Healthy Volunteers
Conditions
Brief summary
The main purpose of this study is to determine how much digoxin gets into the blood stream and how long it takes the body to get rid of it when given with the study drug evacetrapib. This study will also look at the effect of evacetrapib on the removal of digoxin from the body by the kidneys. Information about any side effects that may occur will be collected. This study will last approximately 33 days for each participant, not including screening.
Interventions
DRUGDigoxin
Administered orally
DRUGEvacetrapib
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males and females (of non-childbearing potential) * Have a body mass index of 18 to 32 kilograms per square meter (kg/m\^2) * Normal renal function
Exclusion criteria
* Participants who currently smoke or use tobacco or nicotine products
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Digoxin | Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of Digoxin | Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin | Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Clearance (CLr) of Digoxin | Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin | CLr was defined as the volume of serum cleared of digoxin per unit of time after a single dose of digoxin. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Evacetrapib+Digoxin Period 1 (Day 1 through Day 6 Predose): Participants received a single oral dose of 0.5 mg digoxin on Day 1 Period 2 (Day 6 Post-Dose through Day 20): Participants received an oral dose of 130 mg evacetrapib QD on Days 6 through 19 with a single oral dose of 0.5 mg digoxin administered on Day 15 | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 (Day 1 Through Day 6 Predose) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Evacetrapib+Digoxin |
|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 16 | 1 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Digoxin
Time frame: Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin
Population: All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1-Digoxin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Digoxin | 1.75 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| Period 2-Evacetrapib + Digoxin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Digoxin | 2.15 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
Primary
PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of Digoxin
Time frame: Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin
Population: All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable AUC0-∞ data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1-Digoxin | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of Digoxin | 31.3 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 18 |
| Period 2-Evacetrapib + Digoxin | PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of Digoxin | 33.5 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin
Time frame: Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin
Population: All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable tmax data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1-Digoxin | PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin | 2.00 hours |
| Period 2-Evacetrapib + Digoxin | PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin | 2.00 hours |
Secondary
Renal Clearance (CLr) of Digoxin
CLr was defined as the volume of serum cleared of digoxin per unit of time after a single dose of digoxin.
Time frame: Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin
Population: All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable CLr data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1-Digoxin | Renal Clearance (CLr) of Digoxin | 9.43 liters/hour (L/h) | Geometric Coefficient of Variation 14 |
| Period 2-Evacetrapib + Digoxin | Renal Clearance (CLr) of Digoxin | 8.10 liters/hour (L/h) | Geometric Coefficient of Variation 18 |