Healthy Volunteers
Conditions
Keywords
Healthy Volunteers, Bioavailability
Brief summary
The purposes of this study are to compare how much of LY2409021 enters the bloodstream and how long the body takes to get rid of the drug when different formulations of LY2409021 are given, and when LY2409021 is taken with or without food. The study will be conducted in 2 cohorts. Each cohort will have 3 study periods consisting of 3 formulations of LY2409021. Participants in each cohort will receive the same all 3 formulations using a randomized sequence crossover design. There is a washout period of at least 14 days between dosing periods. There will be an interim analysis after Cohort 1 completes study Period 2. Cohort 2 will not begin enrolling until this analysis is complete. The need to enroll Cohort 2 will be determined by the outcome of the interim analysis.
Interventions
DRUGLY2409021 Reference Form
Administered orally
DRUGLY2409021 Test-Med Formulation (medium particle size)
Administered orally
DRUGLY2409021 Test-High Formulation (high particle size)
Administered orally
DRUGLY2409021 Test-Low Formulation (low particle size)
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be healthy male or a healthy female who cannot become pregnant * Must have body mass index (BMI) of 18.5 to 32 kilograms per meter squared (kg/m²), inclusive * Blood pressure as well as blood and urine laboratory test results must be acceptable for the study * The veins must be suitable for easy blood collection * Must be willing to be available for the whole study and be willing to follow study procedures
Exclusion criteria
* Were in another new drug or medical research study in the last 30 days * Have previously taken part in this study or any other study with LY2409021 * Have taken LY2409021, or drugs similar to LY2409021 before and was found to be allergic to the drug * Currently have or used to have health problems or laboratory test results that in the opinion of the doctor, could interfere with understanding the results of this study * Electrocardiogram (ECG) readings are not suitable for the study * Are infected with hepatitis B * Are infected with human immunodeficiency disease virus (HIV) * Are using or intend to use over-the-counter medication or prescription medications within 14 days, from the start of the first study dosing until end of study * Have a regular alcohol intake greater than 21 units per week (males) and 14 units per week (females) or are not willing to abstain from alcohol while in the research unit * Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic * Have a history of drug or alcohol abuse * Have donated 450 milliliters (mL) or more of blood in the last 3 months * Are unwilling or unable to comply with dietary requirements/restrictions during the study * The study doctor thinks the participant should not participate for any other reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Medium Test Form to Reference Form | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | AUC from time 0 to infinity (AUC0-∞). |
| Pharmacokinetics, Maximum Concentration (Cmax): Medium Test Form to Reference Form | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics, Time to Maximum Concentration (Tmax) | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | — |
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Standardized High Fat Meal to Fasting | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | AUC from time 0 to infinity (AUC0-∞). |
| Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | — |
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | AUC from time 0 to infinity (AUC0-∞). |
| Pharmacokinetics, Maximum Concentration (Cmax): Standardized High Fat Meal to Fasting | Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose) | — |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2409021 Cohort 1 Participants randomized to 1 of 3 sequences and received a single but different intervention per period: Sequence 1 (reference capsules fasting, then test-medium tablet fasting, then test-medium tablet after high-fat meal), Sequence 2 (test-medium tablet fasting, then test-medium tablet after high-fat meal, then reference capsules fasting), or Sequence 3 (test-medium tablet after high-fat meal, then reference capsules fasting, then test-medium tablet fasting).
There was a washout period of at least 14 days between interventions. Description of interventions: reference capsules fasting \[20-milligram (mg) LY2409021 dose, administered orally, once in fasted state\], test-medium tablet fasting (20-mg LY2409021 tablet, medium particle size, administered orally, once in fasted state), and test-medium tablet after high-fat meal (20-mg LY2409021 tablet, medium particle size, administered orally, once, immediately after standardized high-fat meal). | 18 |
| LY2409021 Cohort 2 Participants randomized to 1 of 3 sequences and received a single but different intervention per period: Sequence 4 (test-medium tablet fasting then, test-high tablet fasting, then test-low tablet fasting), Sequence 5 (test-high tablet fasting then, test-low tablet fasting, then test-medium tablet fasting), or Sequence 6 (test-low tablet fasting, then test-medium tablet fasting, then test-high tablet fasting).
