Clinical trial NCT02688088: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Metastasis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-02-23
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine
timeFrame: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose
measure: Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin
timeFrame: Days 1 and 8: Predose, 0.5 1, 2, 3, 4, 6, 8, 12, 48, 72, 96 hr Postdose
measure: Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan
timeFrame: Days 1 and 8: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72 hr postdose
measure: Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam
timeFrame: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine
timeFrame: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hr Postdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin
timeFrame: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hr Postdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan
timeFrame: Days 1 and 8: 1, 2, 4, 6, 8, 10, 24, 48, 72 hr Postdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam
timeFrame: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose
Secondary outcomes:
measure: Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1
timeFrame: Day 8: Baseline, 24 h postdose
measure: Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1
timeFrame: Day 8: Baseline, 24 h postdose
measure: Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2
timeFrame: Day 1: Baseline, 24 h postdose
measure: Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2
timeFrame: Day 1: Baseline, 24 h postdose
measure: Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2
timeFrame: Day 8: Baseline, 24 h postdose
measure: Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2
timeFrame: Day 8: Baseline, 24 h postdose
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthOne
state: Colorado
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LCC
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: