A Study of Abemaciclib in Healthy Participants

Eli Lilly and Company35 enrolled

Overview

The purposes of this study are to determine: * The effect of single increasing doses of the study drug, abemaciclib, on healthy participants. * The relationship between the amount of abemaciclib and the electrical tracing of the heart rhythm when abemaciclib is given. * How much abemaciclib is found in the bloodstream and how long the body takes to get rid of it. Information about any side effects that occur will be collected. The study will enroll two groups (cohorts) of participants. Each group will complete 4 study periods. This study is expected to last about 3 months. Screening may occur up to 28 days prior to enrollment. All participants will undergo a follow-up assessment approximately 21 days after administration of their final dose of study drug.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Healthy

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Overtly healthy males or females, as determined by medical history and physical examination * Male participants will be sterile * Female participants must not be of childbearing potential Exclusion Criteria: * Have known allergies to abemaciclib, related compounds, or any components of the formulation * Have an abnormality in the 12-lead electrocardiogram (ECG) including a Fridericia's corrected QT interval (QTcF) greater than 450 milliseconds (ms) (males) or greater than 470 ms (females) * Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs * Have a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndromes, or constipation Additional Exclusion Criterion for Participants Enrolled in Cohort 2: * Have a known hypersensitivity to loperamide hydrochloride or to any of the excipients

Locations (2)

Covance Clinical Research Unit

Daytona Beach, Florida, United States

Covance Clinical Research Unit

Evansville, Indiana, United States

Outcomes

Primary Outcomes

Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF)

QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data. ECG monitoring was conducted using a 12-lead digital Holter recorder from approximately 2 hours predose through 24 hours postdose on Day 1 of each period using 12-lead digital Holter recorder. Fridericia-corrected QT interval (QTcF): QTcF = QT/RR1/3, where RR is the interval between two R waves.

Time frame: Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose

Secondary Outcomes

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

Blood samples were collected from participants in Cohort 1(all periods) and Cohort 2 (Periods 5, 6, and 7) to determine the plasma concentrations of Abemaciclib.

Time frame: Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib

Blood samples were collected from participants in Cohort 1(all periods) and Cohort 2 (Periods 5, 6, and 7) to determine the plasma concentrations of Abemaciclib 0-tlast.

Time frame: Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide

Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide.

Time frame: Day -3: Predose, 1, 2, 4, 6, 8, 12, 14, 24, and 48 hours postdose;Day 1 predose, (-0.25 hours), and Day1: 1, 2, 4, 6, 8, 10, 12, 14, 24, 48, and 72 hours Post Dose

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide

Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide.

Time frame: Day -3: Predose,1, 2, 4, 6, 8, 12, 14, 24, and 48 hours postdose;Day 1 predose, (-0.25 hours), and Day1: 1, 2, 4, 6, 8, 10, 12, 14, 24, 48, and 72 hours Post Dose