Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to evaluate the effects of evacetrapib on oral contraceptives (Ortho-Cyclen®) when given to healthy female participants. The amount of female hormones found in the blood will be measured and compared when taken alone and when taken with evaceptrapib. Each woman will participate in two study periods. Information about any side effects that may occur will also be collected.
Interventions
DRUGOrtho-Cyclen
Oral administration
DRUGEvacetrapib
Oral administration
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Are pre-menopausal females, and who are healthy as determined by medical history and physical examination * Have a body mass index of 18 to 30 kilograms per square meter (kg/m\^2)
Exclusion criteria
* Have known allergies to evacetrapib and Ortho-Cyclen (ethinyl estradiol and norgestimate), related compounds or any components of the formulation * Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Have taken injectable contraceptives within 12 months prior to the first dose of the lead-in period or topical controlled delivery contraceptives (patch) for 3 months prior to the first dose of the lead-in period * Use of any tobacco- or nicotine-containing products within 6 months prior to the lead-in phase and during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Ethinyl Estradiol | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Minimum Observed Drug Concentration (Cmin) of Ethinyl Estradiol | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Ethinyl Estradiol | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Maximum Concentration (Cmax) of Norelgestromin | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Norelgestromin | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Minimum Observed Drug Concentration (Cmin) of Norelgestromin | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Norelgestromin | Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ortho-Cyclen and Ortho-Cyclen + Evacetrapib Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, QD for 28 days (lead-in period).
Treatment A Ortho-Cyclen administered orally, QD for 28 Days (Days 1 to 28) Treatment B Ortho-Cyclen orally, QD for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally, QD for 21 days (Days 1 to 21) | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Lead-In Period | Withdrawal by Subject | 1 | 0 | 0 |
| Period 1 | Physician Decision | 0 | 1 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 1 |
| Period 2 | Lost to Follow-up | 0 | 0 | 1 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Ortho-Cyclen and Ortho-Cyclen + Evacetrapib |
|---|---|
| Age, Continuous | 33.0 years STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 11 Participants |
| Region of Enrollment United States | 22 Participants |
| Sex/Gender, Customized Females | 22 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 | 9 / 22 | 5 / 17 | 5 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 17 | 0 / 21 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol | 71.7 picogram per milliliter (pg/ml) | Geometric Coefficient of Variation 35 |
| Ortho-Cyclen + Evacetrapib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol | 70.6 picogram per milliliter (pg/ml) | Geometric Coefficient of Variation 37 |
Primary
PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Ethinyl Estradiol
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen | PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Ethinyl Estradiol | 907 picogram x hour per ml (pg*hour/ml) | Geometric Coefficient of Variation 31 |
| Ortho-Cyclen + Evacetrapib | PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Ethinyl Estradiol | 840 picogram x hour per ml (pg*hour/ml) | Geometric Coefficient of Variation 28 |
Primary
PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Norelgestromin
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen | PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Norelgestromin | 16200 pg*hour/ml | Geometric Coefficient of Variation 21 |
| Ortho-Cyclen + Evacetrapib | PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Norelgestromin | 18100 pg*hour/ml | Geometric Coefficient of Variation 22 |
Primary
PK: Maximum Concentration (Cmax) of Norelgestromin
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen | PK: Maximum Concentration (Cmax) of Norelgestromin | 1410 pg/ml | Geometric Coefficient of Variation 21 |
| Ortho-Cyclen + Evacetrapib | PK: Maximum Concentration (Cmax) of Norelgestromin | 1830 pg/ml | Geometric Coefficient of Variation 17 |
Primary
PK: Minimum Observed Drug Concentration (Cmin) of Ethinyl Estradiol
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen | PK: Minimum Observed Drug Concentration (Cmin) of Ethinyl Estradiol | 15.9 pg/ml | Geometric Coefficient of Variation 65 |
| Ortho-Cyclen + Evacetrapib | PK: Minimum Observed Drug Concentration (Cmin) of Ethinyl Estradiol | 13.2 pg/ml | Geometric Coefficient of Variation 66 |
Primary
PK: Minimum Observed Drug Concentration (Cmin) of Norelgestromin
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ortho-Cyclen | PK: Minimum Observed Drug Concentration (Cmin) of Norelgestromin | 397 pg/ml | Geometric Coefficient of Variation 35 |
| Ortho-Cyclen + Evacetrapib | PK: Minimum Observed Drug Concentration (Cmin) of Norelgestromin | 422 pg/ml | Geometric Coefficient of Variation 34 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Ethinyl Estradiol
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ortho-Cyclen | PK: Time of Maximum Observed Drug Concentration (Tmax) of Ethinyl Estradiol | 3.00 hour |
| Ortho-Cyclen + Evacetrapib | PK: Time of Maximum Observed Drug Concentration (Tmax) of Ethinyl Estradiol | 4.00 hour |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Norelgestromin
Time frame: Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ortho-Cyclen | PK: Time of Maximum Observed Drug Concentration (Tmax) of Norelgestromin | 3.53 hour |
| Ortho-Cyclen + Evacetrapib | PK: Time of Maximum Observed Drug Concentration (Tmax) of Norelgestromin | 4.00 hour |