A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants
- Registration Number
- NCT01825876
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Evacetrapib + Warfarin Warfarin 130 mg evacetrapib administered once daily (QD), orally, for 16 days with 15 mg warfarin co-administered once orally on Day 10 Warfarin Warfarin 15 milligrams (mg) warfarin administered as a single oral dose Evacetrapib + Warfarin Evacetrapib 130 mg evacetrapib administered once daily (QD), orally, for 16 days with 15 mg warfarin co-administered once orally on Day 10
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
Trial Locations
- Locations (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