Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to determine if two different dosing strategies for evacetrapib will have essentially the same effect on the body. The study will also explore the effect of a low fat meal on how the body absorbs evacetrapib. This study will last at least 15 weeks, not including screening. Screening is required within 28 days prior to the date of first dosing.
Interventions
DRUGEvacetrapib
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
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy Japanese, as determined by medical history and physical examination * Have a body mass index (BMI) of 18.0 to 29.9 kg/m\^2 * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion criteria
* 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 * Have an abnormal supine blood pressure as determined by the investigator * 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 * Are women who are pregnant or lactating * Have used or intend to use over-the-counter, prescription medications, or herbal medicine 14 days prior to enrollment and during the study * Have donated blood of more than 400 mL in the last 12 weeks (males) or in the last 16 weeks (females), or any blood donation (including apheresis) within the last 4 weeks * Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to abide by alcohol restrictions * Are participants who currently smoke more than 10 cigarettes per day or are unwilling to abide by smoking restrictions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Evacetrapib (Fasted) | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 1,2,3, and 4 |
| PK: Maximum Concentration (Cmax) of Evacetrapib (Fasted) | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 1,2,3, and 4 |
Secondary
| Measure | Time frame |
|---|---|
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib (Fasted and Fed) | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 2,4, and 5 |
| PK: AUC(0-∞)of Evacetrapib (Fasted and Fed) | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 2,4, and 5 |
| PK: Cmax of Evacetrapib (Fasted and Fed) | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 2,4, and 5 |
Countries
Japan
Participant flow
Pre-assignment details
Periods 1 to 4 participants are in the fasting state and Period 5 participants were fed a low fat meal. There were two fixed sequences for Test (T) and Reference (R) doses with each participant receiving 5 doses. There was a washout period of at least 21 days between doses.
Participants by arm
| Arm | Count |
|---|---|
| Reference/Test/Reference/Test/Test Reference(R) dose is a single oral dose of Reference 1 one- 130 mg tablet of evacetrapib on Day 1 of Period 1 and Day 1 of Period 3. Then, Test (T) dose is a single oral dose of Test 2 two- 65 mg tablets of evacetrapib on Day 1 of Period 2, Day 1 of Period 4 and Day 1 of Period 5. There was a washout period of at least 21 days between doses. | 24 |
| Test/Reference/Test/Reference/Reference Test (T) dose is a single oral dose of Test 2 two- 65 mg tablets of evacetrapib on Day 1 of Period 1 and Day 1 of Period 3. Then, Reference (R) dose is a single oral dose of Reference 1 one- 130 mg tablet of evacetrapib on Day 1 of Period 2, Day 1 of Period 4 and Day 1 of Period 5. There was a washout period of at least 21 days between doses. | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 2 Fasted State | Lost to Follow-up | 1 | 0 |
| Treatment Period 5 Fed State | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Reference/Test/Reference/Test/Test | Total | Test/Reference/Test/Reference/Reference |
|---|---|---|---|
| Age, Continuous | 33.2 years STANDARD_DEVIATION 9.9 | 33.9 years STANDARD_DEVIATION 10.6 | 34.7 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 48 Participants | 24 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 | 24 Participants | 48 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 24 Participants | 48 Participants | 24 Participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Male | 18 Participants | 36 Participants | 18 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 / 48 | 2 / 48 | 0 / 23 | 2 / 23 |
| serious Total, serious adverse events | 0 / 48 | 0 / 48 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Evacetrapib (Fasted)
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 1,2,3, and 4
Population: All randomized participants who completed and had evaluable AUC(0-∞) bioequivalence fasted state data for Periods 1,2,3 and 4.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference (Fasted) | Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Evacetrapib (Fasted) | 14600 nanogram·hour/milliliter (ng·h/mL) | Geometric Coefficient of Variation 40 |
| Test (Fasted) | Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Evacetrapib (Fasted) | 14600 nanogram·hour/milliliter (ng·h/mL) | Geometric Coefficient of Variation 36 |
Primary
PK: Maximum Concentration (Cmax) of Evacetrapib (Fasted)
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 1,2,3, and 4
Population: All randomized participants who completed and had evaluable Cmax bioequivalence fasted state data for Periods 1,2,3 and 4.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference (Fasted) | PK: Maximum Concentration (Cmax) of Evacetrapib (Fasted) | 1130 nanogram/milliliter (ng/ml) | Geometric Coefficient of Variation 53 |
| Test (Fasted) | PK: Maximum Concentration (Cmax) of Evacetrapib (Fasted) | 1100 nanogram/milliliter (ng/ml) | Geometric Coefficient of Variation 40 |
Secondary
PK: AUC(0-∞)of Evacetrapib (Fasted and Fed)
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 2,4, and 5
Population: All randomized participants who completed and had evaluable AUC(0-∞) Fasted and Fed State data for Periods 2,4, and 5.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference (Fasted) | PK: AUC(0-∞)of Evacetrapib (Fasted and Fed) | 14800 ng·h/mL | Geometric Coefficient of Variation 39 |
| Test (Fasted) | PK: AUC(0-∞)of Evacetrapib (Fasted and Fed) | 18900 ng·h/mL | Geometric Coefficient of Variation 24 |
| Test (Fasted) | PK: AUC(0-∞)of Evacetrapib (Fasted and Fed) | 14600 ng·h/mL | Geometric Coefficient of Variation 39 |
| Test (Fed) | PK: AUC(0-∞)of Evacetrapib (Fasted and Fed) | 18600 ng·h/mL | Geometric Coefficient of Variation 26 |
Secondary
PK: Cmax of Evacetrapib (Fasted and Fed)
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 2,4, and 5
Population: All randomized participants who completed and had evaluable Cmax Fasted and Fed State data for Periods 2,4, and 5.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reference (Fasted) | PK: Cmax of Evacetrapib (Fasted and Fed) | 1100 ng/ml | Geometric Coefficient of Variation 57 |
| Test (Fasted) | PK: Cmax of Evacetrapib (Fasted and Fed) | 1450 ng/ml | Geometric Coefficient of Variation 21 |
| Test (Fasted) | PK: Cmax of Evacetrapib (Fasted and Fed) | 1090 ng/ml | Geometric Coefficient of Variation 44 |
| Test (Fed) | PK: Cmax of Evacetrapib (Fasted and Fed) | 1480 ng/ml | Geometric Coefficient of Variation 27 |
Secondary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib (Fasted and Fed)
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 Hours Post-dose in Periods 2,4, and 5
Population: All randomized participants who completed and had evaluable Tmax Fasted and Fed State data for Periods 2, 4, and 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reference (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib (Fasted and Fed) | 3.75 hour (h) |
| Test (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib (Fasted and Fed) | 2.50 hour (h) |
| Test (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib (Fasted and Fed) | 3.50 hour (h) |
| Test (Fed) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib (Fasted and Fed) | 2.75 hour (h) |