A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants
Study Details
Study Description
Brief Summary
All study participants will receive both warfarin and a study drug called evacetrapib. The main purpose of this study is to look at how much warfarin gets into the blood stream and how long it takes the body to get rid of warfarin when given both with and without evacetrapib. Another purpose is to evaluate the effectiveness of warfarin therapy to prevent blood clots when given with evacetrapib by measuring the time it takes for blood to clot and comparing it to an average of the international normalized ratio (INR). INR measures the time it takes for blood to clot and compares it to an average.
The study will last approximately 5 weeks, not including screening.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Warfarin 15 milligrams (mg) warfarin administered as a single oral dose |
Drug: Warfarin
Oral administration
|
Experimental: Evacetrapib + Warfarin 130 mg evacetrapib administered once daily (QD), orally, for 16 days with 15 mg warfarin co-administered once orally on Day 10 |
Drug: Evacetrapib
Oral administration
Other Names:
Drug: Warfarin
Oral administration
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of S-Warfarin [Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose]
- PK: Maximum Observed Concentration (Cmax) of S-Warfarin [Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose]
Secondary Outcome Measures
- PK: AUC0-∞ of R-Warfarin [Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose]
- PK: Cmax of R-Warfarin [Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose]
- Pharmacodynamics (PD): Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin [Days 1 and 17: 0, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose]
The INR is a standardized ratio of the prothrombin time (PT), time it takes for blood to clot. AUCINR is the time curve used to measure change in INR over time.
- PD: Maximum Observed INR Response (INRmax) of Warfarin [0, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose on Days 1 and 17]
The INR is a standardized ratio of the PT, time it takes for blood to clot.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
-
A medical history and physical examination consistent with a being a healthy individual
-
Male participants will use a reliable method of birth control (as deemed by the investigator) and not donate sperm during the study and for 3 months following the last dose of the investigational product
-
Female participants are not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical hysterectomy, bilateral oophorectomy, or tubal ligation) confirmed by medical history, or post-menopausal
-
Have a body mass index (BMI) of 18 to 32 kilograms per square meter (kg/m^2)
-
Participants are predicted to be cytochrome P450 2C9 (CYP2C9) extensive metabolizers as determined by genotyping assessment
Exclusion Criteria:
-
Have an abnormality in the 12-lead electrocardiogram (ECG) that increases the risks associated with participating in the study
-
Have an abnormal supine blood pressure
-
Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
-
Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
-
Show evidence of hepatitis C and/or positive hepatitis C antibody or evidence of hepatitis B and/or positive hepatitis B surface antigen
-
Women who are pregnant or are lactating
-
Have used or intend to use over-the-counter or prescription medications (including vitamins/mineral supplements, herbal medicine) 14 days prior to enrollment and during the study
-
Have consumed grapefruit, cranberries, or grapefruit- or cranberry-containing products within 7 days prior to the first dose of warfarin
-
Have a history or presence of significant bleeding disorders that is, hematemesis, melanena, severe or recurrent epistaxis, hemoptysis, clinically overt hematuria or intracranial hemorrhage, gastrointestinal ulcers with hemorrhage
-
Have a personal or family history of coagulation or bleeding disorders or reasonable suspicion of vascular malformations, for example, cerebral hemorrhage, aneurysm or premature stroke (cerebrovascular accident at <65 years of age)
-
Have a history of major head trauma (with loss of consciousness) within the past year or minor head trauma (without loss of consciousness) within the last 3 months prior to screening or history of major surgery within 3 months of screening
-
Have planned surgery within 14 days after the last day of dosing
-
Have an international normalized ratio/prothrombin time (INR/PT), or activated partial thromboplastin time (aPTT) above the normal reference range or abnormal Protein S antigen and/or Protein C activity at screening
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Madison | Wisconsin | United States | 53704 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 14616
- I1V-MC-EIAO
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
---|---|---|
Arm/Group Description | 15 milligram (mg) warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered once daily (QD), orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Period Title: Period 1 | ||
STARTED | 17 | 0 |
Received 1 Dose of Study Drug | 17 | 0 |
COMPLETED | 17 | 0 |
NOT COMPLETED | 0 | 0 |
Period Title: Period 1 | ||
STARTED | 0 | 17 |
Received 1 Dose of Study Drug | 0 | 17 |
COMPLETED | 0 | 16 |
NOT COMPLETED | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Overall Study |
---|---|
Arm/Group Description | Participants were administered 15 mg warfarin as a single oral dose on Days 1 and 17; 130 mg evacetrapib was administered QD, orally, on Days 7 to 22. |
Overall Participants | 17 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
38.2
(9.4)
|
Sex: Female, Male (Count of Participants) | |
Female |
1
5.9%
|
