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

NCT01825876 | Completed Phase 1 Results

• 2 other identifiers: 14616I1V-MC-EIAO
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

• 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

Study Arms (2)

Warfarin

ACTIVE COMPARATOR

15 milligrams (mg) warfarin administered as a single oral dose

Drug: Warfarin

Evacetrapib + Warfarin

EXPERIMENTAL

130 mg evacetrapib administered once daily (QD), orally, for 16 days with 15 mg warfarin co-administered once orally on Day 10

Drug: Evacetrapib; Drug: Warfarin

Interventions

Evacetrapib DRUG

Oral administration

Also known as: LY2484595

Evacetrapib + Warfarin

Warfarin DRUG

Oral administration

Evacetrapib + Warfarin; Warfarin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (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, 53704, United States

Location

MeSH Terms

Interventions

evacetrapib; Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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 DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: April 8, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: October 9, 2018
• Results First Posted: October 9, 2018

Record last verified: 2018-02

Locations

US (1)