Skip to main content
OpenTrials
Completed

NCT Number: NCT01111331

Drug Drug Interaction of Empagliflozin (BI 10773) and Warfarin in Healthy Volunteers

The objective of the current study is to investigate the bioavailability of BI 10773 and of warfarin after concomitant multiple oral administration of BI 10773 and a single oral dose of warfarin in comparison to BI 10773 and warfarin given alone, and to investigate the pharmacodynamics of a single oral dose of warfarin with and without concomitant multiple oral administration of BI 10773.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy

Age range

18 year–55 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

1245.18.1 Boehringer Ingelheim Investigational Site

Biberach, Germany

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Healthy male subjects

Treatment and study plan

BI 10773 25 mg

Drug

25 mg BI 10773 qd for 5 days

Warfarin 25 mg

Drug

25 mg Warfarin single dose

Warfarin

Drug

25 mg warfarin single dose with and without 50 mg BI 10773

Primary outcomes

  1. Empagliflozin: Area Under the Curve for the Dosing Interval at Steady State (AUCτ,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin.

    Area under the plasma concentration-time curve for the dosing interval τ at steady state

    In addition to the specified time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  2. Empagliflozin: Maximum Measured Concentration at Steady State(Cmax,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin.

    Maximum measured plasma concentration of empagliflozin (empa) for the dosing interval τ at steady state.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  3. Warfarin R-enantiomers: Area Under the Curve 0 to Infinity (AUC0-∞)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the plasma concentration-time curve from time of dosing extrapolated to infinity.

  4. Warfarin R-enantiomers: Maximum Measured Concentration (Cmax)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Maximum measured concentration of the analyte in plasma.

  5. Warfarin S-enantiomers: Area Under the Curve 0 to Infinity (AUC0-∞)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the plasma concentration-time curve from time of dosing extrapolated to infinity.

  6. Warfarin S-enantiomers: Maximum Measured Concentration (Cmax)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Maximum measured concentration of the analyte in plasma

Secondary outcomes

  1. Empagliflozin: Plasma Concentration 24 Hours After Administration of Dose (C24,N)

    Time frame: 24 hours after dose 4 or 6 respectively (day 5 and day 7)

    Plasma concentration of empagliflozin (empa) measured 24 hours after administration of the fourth dose (Cpre,5) and after the sixth dose (Cpre,7).

  2. Empagliflozin: Terminal Rate Constant at Steady State (λz,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin.

    Terminal rate constant of empagliflozin (empa) in plasma at steady state.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  3. Empagliflozin: Terminal Half-life at Steady State (t1/2,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin.

    Terminal half-life of empagliflozin (empa) in plasma at steady state.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  4. Empagliflozin: Time to Maximum Plasma Concentration at Steady State (Tmax,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin

    Time from last dosing to maximum plasma concentration at steady state over a uniform dosing interval τ.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  5. Empagliflozin: Mean Residence Time at Steady State After Oral Administration (MRTpo,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin.

    Mean residence time of empagliflozin (empa) in the body at steady state after oral administration.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  6. Empagliflozin: Apparent Clearance at Steady State (CL/F,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin.

    Apparent clearance in plasma after extravascular administration at steady state.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  7. Empagliflozin: Apparent Volume of Distribution Following Extravascular Administration (Vz/F,ss)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h post-dose on Day 5 for for empa; 0h, 20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h for empa plus warfarin

    Apparent volume of distribution during the terminal phase at steady state following extravascular administration.

    In addition to the below time frame, pre-dose samples were collected on Days 1, 3, and 4 for empa and a post-dose sample on day 1 for empa plus warfarin.

  8. Warfarin R-enantiomers: Area Under the Curve 0 to Last Measurable Data Point (AUC0-tz)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the plasma concentration-time curve from time of dosing to time of last measurable data point.

