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

Phase 1

Completed

• Conditions: Neoplasm Metastasis
• Interventions: Drug: Drug Cocktail; Drug: Abemaciclib

• Registration Number: NCT02688088
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-02-17
• Study First Submitted QC: 2016-02-17
• Study First Posted: 2016-02-23
• Study Start: 2016-03-08
• Primary Completion: 2018-02-04
• Study Completion: 2021-01-06
• Status Verified: 2022-04-01
• Results First Submitted: 2022-04-01
• Results First Submitted QC: 2022-04-01
• Last Update Submitted: 2022-04-01
• Results First Posted: 2022-10-18
• Last Update Posted: 2022-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Drug Cocktail - Period 1	Drug Cocktail	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 + Drug Cocktail - Period 2	Drug Cocktail	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 + Drug Cocktail - Period 2	Abemaciclib	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 - Period 4	Abemaciclib	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 - Period 3	Abemaciclib	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.
Safety Extension Period	Abemaciclib	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin	Days 1 and 8: Predose, 0.5 1, 2, 3, 4, 6, 8, 12, 48, 72, 96 hr Postdose	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	Days 1 and 8: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72 hr postdose	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: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam	Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose	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.
Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine	Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose	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) of Midazolam	Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose	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	Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hr Postdose	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	Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hr Postdose	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	Days 1 and 8: 1, 2, 4, 6, 8, 10, 24, 48, 72 hr Postdose	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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1	Day 8: Baseline, 24 h postdose	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	Day 8: Baseline, 24 h postdose	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	Day 8: Baseline, 24 h postdose	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	Day 8: Baseline, 24 h postdose	Mean change from baseline in pulse rate at 24 h postdose following 200 mg abemaciclib and drug cocktail.

Trial Locations

Locations (5)

University of Kansas Hospital; 🇺🇸 Fairway, Kansas, United States

South Texas Accelerated Research Therapeutics, LCC; 🇺🇸 San Antonio, Texas, United States

Sarah Cannon Research Institute at HealthOne; 🇺🇸 Denver, Colorado, United States

IU Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Mary Crowley Cancer Research Center; 🇺🇸 Dallas, Texas, United States