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A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01825876
First received: April 3, 2013
Last updated: June 27, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Healthy Volunteers
Drug: Evacetrapib
Drug: Warfarin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Evacetrapib on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of S-Warfarin [ Time Frame: Baseline to 144 hours following warfarin dose on study days 1 and 17 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of S-Warfarin [ Time Frame: Baseline to 144 hours following warfarin dose on study days 1 and 17 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of R-Warfarin [ Time Frame: Baseline to 144 hours following warfarin dose on study days 1 and 17 ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of R-Warfarin [ Time Frame: Baseline to 144 hours following warfarin dose on study days 1 and 17 ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD): Area Under the International Normalized Ratio Curve (AUCINR) of Warfarin [ Time Frame: Baseline to 144 hours following warfarin dose on study days 1 and 17 ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD): Maximum Observed INR Response (INRmax) of Warfarin [ Time Frame: Baseline to 144 hours following warfarin dose on study days 1 and 17 ] [ Designated as safety issue: No ]

Estimated Enrollment: 17
Study Start Date: April 2013
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Warfarin
15 milligram (mg) warfarin administered as a single oral dose
Drug: Warfarin
Oral administration
Experimental: Evacetrapib + Warfarin
130 milligram (mg) evacetrapib administered once daily (QD), orally, for 16 days with 15 milligram (mg) warfarin co-administered once orally on Day 10
Drug: Evacetrapib
Oral administration
Other Name: LY2484595
Drug: Warfarin
Oral administration

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01825876

Locations
United States, Wisconsin
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01825876     History of Changes
Other Study ID Numbers: 14616, I1V-MC-EIAO
Study First Received: April 3, 2013
Last Updated: June 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Evacetrapib
Warfarin
Anticholesteremic Agents
Anticoagulants
Antimetabolites
Hematologic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014