A Study of LY2484595 on Pharmacokinetics in Healthy Participants
Condition: Healthy Participants
Intervention: LY2484595; Placebo; Ketoconazole
Intervention description: Administered orally; Administered orally; Administered orally
Intervention MeSH terms: Ketoconazole; Evacetrapib
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 82.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Low High-density Lipoprotein (HDL); Cholesterol (HDL-C)

Summary:

      This is a 2-part study. Part 1 is to determine the safety and tolerability in healthy
      participants of increasing daily doses of LY2484595 for 14 days to achieve a blood level of
      LY2484595 much higher than what is needed for therapy. The amount of study drug that reaches
      the bloodstream and the time it takes for the body to get rid of it will be determined. The
      effect of the study drug on factors in the blood related to cholesterol will be measured.

      Part 2 is to determine how ketoconazole affects how much of the study drug, LY2484595, gets
      into the bloodstream and how long it takes to get rid of it. Information about any side
      effects that may occur will also be collected.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are overtly healthy males or females, as determined by medical history and physical
             examination

          -  Female participants and women not of childbearing potential due to surgical
             sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation) or menopause.
             Postmenopausal is defined as women age >45 with an intact uterus who have not taken
             hormones or oral contraceptives within the last year, and who have had either
             cessation of menses greater than or equal to 1 year or 6 to 12 months of spontaneous
             amenorrhea with follicle-stimulating hormone (FSH) >40 milli-international units per
             milliliter (40 international units per liter [IU/L]).

          -  Have a body mass index (BMI) between 18 to 32 kilograms per square meter (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 venous access sufficient to allow for 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 Lilly and the institutional review
             board (IRB) governing the site

        Exclusion Criteria:

          -  Are currently enrolled in, have completed or discontinued within the last 30 days from
             a clinical trial involving an investigational product, 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, contraindications to
             ketoconazole or related compounds, or allergies to any components of the formulations

          -  Are persons who have previously completed or withdrawn from this study or any other
             study investigating LY2484595 and have previously received the investigational product

          -  Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the
             investigator, increases the risks associated with participating in the study and/or
             poses difficulties in the interpretation of eventual changes occurring during the
             study

          -  Have systolic blood pressure of >140 millimeters of mercury (mmHg) or diastolic blood
             pressure of >90 mmHg

          -  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

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening

          -  Show evidence of human immunodeficiency virus infection (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

          -  Have used or intend to use over-the-counter or prescription medication within 14 days
             prior to dosing unless deemed acceptable by the investigator and sponsor's medical
             monitor

          -  Use of any drugs or substances that are known to be an inducer or inhibitor of
             cytochrome p450 3A4 (CYP3A4) (for example, St. John's wort) within 30 days prior to
             first dose of study drug

          -  Have donated blood of more than 500 milliliters (mL) within 30 days prior to first
             dose of study drug

          -  Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14
             units per week (females) or are unwilling to stop alcohol consumption for the duration
             of the study (1 unit equals 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine;
             1.5 oz or 45 mL of distilled spirits)

          -  Consume 5 or more cups of coffee (or other beverages of comparable caffeine content)
             per day, on a habitual basis, or any subjects unwilling to adhere to study caffeine
             restriction

          -  Have a daily use of greater than or equal to 5 tobacco- or nicotine-containing
             products (including but not limited to cigarettes, pipes, cigars, chewing tobacco,
             nicotine patches, nicotine lozenges, or nicotine gum) and are unwilling to refrain
             from using any tobacco- or nicotine-containing products within 7 days prior to first
             dose through the follow-up visit

          -  Have consumed grapefruit, grapefruit juice, Seville orange, Seville orange juice, or
             starfruit or products that contain these fruits within 7 days prior to first dose and
             during the study

          -  Unwilling to refrain from daily consumption of black licorice containing glycyrrhizic
             acid (that is, real licorice)

          -  In the opinion of the investigator or sponsor, are unsuitable for inclusion in the
             study