A Study of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body

Study Overview
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Brief Summary
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This study is known as a drug interaction study and is being done to see how abemaciclib may affect the blood levels of a drug mixture of commonly used drugs (caffeine, warfarin, dextromethorphan, and midazolam) when taken in combination with abemaciclib. Each participant will complete screening and four study periods in a fixed sequence, with the option to continue to receive abemaciclib in a safety extension phase. All participants will complete a safety follow-up.

Official Title
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Effects of Multiple Doses of Abemaciclib on the Pharmacokinetics of Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2D6, and CYP3A Substrates (Caffeine, Warfarin, Dextromethorphan, and Midazolam) in Cancer Patients

Conditions
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Neoplasm Metastasis

Intervention / Treatment
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* Drug: Drug Cocktail
* Drug: Abemaciclib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic Have adequate organ function Have a performance status of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, cancer-related hormone therapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug and have recovered from the acute effects of therapy(treatment related toxicity resolved to baseline), except for residual alopecia Exclusion Criteria: Require treatment with inducers or inhibitors of cytochrome P450 (CYP)1A2, CYP2C9, CYP2D6, and CYP3A within 14 days before the first dose of study drug through the end of Period 2 History or presence of significant bleeding disorders Have known active uncontrolled or symptomatic CNS metastases Have a primary liver tumor Have lymphoma or leukemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Drug Cocktail - Period 1<br>Single dose of drug cocktail: 100 milligram (mg) caffeine,10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 1 in Period 1. | Drug: Drug Cocktail<br>* Administered orally<br>* Other names: Caffeine + Warfarin + Dextromethorphan + Midazolam;|
| Experimental: 200 mg Abemaciclib + Drug Cocktail - Period 2<br>200 mg Abemaciclib administered orally every 12 hours (Q12H) on Days 1 - 12 in Period 2 with a single dose of drug cocktail: 100 mgcaffeine,10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 8 in Period 2. | Drug: Drug Cocktail<br>* Administered orally<br>* Other names: Caffeine + Warfarin + Dextromethorphan + Midazolam;Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|
| Experimental: 200 mg Abemaciclib - Period 3<br>200 mg Abemaciclib administered orally Q12H on Days 13 to 28 in Period 3. Participants may continue to receive abemaciclib until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|
| Experimental: 200 mg Abemaciclib - Period 4<br>200 mg Abemaciclib administered orally Q12H on Days 1 to 28 in Period 4. Participants may continue to receive abemaciclib until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|
| Experimental: Safety Extension Period<br>200 mg Abemaciclib administered orally Q12H on Days 1 to 28 onwards in extension period. Participants may continue to receive abemaciclib until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine | Maximum concentration of caffeine after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose | 
| Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin | Maximum concentration of S-warfarin after single dose of drug cocktail on Day 1 in Period 1and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 0.5 1, 2, 3, 4, 6, 8, 12, 48, 72, 96 hr Postdose | 
| Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan | Maximum concentration of dextromethorphan after single dose of drug cocktail on Day 1 of Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72 hr postdose | 
| Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam | Maximum concentration of midazolam after single dose of drug cocktail on Day 1 of Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose | 
| Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine | PK: AUC zero to infinity of caffeine after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hr Postdose | 
| Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin | AUC (zero to infinity) of S-warfarin after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hr Postdose | 
| Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan | PK: AUC (zero to infinity) of dextromethorphan after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: 1, 2, 4, 6, 8, 10, 24, 48, 72 hr Postdose | 
| Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam | PK: AUC (zero to infinity) of midazolam after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. | Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1 | Mean change from predose in systolic and diastolic blood pressure (BP) over 24 hours (h) postdose following single dose drug cocktail in Period 1. | Day 8: Baseline, 24 h postdose | 
| Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1 | Mean change from baseline in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 1. | Day 8: Baseline, 24 h postdose | 
| Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2 | Mean change from baseline in systolic and diastolic blood pressure (BP) over 24 hours (h) postdose following single dose of abemaciclib in Period 2, Day 1. | Day 1: Baseline, 24 h postdose | 
| Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2 | Mean change from baseline in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 2, Day 1. | Day 1: Baseline, 24 h postdose | 
| Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2 | Mean change from baseline in systolic and diastolic blood pressure (BP) at 24 h postdose following 200 mg abemaciclib and drug cocktail. | Day 8: Baseline, 24 h postdose | 
| Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2 | Mean change from baseline in pulse rate at 24 h postdose following 200 mg abemaciclib and drug cocktail. | Day 8: Baseline, 24 h postdose |