Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants

Effect of Evacetrapib on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Warfarin; Drug: Evacetrapib

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 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, melena, 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 less than 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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Warfarin; 15 milligram (mg) warfarin administered as a single oral dose on Day 1	Drug: Warfarin; Oral administration
Experimental: Evacetrapib + Warfarin; Evacetrapib administered once daily (QD), orally, for 16 days with 15 mg warfarin co-administered once orally on Day 17	Drug: Warfarin; Oral administration; Drug: Evacetrapib; Oral administration; Other Names: LY2484595

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) 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

Outcome Measure	Measure Description	Time Frame
PK: AUC[0-∞] 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 (AUC[INR]) of Warfarin	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.	Days 1 and 17: 0, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose
PD: Maximum Observed International Normalized Ratio Response (INRmax) of Warfarin		Days 1 and 17: 0, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours following warfarin dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 10, 2014
• First Posted (Estimate): June 12, 2014

Study Record Updates

• Last Update Posted (Actual): October 3, 2018
• Last Update Submitted That Met QC Criteria: February 18, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Anticoagulants; Warfarin; Evacetrapib
• Other Study ID Numbers: 15366; I1V-MC-EIBN (Other Identifier: Eli Lilly and Company)