A Study of Abemaciclib in Healthy Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Loperamide
Drug: Placebo
Drug: Abemaciclib

Registration Number: NCT02677844

Lead Sponsor: Eli Lilly and Company

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Loperamide	Loperamide	Cohort 2, only. 8 mg Loperamide given orally once in 1 of 4 study periods.
Placebo	Placebo	Single oral dose of placebo on Day 1 of 1 study period.
Loperamide + Placebo	Placebo	Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods.
Loperamide + Placebo	Loperamide	Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods.
Loperamide + Abemaciclib	Abemaciclib	Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods.
Loperamide + Abemaciclib	Loperamide	Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods.
Abemaciclib	Abemaciclib	200 - 600 mg single increasing oral dose of abemaciclib on Day 1 of up to 3 study periods.

Primary Outcome Measures

Name	Time	Method
Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF)	Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib	Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose	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.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide	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	Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide.
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide	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	Blood samples were collected from participants in Cohort 2 Period 4 (DDI) to determine plasma concentrations of Loperamide.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib	Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose	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.