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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis
• Intervention / Treatment: Drug: Drug Cocktail; Drug: Abemaciclib

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Simon Cancer Center
  • Kansas
    • Fairway, Kansas, United States, 66160
      • University of Kansas Hospital
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • San Antonio, Texas, United States, 78229-3307
      • South Texas Accelerated Research Therapeutics, LCC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Drug Cocktail - Period 1; 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; Administered orally; Other Names: Caffeine + Warfarin + Dextromethorphan + Midazolam
EXPERIMENTAL: 200 mg Abemaciclib + Drug Cocktail - Period 2; 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; Administered orally; Other Names: Caffeine + Warfarin + Dextromethorphan + Midazolam; Drug: Abemaciclib; Administered orally; Other Names: LY2835219
EXPERIMENTAL: 200 mg Abemaciclib - Period 3; 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; Administered orally; Other Names: LY2835219
EXPERIMENTAL: 200 mg Abemaciclib - Period 4; 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; Administered orally; Other Names: LY2835219
EXPERIMENTAL: Safety Extension Period; 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; Administered orally; Other Names: LY2835219

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 8, 2016
• Primary Completion (ACTUAL): February 4, 2018
• Study Completion (ACTUAL): January 6, 2021

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: February 17, 2016
• First Posted (ESTIMATE): February 23, 2016

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2022
• Last Update Submitted That Met QC Criteria: April 1, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Purinergic Antagonists; Purinergic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Respiratory System Agents; Anticoagulants; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Antitussive Agents; Midazolam; Dextromethorphan; Warfarin; Caffeine
• Other Study ID Numbers: 15537; I3Y-MC-JPCB (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO