change From Baseline in International Normalized Ratio (INR) (Tmax)
timeFrame: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
measure: Area Under the Plasma Effect-time Curve Over 96 Hours (AUEC[0-96 h]) for Factor VII Activity
timeFrame: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
measure: Change From Baseline in Maximum Observed Effect (Emax) in Factor VII Activity
timeFrame: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
measure: Time to Reach Maximum Change From Baseline in Factor VII Activity (Tmax)
timeFrame: Pre-dose on Day 1, 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 96 hours (Day 5)
measure: Change From Baseline in Plasma Concentration of Vitamin K1
timeFrame: Pre-dose on Day 1 and 24 hours post-dose on Day 5
Secondary outcomes:
measure: Time to Maximum Plasma Concentration (Tmax) for Oseltamivir and Oseltamivir Carboxylate
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 5
measure: Time to Maximum Plasma Concentration (Tmax) for R- and S- Warfarin
timeFrame: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5
measure: Terminal Half-life (t½) for Oseltamivir and Oseltamivir Carboxylate
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 5
measure: Terminal Half-life (t½) for R- and S- Warfarin
timeFrame: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5
measure: Oral Plasma Clearance (CL/F) for Oseltamivir
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 5
measure: Oral Plasma Clearance (CL/F) for R- and S- Warfarin
timeFrame: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5
measure: Maximum Plasma Concentration (Cmax) for Oseltamivir and Oseltamivir Carboxylate
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 5
measure: Maximum Plasma Concentration (Cmax) for R- and S- Warfarin
timeFrame: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5
measure: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for Oseltamivir and Oseltamivir Carboxylate
timeFrame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18 and 24 hours post-dose on Day 5
measure: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) for R- and S- Warfarin
timeFrame: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5
measure: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for Oseltamivir and Oseltamivir Carboxylate
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 5
measure: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 12 Hours (AUC0-12h) for R- and S- Warfarin
timeFrame: Pre-dose; 1, 2, 4, 8, 12, 24 hours post-dose on Day 5
measure: Percentage of Participants With Adverse Events
timeFrame: Up to Day 26
Other outcomes:
Locations:
city: Surrey
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: