Healthy
Conditions
Brief summary
The purpose of this study is to measure how much abemaciclib gets into the blood stream and how long it takes the body to get rid of it when given as capsules versus a tablet(s). The effect of a high fat meal on the tablet formulation will also be evaluated. In addition, the tolerability of abemaciclib tablet and capsule formulations will be evaluated. Information about any side effects that may occur will also be collected. This study has 3 parts. Parts A and C will last about 44 days including follow-up. Part B will last about 60 days including follow-up. Screening may occur up to 28 days before the first dose of study drug. Participants are only allowed to enroll in one part. This study is for research purposes only and is not intended to treat any medical condition.
Interventions
DRUGAbemaciclib Capsules (Reference Formulation)
Administered orally
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
* Healthy surgically sterile or postmenopausal females and sterile males * Have a body mass index (BMI) 18 to 32 kilograms per square meter (kg/m²)
Exclusion criteria
* Have known allergies to abemaciclib, related compounds, or any components of the formulation * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Show evidence of hepatitis C and/or positive hepatitis C antibody * Show evidence of hepatitis B and/or positive hepatitis B surface antigen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Parts A and C Periods 1 and 2; Part B Periods 1, 2, 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 96, 120,144,168 and 192 hours postdose | Area under the concentration versus time curve from zero to infinity. |
| PK: Maximum Observed Drug Concentration (Cmax) | Parts A and C Periods 1 and 2; Part B Periods 1, 2, 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 96, 120,144,168 and 192 hours postdose | Maximum observed drug concentration. |
Countries
United States
Participant flow
Pre-assignment details
A 2- and 3-period crossover study conducted in 3 parts, with Part A followed by Parts B and C. Participants received single oral doses of abemaciclib on 2 separate occasions in Parts A and C and on 3 separate occasions in Part B.There was a washout interval of at least 16 days between periods.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Abemaciclib Reference formulation (R) = 3 x 50 mg abemaciclib capsules, Test formulation (T150) = 150 mg abemaciclib tablet administered orally on Day 1 in each of 2 periods. | 14 |
| Part B Abemaciclib R = 3 x 50 mg abemaciclib capsules, T150 = 150 mg abemaciclib tablet, Test Formulation 50 (T50) = 3 x 50 mg abemaciclib tablets administered orally on Day 1 in each of 3 periods. | 89 |
| Part C Abemaciclib T150 Fed and T150 Fasted = 150 mg abemaciclib tablet with a high-fat meal (T150 Fed) and then without a high-fat meal (T150 Fasted) on Day 1 in each of 2 periods administered orally. | 24 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 3 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Period 3 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: Abemaciclib | Total | Part C Abemaciclib | Part B Abemaciclib |
|---|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 16.9 | 52.7 years STANDARD_DEVIATION 12 | 55.5 years STANDARD_DEVIATION 10.6 | 51.8 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 38 Participants | 10 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 89 Participants | 14 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 16 Participants | 0 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 9 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 100 Participants | 22 Participants | 69 Participants |
| Region of Enrollment United States | 14 Participants | 127 Participants | 24 Participants | 89 Participants |
| Sex: Female, Male Female | 11 Participants | 110 Participants | 21 Participants | 78 Participants |
| Sex: Female, Male Male | 3 Participants | 17 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 14 | 6 / 14 | 21 / 88 | 17 / 87 | 22 / 88 | 3 / 24 | 1 / 24 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 88 | 0 / 87 | 0 / 88 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])
Area under the concentration versus time curve from zero to infinity.
Time frame: Parts A and C Periods 1 and 2; Part B Periods 1, 2, 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 96, 120,144,168 and 192 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 150 mg Abemaciclib (T150) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 3080 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 57 |
| Part A: 3 x 50 mg Abemaciclib (R) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 2880 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 56 |
| Part B: 150 mg Abemaciclib (T150) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 3110 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 55 |
| Part B: 3 x 50 mg Abemaciclib (T50) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 3120 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
| Part B: 3 x 50 mg Abemaciclib (R) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 3130 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 59 |
| Part C: 150 mg Abemaciclib (Fed) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 4170 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 49 |
| Part C: 150 mg Abemaciclib (Fasted) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 3590 Nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 45 |
Primary
PK: Maximum Observed Drug Concentration (Cmax)
Maximum observed drug concentration.
Time frame: Parts A and C Periods 1 and 2; Part B Periods 1, 2, 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 96, 120,144,168 and 192 hours postdose
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 150 mg Abemaciclib (T150) | PK: Maximum Observed Drug Concentration (Cmax) | 104 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
| Part A: 3 x 50 mg Abemaciclib (R) | PK: Maximum Observed Drug Concentration (Cmax) | 101 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Part B: 150 mg Abemaciclib (T150) | PK: Maximum Observed Drug Concentration (Cmax) | 95.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| Part B: 3 x 50 mg Abemaciclib (T50) | PK: Maximum Observed Drug Concentration (Cmax) | 97.7 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| Part B: 3 x 50 mg Abemaciclib (R) | PK: Maximum Observed Drug Concentration (Cmax) | 95.8 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| Part C: 150 mg Abemaciclib (Fed) | PK: Maximum Observed Drug Concentration (Cmax) | 130 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
| Part C: 150 mg Abemaciclib (Fasted) | PK: Maximum Observed Drug Concentration (Cmax) | 99.6 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |