Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of LY2484595 on Pharmacokinetics in Healthy Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01448824
Recruitment Status : Completed
First Posted : October 7, 2011
Results First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE October 6, 2011
First Posted Date  ICMJE October 7, 2011
Results First Submitted Date  ICMJE February 18, 2018
Results First Posted Date  ICMJE April 2, 2019
Last Update Posted Date April 2, 2019
Study Start Date  ICMJE October 2011
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Part 1: Number of Participants With 1 or More Adverse Events (AEs) or Any Serious AEs [ Time Frame: Part 1: Baseline through ≥14 days after last dose of study drug (≥Day 28) ]
    The number of participants with 1 or more AEs is summarized cumulatively. In addition, the number of participants with any serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
  • Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2484595 [ Time Frame: Part 2, Period 1, Day 1 through Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post Dose; Period 2, Day 5 through Day 15: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 Hours Post Dose ]
    The geometric least squares (LS) means for the maximum observed plasma concentration (Cmax) of LY2484595 following administration of LY2484595 alone and with ketoconazole are reported. Least squares means were calculated from an analysis of variance (ANOVA) model with a fixed effect for treatment and a random effect for participant. The LS means for each treatment and the 90% confidence intervals (CI) for the difference in means were back transformed from the log scale to provide estimates of the geometric means and 90% CIs for the ratio of the geometric means (LY2484595 coadministered with ketoconazole and LY2484595 alone).
  • Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) of LY2484595 [ Time Frame: Part 2, Period 1, Day 1 through Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post Dose; Period 2, Day 5 through Day 15: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 Hours Post Dose ]
    The median times to maximum observed plasma concentration (Tmax) of LY2484595 following administration of LY2484595 alone and with ketoconazole are reported.
  • Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2484595 [ Time Frame: Part 2, Period 1, Day 1 through Day 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post Dose; Period 2, Day 5 through Day 15: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 Hours Post Dose ]
    The geometric least squares (LS) means of area under the concentration-time curve (AUC) from time zero extrapolated to infinity (AUC0-∞) of LY2484595 following administration of LY2484595 alone and with ketoconazole are reported. Least squares means were calculated from an analysis of variance (ANOVA) model with a fixed effect for treatment and a random effect for participant. The LS means for each treatment and the 90% confidence intervals (CI) for the difference in means were back transformed from the log scale to provide estimates of the geometric means and 90% CIs for the ratio of the geometric means (LY2484595 coadministered with ketoconazole and LY2484595 alone).
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2011)
  • Part 1: Number of subjects with one or more drug related Adverse Events (AEs) or any Serious AEs [ Time Frame: Part 1: Baseline up to Day 28 ]
  • Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2484595 [ Time Frame: Part 2: Pre-dose up to Day 21 ]
  • Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) of LY2484595 [ Time Frame: Part 2: Pre-dose up to Day 21 ]
  • Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2484595 [ Time Frame: Part 2: Pre-dose up to Day 21 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2019)
  • Pharmacodynamics: Change From Baseline to Day 21 in Cholesteryl Ester Transfer Protein (CETP) Activity [ Time Frame: Day 1 (Baseline) and Day 21 ]
  • Pharmacodynamics: Change From Baseline to Day 21 in High-density Lipoprotein Cholesterol (HDL-C), Low-density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) [ Time Frame: Day 1 (Baseline) and Day 21 ]
  • Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2484595 [ Time Frame: Part 1, Periods 1 and 2, Day 1: Predose, 1, 2, 3, 4, 6, 8, 12, and 24 Hours Postdose; Day 14 through Day 21: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 Hours Post Dose ]
    The maximum observed plasma concentrations (Cmax) of LY2484595 after a single dose and after once daily (QD) dosing for 14 consecutive days are reported.
  • Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) of LY2484595 [ Time Frame: Part 1, Periods 1 and 2, Day 1: Predose, 1, 2, 3, 4, 6, 8, 12, and 24 Hours Postdose; Day 14 through Day 21: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 Hours Post Dose ]
    The times of maximum observed plasma concentrations (tmax) of LY2484595 after a single dose and after once daily (QD) dosing for 14 consecutive days are reported.
  • Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2484595 [ Time Frame: Part 1, Periods 1 and 2, Day 1: Predose, 1, 2, 3, 4, 6, 8, 12, and 24 Hours Postdose; Day 14 through Day 21: Predose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 Hours Post Dose ]
    Exposure to LY2484595 in terms of the area under the concentration-time curves (AUC) after a single dose and after once daily (QD) dosing for 14 consecutive days are reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2011)
  • Pharmacodynamics: Change From Baseline to Day 21 in Cholesteryl Ester Transfer Protein (CETP) Activity [ Time Frame: Part 1: Baseline, up to Day 21 ]
  • Pharmacodynamics: Change From Baseline to Day 21 in High-density Lipoprotein Cholesterol (HDL-C), Low-density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) [ Time Frame: Part 1: Baseline, up to Day 21 ]
  • Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2484595 [ Time Frame: Part 1: Pre-dose up to Day 21 ]
  • Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax) of LY2484595 [ Time Frame: Part 1: Pre-dose up to Day 21 ]
  • Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2484595 [ Time Frame: Part 1: Pre-dose up to Day 21 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of LY2484595 on Pharmacokinetics in Healthy Participants
Official Title  ICMJE A Phase 1 Study to Evaluate the Safety and Tolerability of LY2484595 SDSD-PG Tablets and the Effect of CYP3A Inhibition by Ketoconazole on the Pharmacokinetics of LY2484595 in Healthy Subjects
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Healthy Participants
Intervention  ICMJE
  • Drug: LY2484595
    Administered orally
  • Drug: Placebo
    Administered orally
  • Drug: Ketoconazole
    Administered orally
Study Arms  ICMJE
  • Experimental: 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.

    Interventions:
    • Drug: LY2484595
    • Drug: Placebo
  • Experimental: 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.
    Interventions:
    • Drug: LY2484595
    • Drug: Placebo
  • Experimental: 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.
    Interventions:
    • Drug: LY2484595
    • Drug: Placebo
  • Experimental: 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.
    Interventions:
    • Drug: LY2484595
    • Drug: Placebo
  • Experimental: 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.

    Interventions:
    • Drug: LY2484595
    • Drug: Ketoconazole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 29, 2019)
82
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2011)
60
Actual Study Completion Date  ICMJE February 2012
Actual Primary Completion Date February 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01448824
Other Study ID Numbers  ICMJE 14460
I1V-MC-EIAL ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP