Trial Outcomes & Findings for A Study of the Effect of Dulaglutide on the Action of Warfarin in Healthy Participants (NCT NCT01432938)
NCT ID: NCT01432938
Last Updated: 2014-10-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
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)
Results posted on
2014-10-07
Participant Flow
Participant milestones
| Measure |
Warfarin First, Then Dulaglutide + Warfarin
First Intervention: 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.
Second Intervention: A single, 1.5-mg subcutaneous dose of dulaglutide on Day 1, followed by a single, 10-mg dose of warfarin administered orally on Day 3 (Treatment 2).
|
Dulaglutide + Warfarin First, Then Warfarin
First Intervention: A single, 1.5-mg subcutaneous dose of dulaglutide on Day 1, followed by a single, 10-mg dose of warfarin administered orally on Day 3 (Treatment 2).
There was a washout period of at least 24 days between intervention periods.
Second Intervention: A single, 10-mg dose of warfarin administered orally on Day 1 (Treatment 1).
|
|---|---|---|
|
First Intervention
STARTED
|
14
|
14
|
|
First Intervention
Received at Least 1 Dose of Study Drug
|
14
|
14
|
|
First Intervention
COMPLETED
|
12
|
14
|
|
First Intervention
NOT COMPLETED
|
2
|
0
|
|
Washout Period of at Least 24 Days
STARTED
|
12
|
14
|
|
Washout Period of at Least 24 Days
COMPLETED
|
12
|
14
|
|
Washout Period of at Least 24 Days
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
12
|
14
|
|
Second Intervention
COMPLETED
|
11
|
14
|
|
Second Intervention
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Warfarin First, Then Dulaglutide + Warfarin
First Intervention: 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.
Second Intervention: A single, 1.5-mg subcutaneous dose of dulaglutide on Day 1, followed by a single, 10-mg dose of warfarin administered orally on Day 3 (Treatment 2).
|
Dulaglutide + Warfarin First, Then Warfarin
First Intervention: A single, 1.5-mg subcutaneous dose of dulaglutide on Day 1, followed by a single, 10-mg dose of warfarin administered orally on Day 3 (Treatment 2).
There was a washout period of at least 24 days between intervention periods.
Second Intervention: A single, 10-mg dose of warfarin administered orally on Day 1 (Treatment 1).
|
|---|---|---|
|
First Intervention
Protocol Violation
|
1
|
0
|
|
First Intervention
Physician Decision
|
1
|
0
|
|
Second Intervention
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Study of the Effect of Dulaglutide on the Action of Warfarin in Healthy Participants
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=28 Participants
Participants who received at least one dose of study drug (dulaglutide or warfarin).
|
|---|---|
|
Age, Continuous
|
44.2 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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)Population: Participants who received at least one dose of warfarin with evaluable warfarin concentration data.
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.
Outcome measures
| Measure |
Warfarin Alone
n=28 Participants
A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 of Treatment 1.
|
Dulaglutide + Warfarin
n=25 Participants
A 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.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of R-warfarin and S-warfarin
S-warfarin
|
19200 nanograms times hours per milliliter
Geometric Coefficient of Variation 24
|
18900 nanograms times hours per milliliter
Geometric Coefficient of Variation 22
|
|
Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of R-warfarin and S-warfarin
R-warfarin
|
33000 nanograms times hours per milliliter
Geometric Coefficient of Variation 25
|
32900 nanograms times hours per milliliter
Geometric Coefficient of Variation 24
|
PRIMARY outcome
Timeframe: 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)Population: Participants who received at least one dose of warfarin with evaluable warfarin concentration data.
Outcome measures
| Measure |
Warfarin Alone
n=28 Participants
A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 of Treatment 1.
|
Dulaglutide + Warfarin
n=25 Participants
A 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.
|
|---|---|---|
|
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of R-warfarin and S-warfarin
S-warfarin
|
530 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 19
|
414 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
|
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of R-warfarin and S-warfarin
R-warfarin
|
530 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 18
|
451 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 19
|
PRIMARY outcome
Timeframe: 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)Population: Participants who received at least one dose of warfarin with evaluable warfarin concentration data.
