A Study of Abemaciclib in Healthy Participants

A Randomized, Single-Blind, Placebo-Controlled, Single Ascending Dose Study to Determine the Exposure-Response Relationship Between Abemaciclib and QT Interval in Healthy Subjects

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 Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Abemaciclib; Drug: Loperamide

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Unit
  • Indiana
    • Evansville, Indiana, United States, 47710
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abemaciclib; 200 - 600 mg single increasing oral dose of abemaciclib on Day 1 of up to 3 study periods.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219
Placebo Comparator: Placebo; Single oral dose of placebo on Day 1 of 1 study period.	Drug: Placebo; Administered orally
Active Comparator: Loperamide; Cohort 2, only. 8 mg Loperamide given orally once in 1 of 4 study periods.	Drug: Loperamide; Administered orally
Experimental: Loperamide + Abemaciclib; Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods.	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Loperamide; Administered orally
Active Comparator: Loperamide + Placebo; Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods.	Drug: Placebo; Administered orally; Drug: Loperamide; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 9, 2016

Study Record Updates

• Last Update Posted (Actual): January 4, 2019
• Last Update Submitted That Met QC Criteria: December 13, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Agents; Loperamide; Antidiarrheals
• Other Study ID Numbers: 16080; I3Y-MC-JPCA (Other Identifier: Eli Lilly and Company)