A Randomized, Single-Blind, Placebo-Controlled, Single Ascending Dose Study to Determine the Exposure-Response Relationship Between Abemaciclib and QT Interval in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Abemaciclib
- Conditions
- Healthy
- Sponsor
- Eli Lilly and Company
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
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
Arms & Interventions
Abemaciclib
200 - 600 mg single increasing oral dose of abemaciclib on Day 1 of up to 3 study periods.
Intervention: Abemaciclib
Placebo
Single oral dose of placebo on Day 1 of 1 study period.
Intervention: Placebo
Loperamide
Cohort 2, only. 8 mg Loperamide given orally once in 1 of 4 study periods.
Intervention: Loperamide
Loperamide + Abemaciclib
Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods.
Intervention: Abemaciclib
Loperamide + Abemaciclib
Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods.
Intervention: Loperamide
Loperamide + Placebo
Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods.
Intervention: Placebo
Loperamide + Placebo
Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods.
Intervention: Loperamide
Outcomes
Primary Outcomes
Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF)
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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)