Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to examine the effect of gemfibrozil, ketoconazole, and clarithromycin on how much LY2409021 is found in the bloodstream and how long the body takes to get rid of it. The study is split into two parts, Part A and Part B. Participants in Part A are divided into two cohorts (groups). Each cohort will participate in two study periods. Period 1 involves a single dose of LY2409021. Period 2 involves either gemfibrozil or ketoconazole given daily for 21 days with LY2409021 given once on Day 4. Part A will last for 51 days and will also involve screening within 27 days of the start of the study. Part B is only open to participants who successfully completed Part A of the study. Participants in Part B will receive clarithromycin given daily for 21 days with LY2409021 given once on Day 4. Part B will last for 29 days and will also involve screening within 27 days of the start of the study.
Detailed description
Part B was added to the trial in August 2013, per protocol amendment.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants are overtly healthy males or females, as determined by medical history and physical examination * Participants have a body mass index (BMI) of 18.0 to 32.0 kilograms per meter squared (kg/m\^2), inclusive, at screening * Participants have a fasting blood glucose of 54 to 110 milligrams per deciliter (mg/dL) (3.0 to 6.1 micromoles per liter \[mmol/L\])
Exclusion criteria
* Participants that have a contraindication to use of clarithromycin * Participants that have a personal or family history of long QT syndrome * Participants with a family history of sudden unexplained death or cardiac death in an immediate family member under 60 years of age * Participants with a personal history of unexplained syncope within the last year * Participants who have taken drugs or substances known to be an inducer or inhibitor of cytochrome P450 (CYP)3A4 or CYP2C8 or CYP2J2 (for example, St. John's wort, rifampin, ketoconazole, trimethoprim) within 30 days prior to the first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only) |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only) |
Countries
United States
Participant flow
Pre-assignment details
This study was conducted in 2 parts at a single center as an inpatient and outpatient study. Part A was an open-label, fixed sequence, 2-period, 2-cohort study. Part B was an open-label, 1-period study. Participants who completed Part A were eligible to participate in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: LY2409021+Gemfibrozil (Cohort 1) Part A, Period 1. Participants received a single 20-milligram (mg) oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a morning (AM) and evening (PM) oral dose of 600 mg gemfibrozil on Days 1-20 and an AM oral dose only of 600 mg gemfibrozil on Day 21. Participants also received a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28. | 15 |
| Part A: LY2409021+Ketoconazole (Cohort 2) Part A, Period 1. Participants received a single 20-mg oral dose of LY2409021 on Day 1.
Part A, Period 2. Participants received a once-daily 400-mg oral dose of ketoconazole on Days 1-21 and a single 20-mg oral dose of LY2409021 on Day 4. There was a washout period from Day 22 through Day 28. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A, Period 2 | Protocol Violation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: LY2409021+Ketoconazole (Cohort 2) | Part A: LY2409021+Gemfibrozil (Cohort 1) |
|---|---|---|---|
| Age, Continuous | 39.1 years STANDARD_DEVIATION 11 | 39.5 years STANDARD_DEVIATION 11.6 | 38.7 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 15 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 9 Participants | 8 Participants |
| Region of Enrollment United States | 30 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 30 Participants | 15 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 15 | 1 / 15 | 5 / 15 | 5 / 15 | 2 / 15 | 9 / 15 | 1 / 12 | 8 / 12 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021
Time frame: Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
Population: All participants who received at least 1 dose of study drug and had evaluable AUC(0-∞) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Only (Part A, Cohort 1) | Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | 34700 nanogram*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 31 |
| LY2409021+Gemfibrozil (Part A, Cohort 1) | Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | 35300 nanogram*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 35 |
| LY2409021 Only (Part A, Cohort 2) | Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | 38000 nanogram*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 21 |
| LY2409021+Ketoconazole (Part A, Cohort 2) | Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | 145000 nanogram*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 23 |
| LY2409021 Only (Part B Participants, Data From Part A) | Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | 37400 nanogram*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| LY2409021+Clarithromycin (Part B) | Pharmacokinetics: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of LY2409021 | 43900 nanogram*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 28 |
Primary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
Time frame: Predose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 144, 216, and 336 hours postdose (and 408, 504, and 576 hours postdose in Part A, Period 2 and Part B only)
Population: All participants who received at least 1 dose of study drug and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Only (Part A, Cohort 1) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 431 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| LY2409021+Gemfibrozil (Part A, Cohort 1) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 410 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| LY2409021 Only (Part A, Cohort 2) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 445 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| LY2409021+Ketoconazole (Part A, Cohort 2) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 471 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| LY2409021 Only (Part B Participants, Data From Part A) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 419 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| LY2409021+Clarithromycin (Part B) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 467 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |