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

Primary Purpose

Neoplasm Metastasis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Drug Cocktail
Abemaciclib
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Neoplasm Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sarah Cannon Research Institute at HealthOne
  • IU Simon Cancer Center
  • University of Kansas Hospital
  • Mary Crowley Cancer Research Center
  • South Texas Accelerated Research Therapeutics, LCC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Drug Cocktail - Period 1

200 mg Abemaciclib + Drug Cocktail - Period 2

200 mg Abemaciclib - Period 3

200 mg Abemaciclib - Period 4

Safety Extension Period

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
February 17, 2016
Last Updated
April 1, 2022
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT02688088
Brief Title
A Study of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 1, 2022
Overall Recruitment Status
Completed
Study Start Date
March 8, 2016 (Actual)
Primary Completion Date
February 4, 2018 (Actual)
Study Completion Date
January 6, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm Metastasis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Drug Cocktail - Period 1
Arm Type
Active Comparator
Arm Description
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.
Arm Title
200 mg Abemaciclib + Drug Cocktail - Period 2
Arm Type
Experimental
Arm Description
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.
Arm Title
200 mg Abemaciclib - Period 3
Arm Type
Experimental
Arm Description
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.
Arm Title
200 mg Abemaciclib - Period 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Safety Extension Period
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Drug Cocktail
Other Intervention Name(s)
Caffeine + Warfarin + Dextromethorphan + Midazolam
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Other Intervention Name(s)
LY2835219
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine
Description
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.
Time Frame
Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose
Title
Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin
Description
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.
Time Frame
Days 1 and 8: Predose, 0.5 1, 2, 3, 4, 6, 8, 12, 48, 72, 96 hr Postdose
Title
Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan
Description
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.
Time Frame
Days 1 and 8: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72 hr postdose
Title
Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam
Description
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.
Time Frame
Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose
Title
Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine
Description
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.
Time Frame
Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hr Postdose
Title
Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin
Description
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.
Time Frame
Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hr Postdose
Title
Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan
Description
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.
Time Frame
Days 1 and 8: 1, 2, 4, 6, 8, 10, 24, 48, 72 hr Postdose
Title
Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam
Description
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.
Time Frame
Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose
Secondary Outcome Measure Information:
Title
Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1
Description
Mean change from predose in systolic and diastolic blood pressure (BP) over 24 hours (h) postdose following single dose drug cocktail in Period 1.
Time Frame
Day 8: Baseline, 24 h postdose
Title
Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1
Description
Mean change from baseline in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 1.
Time Frame
Day 8: Baseline, 24 h postdose
Title
Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2
Description
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.
Time Frame
Day 1: Baseline, 24 h postdose
Title
Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2
Description
Mean change from baseline in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 2, Day 1.
Time Frame
Day 1: Baseline, 24 h postdose
Title
Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2
Description
Mean change from baseline in systolic and diastolic blood pressure (BP) at 24 h postdose following 200 mg abemaciclib and drug cocktail.
Time Frame
Day 8: Baseline, 24 h postdose
Title
Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2
Description
Mean change from baseline in pulse rate at 24 h postdose following 200 mg abemaciclib and drug cocktail.
Time Frame
Day 8: Baseline, 24 h postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Sarah Cannon Research Institute at HealthOne
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
IU Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Hospital
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Mary Crowley Cancer Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
South Texas Accelerated Research Therapeutics, LCC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3307
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/6XBlVQ9rvUSAoYsMwsICsu
Description
A Study of Abemaciclib in Participants With Cancer That is Advanced or Has Spread to Another Part(s) of the Body

Learn more about this trial

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

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