Healthy Volunteers
Conditions
Brief summary
The purpose of this study will be to evaluate the safety of a single dose of LY2484595 and to compare the amount of LY2484595 in the blood of healthy non-Asian subjects, Chinese subjects, and first-generation Japanese subjects after receiving a single oral dose of LY2484595 in a fasted state, after eating a low-fat meal, and after eating a high-fat meal.
Interventions
DRUGLY2484595 Reference Formulation (RF)
Administered orally
DRUGLY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG)
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
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females, as determined by medical history and physical examination. For Cohort B, a first-generation Japanese subject is defined as one who is Japanese and was born in Japan and whose parents and all grandparents are Japanese and were born in Japan. A first-generation Chinese subject is defined as one who is Chinese and was born in China (mainland or Taiwan) and whose parents and all grandparents are Chinese and were born in China * Female subjects are not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they are at least age 45, have had cessation of menses for at least 1 year, and have not taken hormones or oral contraceptives (including estrogen or hormone replacement therapy) during the past 12 months * Have a body mass index (BMI) of 18.5 to 29.0 kilograms per meter squared (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 an acceptable blood pressure (BP) and heart rate at both supine and standing positions as determined by the investigator (systolic BP less than or equal to 140 millimeters of mercury \[mmHg\], and diastolic BP less than or equal to 90 mmHg). A single, repeat BP measurement may be done at the discretion of the investigator * Have venous access sufficient to allow 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 Eli Lilly and Company (hereafter, Lilly) and the ethical review board (ERB) governing the site
Exclusion criteria
* Are currently enrolled in or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug or device 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 * Are persons who have previously completed or withdrawn from this study * Have an abnormality in the 12-lead electrocardiogram (ECG) (including but not limited to a Bazett's corrected QT \[QTcB\] interval \>450 milliseconds (msec) for men and \>470 msec for women) that, in the opinion of the investigator, increases the risks associated with participating in the study * Have a history within the last 2 years or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic 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 * Show evidence of significant active neuropsychiatric disease * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Show evidence of human immunodeficiency virus (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 * Intend to use and actually use over-the-counter or prescription medication or dietary supplements within 14 days prior to dosing (acetaminophen is permissible on an as-needed basis at less than 3 grams per day for less than 7 days) * Have donated blood of more than 500 milliliters (mL) within the last month * Have an average alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption for 48 hours prior and during the inpatient confinement at the Clinical Research Unit (CRU) (1 unit = 12 ounces \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits) * Use herbal supplements, grapefruit juice, grapefruits, Seville orange juice, Seville oranges, or starfruit within 7 days prior to study dosing * Smoke more than 10 cigarettes per day currently and are unwilling to abide by the CRU guidelines * Are unwilling to refrain from daily consumption of real licorice
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595 | Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose | Area under the concentration-time curve from time zero to infinity is presented. |
| Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595 | Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs | Baseline through completion of study (approximately 2 months) | Data presented are the number of participants who experienced one or more drug-related AEs or any serious AEs. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Fixed Sequence of Meal Conditions LY2484595: 200 milligrams (mg) of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with no food. There was a washout of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with low-fat breakfast. There was another washout period of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with high-fat breakfast. | 8 |
| Cohort B: Comparison of Randomized Treatments LY2484595: 100 mg of LY2484595 administered orally as an RF tablet given with a low-fat breakfast. There was a washout period of at least 14 days before crossing over and receiving 100 mg of LY2484595 administered orally as an SDSD-PG tablet given with a low-fat breakfast. There was another washout of at least 14 days before crossing over and receiving 300 mg of LY2484595 as a SDSD-PG tablet given with a low-fat breakfast. | 31 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 3 | Protocol Violation | 0 | 1 |
| Period 3 | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Cohort B: Comparison of Randomized Treatments | Total | Cohort A: Fixed Sequence of Meal Conditions |
|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 11.4 | 36.2 years STANDARD_DEVIATION 10.73 | 32.0 years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 36 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian (Chinese) | 10 Participants | 10 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian (Japanese) | 11 Participants | 11 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 12 Participants | 6 Participants |
| Region of Enrollment United States | 31 Participants | 39 Participants | 8 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 0 Participants |
| Sex: Female, Male Male | 25 Participants | 33 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 | 3 / 8 | 4 / 31 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 8 | 0 / 31 |
Outcome results
Primary
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595
Area under the concentration-time curve from time zero to infinity is presented.
Time frame: Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose
Population: All participants in Cohort A who received at least 1 dose of study drug with evaluable LY2484595 plasma concentration data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2484595 200 mg SDSD-PG Fasted | Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595 | 12200 hours times nanograms per milliliter | Geometric Coefficient of Variation 29 |
| LY2484595 200 mg SDSD-PG Low Fat | Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595 | 17800 hours times nanograms per milliliter | Geometric Coefficient of Variation 31 |
| LY2484595 200 mg SDSD-PG High Fat | Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595 | 17800 hours times nanograms per milliliter | Geometric Coefficient of Variation 29 |
Primary
Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595
Time frame: Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose
Population: All participants in Cohort A who received at least 1 dose of study drug with evaluable LY2484595 maximum observed plasma concentration data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2484595 200 mg SDSD-PG Fasted | Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595 | 828 nanograms per milliliter | Geometric Coefficient of Variation 51 |
| LY2484595 200 mg SDSD-PG Low Fat | Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595 | 1510 nanograms per milliliter | Geometric Coefficient of Variation 30 |
| LY2484595 200 mg SDSD-PG High Fat | Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595 | 1280 nanograms per milliliter | Geometric Coefficient of Variation 28 |
Secondary
Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs
Data presented are the number of participants who experienced one or more drug-related AEs or any serious AEs. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through completion of study (approximately 2 months)
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2484595 200 mg SDSD-PG Fasted | Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs | 0 participants |
| LY2484595 200 mg SDSD-PG Low Fat | Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs | 0 participants |
| LY2484595 200 mg SDSD-PG High Fat | Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs | 2 participants |
| LY2484595 300 mg SDSD-PG | Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs | 1 participants |