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

Neoplasm Metastasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02688088
• Other study ID #: 15537
• Secondary ID: I3Y-MC-JPCB
• Status: Completed
• Phase: Phase 1
• Start date: March 8, 2016
• Est. completion date: January 6, 2021

Study information

• Verified date: April 1, 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: January 6, 2021
• Est. primary completion date: February 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Drug:
• Drug Cocktail
Administered orally
• Abemaciclib
Administered orally

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Sarah Cannon Research Institute at HealthOne	Denver	Colorado
United States	University of Kansas Hospital	Fairway	Kansas
United States	IU Simon Cancer Center	Indianapolis	Indiana
United States	South Texas Accelerated Research Therapeutics, LCC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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