Male |
16
94.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
4
23.5%
|
Not Hispanic or Latino |
13
76.5%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
4
23.5%
|
White |
13
76.5%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
17
100%
|
Outcome Measures
Title | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of S-Warfarin |
---|---|
Description | |
Time Frame | Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received a dose of study drug and had evaluable data for AUC(0-∞). |
Arm/Group Title | Warfarin | Evacetrapib + Warfarin |
---|---|---|
Arm/Group Description | 15 mg warfarin administered as a single oral dose | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Measure Participants | 17 | 16 |
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*h/mL)] |
132
(35)
|
126
(39)
|
Title | PK: Maximum Observed Concentration (Cmax) of S-Warfarin |
---|---|
Description | |
Time Frame | Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received a dose of study drug and had evaluable data for Cmax. |
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
---|---|---|
Arm/Group Description | 15 mg warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Measure Participants | 17 | 16 |
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)] |
4.69
(20)
|
4.72
(15)
|
Title | PK: AUC0-∞ of R-Warfarin |
---|---|
Description | |
Time Frame | Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received a dose of study drug and had evaluable data for AUC(0-∞). |
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
---|---|---|
Arm/Group Description | 15 mg warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Measure Participants | 17 | 16 |
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
321
(25)
|
314
(25)
|
Title | PK: Cmax of R-Warfarin |
---|---|
Description | |
Time Frame | Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received a dose of study drug and had evaluable data for Cmax. |
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
---|---|---|
Arm/Group Description | 15 mg warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Measure Participants | 17 | 16 |
Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
6.02
(19)
|
6.22
(15)
|
Title | Pharmacodynamics (PD): Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin |
---|---|
Description | The INR is a standardized ratio of the prothrombin time (PT), time it takes for blood to clot. AUCINR is the time curve used to measure change in INR over time. |
Time Frame | Days 1 and 17: 0, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received a dose of study drug and had evaluable data for AUCINR. |
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
---|---|---|
Arm/Group Description | 15 mg warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Measure Participants | 16 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [ratio*h] |
167
(7.9)
|
162
(5.2)
|
Title | PD: Maximum Observed INR Response (INRmax) of Warfarin |
---|---|
Description | The INR is a standardized ratio of the PT, time it takes for blood to clot. |
Time Frame | 0, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose on Days 1 and 17 |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received a dose of study drug and had evaluable data for INRmax. |
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib + 15 mg Warfarin |
---|---|---|
Arm/Group Description | 15 mg warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 |
Measure Participants | 17 | 16 |
Geometric Mean (Geometric Coefficient of Variation) [ratio] |
1.36
(17.4)
|
1.25
(12.9)
|
Adverse Events
Time Frame | ||||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | 15 mg Warfarin | 130 mg Evacetrapib | 130 mg Evacetrapib + 15 mg Warfarin | |||
Arm/Group Description | 15 mg warfarin administered as a single oral dose on Day 1 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 | 130 mg evacetrapib alone administered QD, orally, on Days 7 to 22 and with 15 mg warfarin co-administered once orally on Day 17 | |||
All Cause Mortality |
||||||
15 mg Warfarin | 130 mg Evacetrapib | 130 mg Evacetrapib + 15 mg Warfarin | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
15 mg Warfarin | 130 mg Evacetrapib | 130 mg Evacetrapib + 15 mg Warfarin | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
15 mg Warfarin | 130 mg Evacetrapib | 130 mg Evacetrapib + 15 mg Warfarin | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/17 (29.4%) | 2/17 (11.8%) | 4/16 (25%) | |||
Blood and lymphatic system disorders | ||||||
Lymphadenopathy | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/16 (6.3%) | 1 |
Gastrointestinal disorders | ||||||
Constipation | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/16 (0%) | 0 |
General disorders | ||||||
Vessel puncture site haemorrhage | 2/17 (11.8%) | 3 | 0/17 (0%) | 0 | 2/16 (12.5%) | 2 |
Infections and infestations | ||||||
Tooth abscess | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/16 (6.3%) | 1 |
Injury, poisoning and procedural complications | ||||||
Contusion | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/16 (0%) | 0 |
Nail injury | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/16 (0%) | 0 |
Nervous system disorders | ||||||
Headache | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 1/16 (6.3%) | 2 |
Skin and subcutaneous tissue disorders | ||||||
Acne | 0/17 (0%) | 0 | 1/17 (5.9%) | 1 | 0/16 (0%) | 0 |
Ecchymosis | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/16 (0%) | 0 |
Erythema | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/16 (0%) | 0 |
Papule | 1/17 (5.9%) | 1 | 0/17 (0%) | 0 | 0/16 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Chief Medical Officer |
---|---|
Organization | Eli Lilly and Company |
Phone | 800-545-5979 |
- 14616
- I1V-MC-EIAO