Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of R-warfarin and S-warfarin
| Group | Value (nanograms times hours per milliliter) | Spread |
|---|---|---|
| Warfarin Alone | 19200 | 24 |
| Dulaglutide + Warfarin | 18900 | 22 |
Trial · Interventional
CompletedPhase 1Results postedRegistry dataUnited States
1 trial · 1 completed · 1 with posted results
A Study of the Effect of Dulaglutide on the Action of Warfarin in Healthy Participants
NCT01432938Sept 2011 to Dec 2011
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
Warfarin is a commonly used drug to prevent the blood from clotting. The purpose of this study is to determine if dulaglutide (LY2189265) affects how warfarin works. The study involves two different treatments (Treatment 1: warfarin; Treatment 2: dulaglutide + warfarin) separated by a minimum washout period of 24 days. In Treatment 1, the participant will receive 10 milligrams (mg) of warfarin on Day 1. In Treatment 2, the participant will receive a 1.5-mg dose of dulaglutide (LY2189265) as an injection on Day 1 and then a 10 mg dose of warfarin on Day 3. Participants will be randomly assigned into different treatment sequences. Participants in Treatment Sequence A will receive Treatment 1 then Treatment 2. Participants in Treatment Sequence B will receive Treatment 2 then Treatment 1.
Experimental
Warfarin first, then Dulaglutide + Warfarin
A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 (Treatment 1). There was a washout period of at least 24 days between treatment periods. Then a single, 1.5-mg dose of dulaglutide administered subcutaneously on Day 1, followed by a single, 10-mg dose of warfarin administered orally on Day 3 (Treatment 2).
Experimental
Dulaglutide + Warfarin first, then Warfarin
A single, 1.5-mg subcutaneous dose of dulaglutide on Day 1, followed by a single, 10-mg oral dose of warfarin on Day 3 (Treatment 2). There was a washout period of at least 24 days between treatment periods. Then a single, 10-mg oral dose of warfarin on Day 1 (Treatment 1).
Outcomes the sponsor listed as primary.
Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of R-warfarin and S-warfarin
Time frame · Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)
Area under the concentration versus time curve (AUC) from zero to infinity was determined from plasma concentrations of the S- and R- enantiomers of warfarin.
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of R-warfarin and S-warfarin
Time frame · Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)
Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-warfarin and S-warfarin
Time frame · Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)
Pharmacodynamics: Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin
Time frame · Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)
AUCINR was assessed from venous blood samples collected to determine the response variable INR at predose and at pre-determined intervals after the administration of warfarin.
Pharmacodynamics: Maximum Observed International Normalized Ratio (INRmax) of Warfarin
Time frame · Predose (warfarin) and up to 144 hours postdose on Day 1 for Treatment 1 (warfarin alone) and on Day 3 for Treatment 2 (warfarin in combination with dulaglutide)
Observed INRmax was assessed from venous blood samples collected to determine the response variable INR at predose and at pre-determined intervals after the administration of warfarin.
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value (nanograms times hours per milliliter) | Spread |
|---|---|---|
| Warfarin Alone | 19200 | 24 |
| Dulaglutide + Warfarin | 18900 | 22 |
| Group | Value (nanograms per milliliter (ng/mL)) | Spread |
|---|---|---|
| Warfarin Alone | 530 | 19 |
| Dulaglutide + Warfarin | 414 | 23 |
| Group | Value (hours) |
|---|---|
| Warfarin Alone | 2.00 |
| Dulaglutide + Warfarin | 4.00 |
| Group | Value (ratio) | Spread |
|---|---|---|
| Warfarin Alone | 157 | 5 |
| Dulaglutide + Warfarin | 161 | 5 |
| Group | Value (ratio) | Spread |
|---|---|---|
| Warfarin Alone | 1.24 | 13 |
| Dulaglutide + Warfarin | 1.27 | 15 |
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Warfarin AloneA single, 10-milligram (mg) dose administered orally on Day 1 of Treatment 1. Timeframe: Treatment 1 | – | 0 / 28 | 3 / 28 |
| Dulaglutide AloneA single, 1.5-mg dose administered subcutaneously on Day 1 of Treatment 2. Timeframe: Day 1 to Day 3 before dosing of warfarin in Treatment 2 | – | 0 / 26 | 5 / 26 |
| Dulaglutide + WarfarinA single, 1.5-mg dose of dulaglutide administered subcutaneously on Day 1 of Treatment 2, followed by a single, 10-mg dose of warfarin administered orally on Day 3 of Treatment 2 Timeframe: After dosing of warfarin on Day 3 of Treatment 2 | – | 0 / 25 | 4 / 25 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies that cite this trial.
1 study on this page
Indexing hint: Randomized controlled trial · 2017
de la Peña et al. 2017Clinical pharmacokineticscited by 22
PMID 28357715DOI 10.1007/s40262-017-0531-7PUB-28357715
Who could join, as posted.
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