Clinical trial NCT02677844: A Study of Abemaciclib in Healthy Participants
Official title: A Randomized, Single-Blind, Placebo-Controlled, Single Ascending Dose Study to Determine the Exposure-Response Relationship Between Abemaciclib and QT Interval in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-02-09
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF)
timeFrame: Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
timeFrame: Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib
timeFrame: Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide
timeFrame: 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
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide
timeFrame: 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
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit
state: Florida
city: Evansville
country: United States
facility: Covance Clinical Research Unit
state: Indiana
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: