A Study of LY2484595 in Healthy Subjects

Single Dose LY2484595 Tablet Formulations to Determine the Impact of Dose Level, Food, and Ethnicity on the Pharmacokinetics in Healthy Subjects

The purpose of this study will be to evaluate the safety of a single dose of LY2484595 and to compare the amount of LY2484595 in the blood of healthy non-Asian subjects, Chinese subjects, and first-generation Japanese subjects after receiving a single oral dose of LY2484595 in a fasted state, after eating a low-fat meal, and after eating a high-fat meal.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG); Drug: LY2484595 Reference Formulation (RF)

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • 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 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are overtly healthy males or females, as determined by medical history and physical examination. For Cohort B, a first-generation Japanese subject is defined as one who is Japanese and was born in Japan and whose parents and all grandparents are Japanese and were born in Japan. A first-generation Chinese subject is defined as one who is Chinese and was born in China (mainland or Taiwan) and whose parents and all grandparents are Chinese and were born in China
• Female subjects are not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they are at least age 45, have had cessation of menses for at least 1 year, and have not taken hormones or oral contraceptives (including estrogen or hormone replacement therapy) during the past 12 months
• Have a body mass index (BMI) of 18.5 to 29.0 kilograms per meter squared (kg/m^2), inclusive
• Have clinical laboratory test results within normal reference range for the population or investigator site or results with acceptable deviations that are judged to be not clinically significant by the investigator
• Have an acceptable blood pressure (BP) and heart rate at both supine and standing positions as determined by the investigator (systolic BP less than or equal to 140 millimeters of mercury [mmHg], and diastolic BP less than or equal to 90 mmHg). A single, repeat BP measurement may be done at the discretion of the investigator
• Have venous access sufficient to allow blood sampling
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
• Have given written informed consent approved by Eli Lilly and Company (hereafter, Lilly) and the ethical review board (ERB) governing the site

Exclusion Criteria:

• Are currently enrolled in or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have known allergies to LY2484595 or related compounds
• Are persons who have previously completed or withdrawn from this study
• Have an abnormality in the 12-lead electrocardiogram (ECG) (including but not limited to a Bazett's corrected QT [QTcB] interval >450 milliseconds (msec) for men and >470 msec for women) that, in the opinion of the investigator, increases the risks associated with participating in the study
• Have a history within the last 2 years or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic 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 significant active neuropsychiatric disease
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening
• Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies
• Show evidence of hepatitis C and/or positive hepatitis C antibody
• Show evidence of hepatitis B and/or positive hepatitis B surface antigen
• Are women with a positive pregnancy test or women who are lactating
• Intend to use and actually use over-the-counter or prescription medication or dietary supplements within 14 days prior to dosing (acetaminophen is permissible on an as-needed basis at less than 3 grams per day for less than 7 days)
• Have donated blood of more than 500 milliliters (mL) within the last month
• Have an average alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption for 48 hours prior and during the inpatient confinement at the Clinical Research Unit (CRU) (1 unit = 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
• Use herbal supplements, grapefruit juice, grapefruits, Seville orange juice, Seville oranges, or starfruit within 7 days prior to study dosing
• Smoke more than 10 cigarettes per day currently and are unwilling to abide by the CRU guidelines
• Are unwilling to refrain from daily consumption of real licorice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort A: Fixed Sequence of Meal Conditions; LY2484595 (evacetrapib): 200 milligrams (mg) of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with no food. There was a washout of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with low-fat breakfast. There was another washout period of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with high-fat breakfast.	Drug: LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG); Administered orally; Other Names: Evacetrapib
EXPERIMENTAL: Cohort B: Comparison of Randomized Treatments; LY2484595 (evacetrapib): 100 mg of LY2484595 administered orally as an RF tablet given with a low-fat breakfast. There was a washout period of at least 14 days before crossing over and receiving 100 mg of LY2484595 administered orally as a SDSD-PG tablet given with a low-fat breakfast. There was another washout of at least 14 days before crossing over and receiving 300 mg of LY2484595 as a SDSD-PG tablet given with a low-fat breakfast.	Drug: LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG); Administered orally; Other Names: Evacetrapib; Drug: LY2484595 Reference Formulation (RF); Administered orally; Other Names: Evacetrapib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595	Area under the concentration-time curve from time zero to infinity is presented.	Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose
Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595		Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs	Data presented are the number of participants who experienced one or more drug-related AEs or any serious AEs. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	Baseline through completion of study (approximately 2 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: October 7, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (ESTIMATE): October 12, 2011

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: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Antioxidants; Evacetrapib; Propyl Gallate
• Other Study ID Numbers: 13697; I1V-MC-EIAJ (OTHER: Eli Lilly and Company)