  9. Warfarin R-enantiomers: Time to Maximum Plasma Concentration (Tmax)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Time from dosing until maximum plasma concentration is reached

  10. Warfarin R-enantiomers: Terminal Rate Constant (λz)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Terminal rate constant in plasma

  11. Warfarin R-enantiomers: Terminal Half-life (t1/2)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Terminal half-life of the analyte in plasma

  12. Warfarin R-enantiomers: Mean Residence Time After Oral Administration (MRTpo)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Mean residence time of the analyte in the body after oral administration

  13. Warfarin R-enantiomers: Apparent Clearance After Extravascular Administration (CL/F)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Apparent clearance in plasma after extravascular administration

  14. Warfarin R-enantiomers: Apparent Volume of Distribution Following Extravascular Administration (Vz/F)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Apparent volume of distribution during the terminal phase λz following extravascular administration

  15. Warfarin S-enantiomers: Area Under the Curve 0 to Last Measurable Data Point (AUC0-tz)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the plasma concentration-time curve from time of dosing to time of last measurable data point.

  16. Warfarin S-enantiomers: Time to Maximum Plasma Concentration (Tmax)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Time from dosing until maximum plasma concentration is reached

  17. Warfarin S-enantiomers: Terminal Rate Constant (λz)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Terminal rate constant in plasma

  18. Warfarin S-enantiomers: Terminal Half-life (t1/2)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Terminal half-life of the analyte in plasma

  19. Warfarin S-enantiomers: Mean Residence Time After Oral Administration (MRTpo)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Mean residence time of the analyte in the body after oral administration

  20. Warfarin S-enantiomers: Apparent Clearance After Extravascular Administration (CL/F)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Apparent clearance in plasma after extravascular administration

  21. Warfarin S-enantiomers: Apparent Volume of Distribution Following Extravascular Administration (Vz/F)

    Time frame: 0 hours (h), 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Apparent volume of distribution during the terminal phase λz following extravascular administration

  22. Warfarin: Peak International Normalised Ratio (INRmax)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Peak international normalised ratio for warfarin, measured as the maximum INR over time.

  23. Warfarin: Area Under the INR-time Curve From 0 to Last Measurable Data Point (INR AUEC0-tz)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the concentration time curve of the INR measurements over the time interval from 0 to the time of the last quantifiable data point.

  24. Warfarin: Peak International Normalised Ratio Adjusted to Baseline (INRmax,Base)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Peak international normalised ratio for warfarin adjusted for baseline value (before any trial drug administration) of peak international normalised ratio

  25. Warfarin: Peak Prothrombin Time (PTmax)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Peak prothrombin time

  26. Warfarin: Area Under the INR-time Curve From 0 to Last Measurable Data Point Adjusted to Baseline (INR AUEC0-tz,Base)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the INR-time curve from time of dosing to time of last measurable data point adjusted for baseline value (before any trial drug administration) of area under the INR-time curve

  27. Warfarin: Area Under the PT-time Curve From 0 to Last Measurable Data Point (PT AUEC0-tz)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the PT-time curve from time of dosing to time of last measurable data point

  28. Warfarin: Peak Prothrombin Time Adjusted to Baseline (PTmax,Base)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Peak prothrombin time adjusted for baseline value (before any trial drug administration) of peak prothrombin

  29. Warfarin: Area Under the PT-time Curve From 0 to Last Measurable Data Point Adjusted to Baseline (PT AUEC0-tz,Base)

    Time frame: 0 hours (h), 1h, 2h, 4h, 8h, 12h, 24h, 36h, 48h, 72h, 96h, 120h, 144h, 168h after administration of warfarin for both warfarin alone and warfarin plus empagliflozin

    Area under the PT-time curve from time of dosing to time of last measurable data point adjusted for baseline value (before any trial drug administration) of area under the PT-time curve

  30. Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by Investigator

    Time frame: Drug administration until beginning of next sequence/end of trial, 35 days

    Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry and assessment of tolerability by investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

Relative Bioavailability of Both BI 10773 and Warfarin and Pharmacodynamics of Warfarin After Co-administration Compared to Multiple Oral Doses of BI 10773 (25 mg Once Daily) and a Single Oral Dose of Warfarin (25 mg) Alone in Healthy Male Volunteers (an Open-label, Crossover, Clinical Phase I Study)

Important dates

Study start
2010
Primary completion
2010
First posted
Apr 27, 2010
Registry last updated
Jul 23, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.