There was a washout period of at least 14 days between interventions. Description of interventions: test-low tablet fasting (single 20-mg LY2409021 tablet of a low particle size, administered orally in a fasted state), test-medium tablet fasting (single 20-mg LY2409021 tablet of a medium particle size, administered orally, once in a fasted state), and test-high tablet fasting (single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state). | 17 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout (at Least 14 Days) | Scheduling Conflict | 0 | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LY2409021 Cohort 2 | Total | LY2409021 Cohort 1 |
|---|---|---|---|
| Age, Continuous | 32.6 years STANDARD_DEVIATION 9.7 | 33.6 years STANDARD_DEVIATION 10.1 | 34.4 years STANDARD_DEVIATION 10.7 |
| Race/Ethnicity, Customized Asian | 17 Participants | 35 Participants | 18 Participants |
| Region of Enrollment Singapore | 17 Participants | 35 Participants | 18 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 33 Participants | 18 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 15 | 17 / 18 | 7 / 15 | 22 / 33 | 9 / 17 |
| serious Total, serious adverse events | 0 / 15 | 0 / 18 | 0 / 15 | 0 / 33 | 0 / 17 |
Outcome results
Primary
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Medium Test Form to Reference Form
AUC from time 0 to infinity (AUC0-∞).
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohort 1 who received the specified study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Medium Test Form to Reference Form | 65300 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Medium Test Form to Reference Form | 62800 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
90% CI: [0.897, 1.18]
Primary
Pharmacokinetics, Maximum Concentration (Cmax): Medium Test Form to Reference Form
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohort 1 who received the specified study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Maximum Concentration (Cmax): Medium Test Form to Reference Form | 779 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Maximum Concentration (Cmax): Medium Test Form to Reference Form | 726 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
90% CI: [0.922, 1.22]
Secondary
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size
AUC from time 0 to infinity (AUC0-∞).
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohort 2 who received the specified study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size | 73700 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 16 |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size | 69400 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 18 |
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size | 73600 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 17 |
90% CI: [0.951, 1.04]
90% CI: [0.905, 0.983]
Secondary
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Standardized High Fat Meal to Fasting
AUC from time 0 to infinity (AUC0-∞).
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohort 1 who received the specified study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Standardized High Fat Meal to Fasting | 67000 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 18 |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Standardized High Fat Meal to Fasting | 65300 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
90% CI: [0.896, 1.16]
Secondary
Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohort 2 who received the specified study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size | 835 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size | 793 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size | 844 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
90% CI: [0.926, 1.04]
90% CI: [0.891, 0.993]
Secondary
Pharmacokinetics, Maximum Concentration (Cmax): Standardized High Fat Meal to Fasting
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohort 1 who received the specified study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Maximum Concentration (Cmax): Standardized High Fat Meal to Fasting | 785 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 14 |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Maximum Concentration (Cmax): Standardized High Fat Meal to Fasting | 779 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
90% CI: [0.882, 1.15]
Secondary
Pharmacokinetics, Time to Maximum Concentration (Tmax)
Time frame: Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)
Population: Randomized participants in Cohorts 1 and 2 who received the specified study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Time to Maximum Concentration (Tmax) | 8.00 hour (hr) |
| LY2409021 Cohort 1 (Reference Capsules Fasted) | Pharmacokinetics, Time to Maximum Concentration (Tmax) | 8.00 hour (hr) |
| LY2409021 Cohort 1 (Test-Medium Tablet Fasted) | Pharmacokinetics, Time to Maximum Concentration (Tmax) | 8.00 hour (hr) |
| LY2409021 Cohort 2 (Test-Low Tablet Fasted) | Pharmacokinetics, Time to Maximum Concentration (Tmax) | 4.00 hour (hr) |
| LY2409021 Cohort 2 (Test-Medium Tablet Fasted) | Pharmacokinetics, Time to Maximum Concentration (Tmax) | 8.00 hour (hr) |
| LY2409021 Cohort 2 (Test-High Tablet Fasted) | Pharmacokinetics, Time to Maximum Concentration (Tmax) | 8.00 hour (hr) |