A Study of LY2484595 on Pharmacokinetics in Healthy Participants

NCT ID: NCT01448824

Last Updated: 2019-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2012-02-29

Brief 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.

Detailed Description

This study is a 2-part, multiple ascending dose (MAD) and drug drug interaction (DDI) study to evaluate the safety and tolerability and the effect of cytochrome P450 (CYP) 3A inhibition by ketoconazole on the pharmacokinetics of LY2484595 in healthy participants.

In the MAD portion (Part 1) of this study, participants in 4 cohorts (Cohorts A through D) will be randomized to receive either LY2484595 (5 ascending dose levels [100 to 1800 mg]) or placebo. Cohorts will have staggered starts ≥7 days from the previous cohort to allow for review of safety and tolerability. The total duration of Part 1 is approximately 13 weeks including screening.

Participants in Cohort A will participate in 2 periods separated by a washout period lasting ≥14 days. During Period 1, participants will receive the starting dose of LY2484595 (100 mg) or placebo once daily (QD) for 14 consecutive days. During Period 2, participants will receive the highest dose of LY2484595 (1800 mg) or placebo QD for 14 consecutive days. Participants will complete a follow-up visit ≥14 days after the last dose of study drug.

Participants in Cohorts B, C, and D will receive LY2484595 (300, 600, and 1200 mg LY2484595, respectively) or placebo QD for 14 consecutive days followed by a follow-up visit ≥14 days after last dose of study drug.

The DDI portion of this study (Part 2) will be open label and consist of 2 periods. The total duration of Part 2 is approximately 10 weeks. LY2484595 (100 mg) will be administered on Day 1 of Period 1 and on Day 5 of Period 2. In Period 2, ketoconazole (400 mg) will be administered QD for 14 consecutive days (13 days alone [Days 1 through 4 and 6 through 14] + 1 day with LY2484595 [Day 5]). There will be a ≥14-day washout period between dosing during Period 1 and Period 2. Participants will return for a follow-up visit ≥14 days after last dose of study drug.

Conditions

Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Part 1 (Cohort A): 100 mg, 1800 mg LY2484595, Placebo

Period 1: Participants will receive either 100 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14 of Period 1.

Washout period lasting ≥14 days.

Period 2: Participants will receive either 1800 mg LY2484595 tablets or placebo tablets QD by mouth on Days 1 through 14 of Period 2.

Group Type: EXPERIMENTAL

LY2484595

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Part 1 (Cohort B): 300 mg LY2484595, Placebo

Participants will receive either 300 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14.

Group Type: EXPERIMENTAL

LY2484595

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Part 1 (Cohort C): 600 mg LY2484595, Placebo

Participants will receive either 600 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14.

Group Type: EXPERIMENTAL

LY2484595

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Part 1 (Cohort D): 1200 mg LY2484595, Placebo

Participants will receive either 1200 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14.

Group Type: EXPERIMENTAL

LY2484595

Intervention Type: DRUG

Administered orally

Placebo

Intervention Type: DRUG

Administered orally

Part 2 (Cohort E): 100 mg LY2484595 ± 400 mg Ketoconazole

Period 1: Participants will receive 100 milligrams (mg) LY2484595 tablet by mouth on Day 1 of Period 1.

Washout period lasting ≥14 days.

Period 2: Participants will receive 400 mg ketoconazole tablets once daily (QD) by mouth on Days 1 through 14 of Period 2. Participants will receive 100 mg LY2484595 tablet by mouth on Day 5 of Period 2.

Group Type: EXPERIMENTAL

LY2484595

Intervention Type: DRUG

Administered orally

Ketoconazole

Intervention Type: DRUG

Administered orally

Interventions

LY2484595

Administered orally

Intervention Type: DRUG

Placebo

Administered orally

Intervention Type: DRUG

Ketoconazole

Administered orally

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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.

Daytona Beach, Florida, United States

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.

Dallas, Texas, United States

Countries

United States

Other Identifiers

I1V-MC-EIAL

Identifier Type: OTHER

Identifier Source: secondary_id

14460

Identifier Type: -

Identifier Source: org_study_id