Trial Outcomes & Findings for Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants (NCT NCT02161731)
NCT ID: NCT02161731
Last Updated: 2018-10-03
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose
Results posted on
2018-10-03
Participant Flow
Participant milestones
| Measure |
Warfarin
15 milligram (mg) warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
Evacetrapib administered once daily (QD), orally, for 16 days on Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
Period 1 (Day -1 to Day 7 Predose)
STARTED
|
24
|
0
|
|
Period 1 (Day -1 to Day 7 Predose)
Received 1 Dose of Study Drug
|
24
|
0
|
|
Period 1 (Day -1 to Day 7 Predose)
COMPLETED
|
24
|
0
|
|
Period 1 (Day -1 to Day 7 Predose)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (Day 7 Dosing to Day 23)
STARTED
|
0
|
24
|
|
Period 2 (Day 7 Dosing to Day 23)
Received 1 Dose of Study Drug
|
0
|
24
|
|
Period 2 (Day 7 Dosing to Day 23)
COMPLETED
|
0
|
22
|
|
Period 2 (Day 7 Dosing to Day 23)
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Warfarin
15 milligram (mg) warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
Evacetrapib administered once daily (QD), orally, for 16 days on Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
Period 2 (Day 7 Dosing to Day 23)
Withdrawal by Subject
|
0
|
1
|
|
Period 2 (Day 7 Dosing to Day 23)
Adverse Event
|
0
|
1
|
Baseline Characteristics
Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants
Baseline characteristics by cohort
| Measure |
Warfarin Then Evacetrapib + Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1. Evacetrapib administered QD, orally, for 16 days, Days 7- 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|
|
Age, Continuous
|
36.0 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 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
|
3 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
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dosePopulation: All participants who received a dose of study drug and had evaluable data for AUC \[0-∞\].
Outcome measures
| Measure |
Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
n=23 Participants
Evacetrapib administered QD, orally, for 16 days, Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of S-Warfarin
|
128 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 23
|
114 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 19
|
PRIMARY outcome
Timeframe: Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dosePopulation: All participants who received a dose of study drug and had evaluable data for Cmax.
Outcome measures
| Measure |
Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
n=23 Participants
Evacetrapib administered QD, orally, for 16 days, Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
PK: Maximum Observed Concentration (Cmax) of S-warfarin
|
4.20 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 21
|
4.34 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 29
|
SECONDARY outcome
Timeframe: Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dosePopulation: All participants who received a dose of study drug and had evaluable data for AUC\[0-∞\].
Outcome measures
| Measure |
Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
n=23 Participants
Evacetrapib administered QD, orally, for 16 days, Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
PK: AUC[0-∞] of R-warfarin
|
287 ng*h/mL
Geometric Coefficient of Variation 16
|
271 ng*h/mL
Geometric Coefficient of Variation 17
|
SECONDARY outcome
Timeframe: Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dosePopulation: All participants who received a dose of study drug and had evaluable data for Cmax of R- enantiomers of Warfarin.
Outcome measures
| Measure |
Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
n=23 Participants
Evacetrapib administered QD, orally, for 16 days, Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
PK: Cmax of R-warfarin
|
5.03 ng/mL
Geometric Coefficient of Variation 21
|
5.27 ng/mL
Geometric Coefficient of Variation 27
|
SECONDARY outcome
Timeframe: Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dosePopulation: All participants who received a dose of study drug and had evaluable data for AUC\[INR\].
The INR is a standardized ratio of the prothrombin time (PT), time it takes for blood to clot. AUC\[INR\] is the time curve used to measure change in INR over time.
Outcome measures
| Measure |
Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
n=23 Participants
Evacetrapib administered QD, orally, for 16 days, Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
Pharmacodynamics (PD): Area Under the International Normalized Ratio Curve (AUC[INR]) of Warfarin
|
174 ratio times hour (ratio*h)
Geometric Coefficient of Variation 7.0
|
165 ratio times hour (ratio*h)
Geometric Coefficient of Variation 5.0
|
SECONDARY outcome
Timeframe: Days 1 and 17: 0, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dosePopulation: All participants who received a dose of study drug and had evaluable date for INRmax.
Outcome measures
| Measure |
Warfarin
n=24 Participants
15 mg warfarin administered as a single oral dose on Day 1.
|
Evacetrapib + Warfarin
n=23 Participants
Evacetrapib administered QD, orally, for 16 days, Days 7 - 22 with 15 mg warfarin co-administered once orally on Day 17.
|
|---|---|---|
|
PD: Maximum Observed International Normalized Ratio Response (INRmax) of Warfarin
|
1.47 ratio
Geometric Coefficient of Variation 18
|
1.34 ratio
Geometric Coefficient of Variation 11
|
Adverse Events
15 mg Warfarin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
130 mg Evacetrapib
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
15 mg Warfarin + 130 mg Evacetrapib
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
15 mg Warfarin
n=24 participants at risk
15 milligram (mg) warfarin administered as a single oral dose on Day 1.
|
130 mg Evacetrapib
n=24 participants at risk
130 mg Evacetrapib administered once daily (QD), orally, for 16 days, Days 7 - 22.
|
15 mg Warfarin + 130 mg Evacetrapib
n=23 participants at risk
Evacetrapib administered once daily (QD), orally, for 16 days, Days 7 - 22 with 15 milligram (mg) warfarin co-administered once orally on Day 17.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/24
|
8.3%
2/24 • Number of events 3
|
0.00%
0/23
|
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