Healthy
Conditions
Brief summary
The purpose of this study is to evaluate the amount of abemaciclib that reaches the blood stream and how long the body takes to get rid of it when given with and without food. In addition, the safety and tolerability of the study drug will be evaluated. Information about any side effects that may occur will also be collected. The study will last about 43 days for each participant, not including screening.
Interventions
DRUGAbemaciclib
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 No maximum
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy sterile males or surgically sterile or postmenopausal females * Have a body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m\^2), inclusive
Exclusion criteria
* Participated in a clinical trial involving investigational product within 30 days * Have known allergies to abemaciclib, related compounds or any components of the formulation, or history of significant atopy * 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 blood pressure * Show evidence of human immunodeficiency virus (HIV), hepatitis B or hepatitis C * Have donated blood of more than 500 milliliter (mL) within the last month * Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to stop alcohol consumption 48 hours prior to each admission until collection of the last PK sample in each period * Are unwilling to refrain from consuming xanthine-containing food and drink from 48 hours prior to admission until collection of the last pharmacokinetic (PK) sample in each period * Are currently or have been smokers or users of tobacco or nicotine replacement products within the 6 months prior to admission or have a positive urine cotinine test * Are unwilling to comply with the dietary requirements/restrictions during the study: Consume only the meals provided during the inpatient stays and refrain from eating any food or drinking any beverages containing grapefruit, grapefruit juice, grapefruit-containing products, Seville oranges, star fruit or star fruit juice, pomelo, or commercial apple juice or orange juice for at least 2 weeks prior to the first dose until the final PK sample is collected
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose in Each Period |
| Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose in Each Period |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose in Each Period |
Countries
United States
Participant flow
Pre-assignment details
In this two-period crossover study, abemaciclib was administered once (fasting or fed) in each period. There were at least 16 days between doses and follow-up was completed 15 to 18 days after the last dose in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib 200 mg abemaciclib administered once orally in each of two study periods. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Abemaciclib |
|---|---|
| Age, Continuous | 49.1 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 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 | 7 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 | 22 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 30 | 2 / 29 |
| serious Total, serious adverse events | 0 / 30 | 0 / 29 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose in Each Period
Population: All participants who received abemaciclib and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib Fasted | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Abemaciclib | 3940 nanograms x hours/mililiters (ng·h/mL) | Geometric Coefficient of Variation 34 |
| Abemaciclib Fasted | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN2839567 | 1630 nanograms x hours/mililiters (ng·h/mL) | Geometric Coefficient of Variation 27 |
| Abemaciclib Fasted | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN3106726 | 3180 nanograms x hours/mililiters (ng·h/mL) | Geometric Coefficient of Variation 25 |
| Abemaciclib Fed | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Abemaciclib | 4950 nanograms x hours/mililiters (ng·h/mL) | Geometric Coefficient of Variation 42 |
| Abemaciclib Fed | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN2839567 | 1910 nanograms x hours/mililiters (ng·h/mL) | Geometric Coefficient of Variation 28 |
| Abemaciclib Fed | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN3106726 | 3410 nanograms x hours/mililiters (ng·h/mL) | Geometric Coefficient of Variation 28 |
Primary
Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose in Each Period
Population: All participants who received abemaciclib and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib Fasted | Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Abemaciclib | 116 ng/mL | Geometric Coefficient of Variation 36 |
| Abemaciclib Fasted | Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN2839567 | 33.4 ng/mL | Geometric Coefficient of Variation 36 |
| Abemaciclib Fasted | Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN3106726 | 55.7 ng/mL | Geometric Coefficient of Variation 31 |
| Abemaciclib Fed | Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Abemaciclib | 159 ng/mL | Geometric Coefficient of Variation 38 |
| Abemaciclib Fed | Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN2839567 | 41.4 ng/mL | Geometric Coefficient of Variation 29 |
| Abemaciclib Fed | Pharmacokinetics: Maximum Concentration (Cmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN3106726 | 61.0 ng/mL | Geometric Coefficient of Variation 29 |
Secondary
Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites
Time frame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose in Each Period
Population: All participants who received abemaciclib and had evaluable plasma values.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Abemaciclib Fasted | Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Abemaciclib | 8.00 hours |
| Abemaciclib Fasted | Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN2839567 | 6.00 hours |
| Abemaciclib Fasted | Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN3106726 | 8.02 hours |
| Abemaciclib Fed | Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | Abemaciclib | 8.00 hours |
| Abemaciclib Fed | Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN2839567 | 6.00 hours |
| Abemaciclib Fed | Pharmacokinetics: Time to Maximum Concentration (Tmax) for Both Fed and Fasted Periods for Abemaciclib and Major Metabolites | LSN3106726 | 10.00 hours |