Neoplasm, Neoplasm Metastasis
Conditions
Keywords
advanced cancer, metastatic cancer
Brief summary
The purpose of this study is to assess how the body handles Abemaciclib when it is given with another drug called clarithromycin. The study doctor will measure the amount of Abemaciclib that is absorbed into the blood stream and the time that it takes to remove Abemaciclib from the body. The safety and tolerability of these drugs will be studied. Each participant will complete 2 study periods in fixed order. After screening, Period 1 will last approximately 8 days and Period 2 will last approximately 15 days. Participants who complete Period 2 may continue to receive Abemaciclib in 28-day cycles until discontinuation criteria are met.
Interventions
DRUGAbemaciclib
Administered orally
DRUGClarithromycin
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histological or cytological evidence of cancer (solid tumors) that is advanced and/or metastatic * Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
Exclusion criteria
* No symptomatic central nervous system (CNS) malignancy or metastasis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib | Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose |
| PK: Maximum Concentration (Cmax) of Abemaciclib | Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96,120,144,168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib Then Abemaciclib + Clarithromycin 50 mg single oral dose of Abemaciclib was administered on Period 1 Day 1 and on Period 2 Day 5. Clarithromycin 500 mg orally twice daily for 12 days. Clarithromycin dosing continued for 7 days following the single dose of Abemaciclib. After completing Period 2, eligible participants continued to receive 200 mg Abemaciclib Q12H on a 28-day cycle in a safety-extension phase until discontinuation criteria were met. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Abemaciclib Alone Period 1 | Adverse Event | 1 |
| Abemaciclib Alone Period 1 | Withdrawal by Subject | 1 |
| Abemaciclib + Clarithromycin Period 2 | Adverse Event | 1 |
| Abemaciclib + Clarithromycin Period 2 | Death | 1 |
| Abemaciclib + Clarithromycin Period 2 | Progressive Disease | 1 |
| Abemaciclib + Clarithromycin Period 2 | Withdrawal by Subject | 1 |
| Abemaciclib Safety-Extension Phase | Adverse Event | 2 |
| Abemaciclib Safety-Extension Phase | Death | 3 |
| Abemaciclib Safety-Extension Phase | Physician Decision | 1 |
| Abemaciclib Safety-Extension Phase | Progressive Disease | 12 |
| Abemaciclib Safety-Extension Phase | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Abemaciclib Then Abemaciclib + Clarithromycin |
|---|---|
| Age, Customized | 60.0 years STANDARD_DEVIATION 9.2 |
| Body Mass Index (BMI) | 27.62 kilogram/square meter (kg/m2) STANDARD_DEVIATION 6.04 |
| Eastern Cooperative Oncology Group (ECOG) Scale ECOG= 0 | 18 participants |
| Eastern Cooperative Oncology Group (ECOG) Scale ECOG= 1 | 8 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 25 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 19 Participants |
| Region of Enrollment United States | 26 Participants |
| Sex/Gender, Customized Female | 19 Participants |
| Sex/Gender, Customized Male | 7 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 | 13 / 26 | 7 / 24 | 10 / 21 | 19 / 20 |
| serious Total, serious adverse events | 1 / 26 | 1 / 24 | 1 / 21 | 15 / 20 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib
Time frame: Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose
Population: All participants who received at least 1 dose of study drug and had evaluable AUC(0-∞) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abemaciclib Period 1 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib | 2230 nanogram*hour/milliliter(mL) ng*h/mL | Geometric Coefficient of Variation 93 |
| Abemaciclib + Clarithromycin Period 2 | Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of Abemaciclib | 6850 nanogram*hour/milliliter(mL) ng*h/mL | Geometric Coefficient of Variation 66 |
Primary
PK: Maximum Concentration (Cmax) of Abemaciclib
Time frame: Period 1: Predose; 1, 2, 4, 6, 8, 10, 24, 48, 72, 96,120,144,168hr, Period 2: 1, 2, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240hr Post dose
Population: All participants who received at least 1 dose of study drug and had evaluable cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abemaciclib Period 1 | PK: Maximum Concentration (Cmax) of Abemaciclib | 70.0 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| Abemaciclib + Clarithromycin Period 2 | PK: Maximum Concentration (Cmax) of Abemaciclib | 84.3 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 55 |