Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Central Nervous System Stimulants

All Drugs and Chemicals

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Anticoagulants

Analgesics

Antitussive Agents

Respiratory System Agents

Anti-Obesity Agents

Vasoconstrictor Agents

Other Dietary Supplements

Caffeine

Midazolam

Warfarin

Levomethorphan

Dextromethorphan

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Phenylpropanolamine

Guaifenesin

Chlorpheniramine, phenylpropanolamine drug combination

Excitatory Amino Acid Antagonists

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.

Drug Cocktail

Abemaciclib

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)

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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 in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 1.

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 in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 2, Day 1.

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 in pulse rate at 24 h postdose following 200 mg abemaciclib and drug cocktail.

Eli Lilly and Company

All participants who received at least one dose of study drug and have at least one postdose safety assessment.

As dose adjustments due to toxicity were allowed in Periods 2, 3, and 4, a participant may have entered Period 3 or 4 on a dose level other than 200 mg Abemaciclib. As a result, the number of participants for Periods 3 and 4 differ between the Participant Flow and the Adverse Events section.

Single dose of drug cocktail: 100 mg caffeine, 10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 1 in Period 1.

Drug Cocktail - Period 1

200 mg Abemaciclib administered orally every 12 hours (Q12H) on Days 1 to 12 in Period 2.

200 mg Abemaciclib - Period 2

200 mg Abemaciclib administered orally Q12H on Days 1 to 12 in Period 2. Single dose of drug cocktail: 100 mg caffeine, 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

200 mg Abemaciclib administered orally Q12H on Days 13 to 28 in Period 3, and Days 1 to 28 in Period 4.

200 mg Abemaciclib - Periods 3 and 4

200 mg Abemaciclib administered orally Q12H until discontinuation criteria are met.

Abemaciclib Safety Extension Period

A single dose of drug cocktail was administered on Day 1 of Period 1. Abemaciclib 200 mg was administered Q12H starting on Day 1 of Period 2 with coadministration of drug cocktail on Day 8. Participants continued to receive 200 mg abemaciclib (or modified dose as required) Q12H up to 16 days in Period 3 and up to 28 days in Period 4. Participants could participate in a safety extension phase in which they received 200 mg abemaciclib (or modified dose as required) Q12H until discontinuation criteria are met.

Overall

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

All participants who received at least one dose of drug cocktail.

Chief Medical Officer

Single oral dose of 100 mg caffeine administered orally on Day 1 in Period 1.

100 mg Caffeine

200 mg Abemaciclib administered orally Q12H on Days 1 to 12 in Period 2.

Single dose of drug cocktail: 100 mg caffeine, 10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 8.

Abemaciclib + 100 mg Caffeine

All participants who received at least one dose of study drug and had evaluable PK data.

Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine

10 mg warfarin administered orally on Day 1 in Period 1.

10 mg Warfarin

200 mg Abemaciclib + 10 mg Warfarin

Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin

30 mg dextromethorphan administered orally on Day 1 in Period 1.

30 mg Dextromethorphan

200 mg Abemaciclib administered orally Q12H on Days 1 to 12 in Period 2.

Single dose of drug cocktail: 100 mg caffeine, 10 mg warfarin, 30 mg dextromethorphan, and 0.2 mg midazolam administered orally on Day 8 in Period 2.

200 Abemaciclib + 30 mg Dextromethorphan

Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan

Single dose of 0.2 mg midazolam administered orally on Day 1 in Period 1.

0.2 mg Midazolam (Drug Cocktail)

200 mg Abemaciclib + 0.2 mg Midazolam

All subjects who received at least one dose of study drug and had evaluable PK data.

Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam

Single dose of 100 mg caffeine administered orally on Day of Period 1.

200 mg Abemaciclib + 100 mg Caffeine

Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine

Single dose 10 mg warfarin administered orally on Day of Period 1.

Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin

Single dose 30 mg administered orally on Day 1 of Period 1.

200 mg Abemaciclib + 30 mg Dextromethorphan

Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan

Single dose 0.2 mg midazolam administered orally on Day 1 of Period 1.

0.2 mg Midazolam

Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam

Systolic BP

Diastolic BP

Drug Cocktail Period 1

All subjects who received at least one dose of study drug and had at least one postdose safety assessment.

Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1

Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1

200 mg Abemaciclib administered orally Q12H on Days 1 to 12 in Period 2.

200 mg Abemaciclib

Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2

Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2

200 mg Abemaciclib + Drug Cocktail

200 mg Abemaciclib administered orally every 12 hours (Q12H) on Days 1 to 12 in Period 2.

Single dose of drug cocktail: 100 mg caffeine, 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.

.

200 mg Abemaciclib - Period 3

200 mg Abemaciclib administered orally Q12H on Days 1 to 28 in Period 4.

200 mg Abemaciclib Period - 4

200 mg Abemaciclib administered orally Q12H on Days 1 to 28 onwards in extension period.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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