Healthy
Conditions
Brief summary
This study will look at how a single dose of abemaciclib will impact the body's ability to get rid of two other drugs, metformin and iohexol. In addition, this study will evaluate the effect of a single dose of abemaciclib on kidney function by measuring blood and urine markers. Side effects will also be documented. Each participant will complete four study periods. During each study period, participants will stay in the clinical research unit for nine days and eight nights. The study will last approximately 10 weeks, not including screening. Screening is required within 28 days prior to the start of the study. This study is for research purposes only and is not intended to treat any medical condition.
Interventions
DRUGAbemaciclib
Administered orally
DRUGMetformin
Administered orally
DRUGIohexol
Administered intravenously (IV)
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
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) between 18 and 32 kilograms per meter squared (kg/m²), inclusive at screening
Exclusion criteria
* Have known allergies to abemaciclib, metformin, iodine, iohexol, 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 and/or positive antibodies of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin | Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) of Metformin was evaluated. |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin | Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin was evaluated. |
| Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin | Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose | Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol | Pre infusion, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 hours post infusion | Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol was evaluated. |
Countries
United States
Participant flow
Recruitment details
Participants were randomized to one of the four sequences and received either placebo or Abemaciclib along with Metformin or Iohexol. A washout period of at least 16 days following Abemaciclib administration & at least 5 days following placebo administration occurred between each period.
Pre-assignment details
Follow-up visit of 16 to 20 days occurred after administration of the last dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Single oral dose of placebo or 400 mg Abemaciclib is administered along with 1000 mg Metformin orally or 5 mL (3235 mg) Iohexol by IV infusion on day 1 as per the dosing schedule in each period. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-up Visit | Withdrawal by Subject | 1 | 0 | 0 | 1 |
| Period 1 | Dosing error | 2 | 2 | 0 | 0 |
| Period 2 | Adverse Event | 1 | 0 | 0 | 0 |
| Period 3 | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Period 4 | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Period 4 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Washout Period 1 | Lost to Follow-up | 0 | 1 | 0 | 1 |
| Washout Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Washout Period 3 | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Washout Period 3 | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 10.6 |
| Body Mass Index (BMI) | 27.25 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 18 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 | 19 Participants |
| Region of Enrollment United States | 40 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 33 | 11 / 35 | 0 / 32 | 6 / 33 |
| serious Total, serious adverse events | 0 / 33 | 0 / 35 | 0 / 32 | 0 / 33 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) of Metformin was evaluated.
Time frame: Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose
Population: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + 1000 mg Metformin | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin | 12100 Nanogram*Hour per Milliliter (ng*h/mL) | Geometric Coefficient of Variation 23 |
| 400 mg Abemaciclib + 1000 mg Metformin | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) of Metformin | 16800 Nanogram*Hour per Milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
Primary
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin was evaluated.
Time frame: Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose
Population: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + 1000 mg Metformin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin | 1550 ng/mL | Geometric Coefficient of Variation 23 |
| 400 mg Abemaciclib + 1000 mg Metformin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Metformin | 1940 ng/mL | Geometric Coefficient of Variation 31 |
Primary
Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin
Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin was evaluated.
Time frame: Pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36 hours (h) post dose
Population: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Metformin and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + 1000 mg Metformin | Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin | 21.5 Liters per Hour (L/h) | Geometric Coefficient of Variation 22 |
| 400 mg Abemaciclib + 1000 mg Metformin | Pharmacokinetics (PK): Renal Clearance (CLr) of Metformin | 11.9 Liters per Hour (L/h) | Geometric Coefficient of Variation 35 |
Secondary
Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol
Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol was evaluated.
Time frame: Pre infusion, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 hours post infusion
Population: All randomized participants who received at least one dose of study Abemaciclib or placebo along with Iohexol \& had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + 1000 mg Metformin | Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol | 89 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 17 |
| 400 mg Abemaciclib + 1000 mg Metformin | Pharmacokinetics (PK): Renal Clearance (CLr) of Iohexol | 85.6 Milliliter per minute (mL/min) | Geometric Coefficient of Variation 14 |