Outcome measures
| Measure |
Warfarin Alone
n=28 Participants
A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 of Treatment 1.
|
Dulaglutide + Warfarin
n=25 Participants
A 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.
|
|---|---|---|
|
Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-warfarin and S-warfarin
S-warfarin
|
2.00 hours
Interval 1.0 to 4.0
|
4.00 hours
Interval 1.0 to 24.02
|
|
Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-warfarin and S-warfarin
R-warfarin
|
2.00 hours
Interval 1.0 to 4.0
|
8.00 hours
Interval 2.0 to 24.02
|
SECONDARY outcome
Timeframe: 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)Population: Participants who received at least one dose of warfarin with evaluable warfarin INR data.
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.
Outcome measures
| Measure |
Warfarin Alone
n=28 Participants
A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 of Treatment 1.
|
Dulaglutide + Warfarin
n=25 Participants
A 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.
|
|---|---|---|
|
Pharmacodynamics: Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin
|
157 ratio
Geometric Coefficient of Variation 5
|
161 ratio
Geometric Coefficient of Variation 5
|
SECONDARY outcome
Timeframe: 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)Population: Participants who received at least 1 dose of warfarin with evaluable warfarin INR data.
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.
Outcome measures
| Measure |
Warfarin Alone
n=28 Participants
A single, 10-milligram (mg) dose of warfarin administered orally on Day 1 of Treatment 1.
|
Dulaglutide + Warfarin
n=25 Participants
A 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.
|
|---|---|---|
|
Pharmacodynamics: Maximum Observed International Normalized Ratio (INRmax) of Warfarin
|
1.24 ratio
Geometric Coefficient of Variation 13
|
1.27 ratio
Geometric Coefficient of Variation 15
|
Adverse Events
Warfarin Alone
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Dulaglutide Alone
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Dulaglutide + Warfarin
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Warfarin Alone
n=28 participants at risk
A single, 10-milligram (mg) dose administered orally on Day 1 of Treatment 1.
Timeframe: Treatment 1
|
Dulaglutide Alone
n=26 participants at risk
A 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
|
Dulaglutide + Warfarin
n=25 participants at risk
A 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
|
|---|---|---|---|
|
Eye disorders
Vision blurred
|
0.00%
0/28
|
3.8%
1/26 • Number of events 1
|
0.00%
0/25
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/28
|
3.8%
1/26 • Number of events 1
|
0.00%
0/25
|
|
Gastrointestinal disorders
Diarrhoea
|
3.6%
1/28 • Number of events 1
|
0.00%
0/26
|
8.0%
2/25 • Number of events 2
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/28
|
3.8%
1/26 • Number of events 1
|
0.00%
0/25
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/28
|
0.00%
0/26
|
4.0%
1/25 • Number of events 1
|
|
Gastrointestinal disorders
Lip dry
|
3.6%
1/28 • Number of events 1
|
0.00%
0/26
|
0.00%
0/25
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/28
|
7.7%
2/26 • Number of events 2
|
4.0%
1/25 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/28
|
11.5%
3/26 • Number of events 3
|
0.00%
0/25
|
|
General disorders
Fatigue
|
0.00%
0/28
|
3.8%
1/26 • Number of events 1
|
0.00%
0/25
|
|
General disorders
Injection site pain
|
0.00%
0/28
|
0.00%
0/26
|
4.0%
1/25 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
3.6%
1/28 • Number of events 1
|
0.00%
0/26
|
0.00%
0/25
|
|
Injury, poisoning and procedural complications
Procedural dizziness
|
3.6%
1/28 • Number of events 2
|
0.00%
0/26
|
0.00%
0/25
|
|
Investigations
Lipase increased
|
0.00%
0/28
|
3.8%
1/26 • Number of events 1
|
0.00%
0/25
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/28
|
7.7%
2/26 • Number of events 2
|
0.00%
0/25
|
|
Nervous system disorders
Headache
|
0.00%
0/28
|
7.7%
2/26 • Number of events 2
|
0.00%
0/25
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/28
|
3.8%
1/26 • Number of events 3
|
0.00%
0/25
|
|
Nervous system disorders
Somnolence
|
3.6%
1/28 • Number of events 1
|
3.8%
1/26 • Number of events 1
|
0.00%
0/25
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60