Healthy
Conditions
Brief summary
The purpose of this study is to evaluate the effect of lanabecestat on rosuvastatin. The amount of rosuvastatin in the blood will be compared, when taken alone, and then when taken with lanabecestat. The amount of lanabecestat that gets into the bloodstream will be measured. Information about any side effects that may occur will also be collected. Participants will be on study for 21 days with a follow-up at least 7 days afterwards. Screening will be undertaken within 45 days prior to enrollment.
Interventions
DRUGLanabecestat
Administered orally
DRUGRosuvastatin
Administered orally
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
NON_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
* Women not of childbearing potential may participate and include those who are: * Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis; or * Postmenopausal - defined as women over 50 years of age with an intact uterus who have not taken hormones or oral contraceptives within 1 year, who have had either Spontaneous cessation of menses for at least 12 consecutive months, or 6 to 12 months of spontaneous amenorrhea with follicle-stimulating hormone level greater than (\>)40 milli-international units per millilitre (mIU/mL) consistent with menopause * Caucasian and may be of Hispanic ethnicity * Body mass index (BMI) of 19 to 32 kilogram per meter square (kg/m²), inclusive, at the time of screening
Exclusion criteria
\- Have a clinically significant abnormal blood pressure or heart rate (supine) as determined by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve From Zero to Infinity (AUC-∞) of Rosuvastatin | 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose | Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve from Zero to Infinity (AUC-∞) of Rosuvastatin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814) | Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose | Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814) |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat | .Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat |
Countries
United States
Participant flow
Pre-assignment details
11 participants completed Period 1 but did not enter Period 2 because they did not meet the genotype criteria.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All participants who received at least 1 dose of study drug. | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 2 | Adverse Event | 2 |
| Period 2 | Physician Decision | 2 |
| Period 2 | Withdrawal by Subject | 1 |
| Washout | DId not meet genotype criteria | 11 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 45.2 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Genotype rsl045642 (ABCB1) Genotype A/A | 10 Participants |
| Genotype rsl045642 (ABCB1) Genotype A/G | 15 Participants |
| Genotype rsl045642 (ABCB1) Genotype G/G | 6 Participants |
| Genotype rsl045642 (ABCB1) Not performed | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 42 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 29 | 0 / 26 |
| other Total, other adverse events | 0 / 42 | 2 / 29 | 3 / 26 |
| serious Total, serious adverse events | 0 / 42 | 0 / 29 | 0 / 26 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve From Zero to Infinity (AUC-∞) of Rosuvastatin
Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve from Zero to Infinity (AUC-∞) of Rosuvastatin
Time frame: 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose
Population: All participants who received at least 1 dose of study drug, had evaluable PK parameters. Period 2 stand alone lanabecestat PK was not performed so only 2 arms are presented that is the data in totality.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve From Zero to Infinity (AUC-∞) of Rosuvastatin | 80 hours times nanogram per milliliter | Geometric Coefficient of Variation 47 |
| Rosuvastatin + Lanabecestat (LY3314814) | Pharmacokinetics (PK): Area Under The Drug Concentration Time Curve From Zero to Infinity (AUC-∞) of Rosuvastatin | 78 hours times nanogram per milliliter | Geometric Coefficient of Variation 56 |
Secondary
Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814)
Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814)
Time frame: Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose
Population: All participants who received at least 1 dose of study drug, had evaluable PK parameters. Period 2 stand alone lanabecestat PK was not performed so only 2 arms are presented that is the data in totality.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814) | 3650 hours times nanograms per milliliter | Geometric Coefficient of Variation 25 |
| Rosuvastatin + Lanabecestat (LY3314814) | Pharmacokinetics (PK): Area Under the Drug Concentration Time Curve During a 24-hour Dosing Interval (AUCτ) of Lanabecestat (LY3314814) | 3790 hours times nanograms per milliliter | Geometric Coefficient of Variation 21 |
Secondary
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat
Time frame: .Period 2 (Day 7, 8): Predose, 0.5, 1, 2, 3, 4, 8, 12 hours postdose
Population: All participants who received at least 1 dose of study drug and had evaluable PK data. Period 2 stand alone lanabecestat PK was not performed so only 2 arms are presented that is the data in totality.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat | 369 nanograms per milliliter | Geometric Coefficient of Variation 27 |
| Rosuvastatin + Lanabecestat (LY3314814) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lanabecestat | 399 nanograms per milliliter | Geometric Coefficient of Variation 20 |