NCT02677844

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P50-P75 for phase_1 healthy

Timeline
Completed

Started Feb 2016

Typical duration for phase_1 healthy

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2016

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

February 5, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 9, 2016

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

August 3, 2018

Completed
Last Updated

January 4, 2019

Status Verified

December 1, 2018

Enrollment Period

5 months

First QC Date

February 5, 2016

Results QC Date

October 27, 2017

Last Update Submit

December 13, 2018

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • 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

  • 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

Study Arms (5)

Abemaciclib

EXPERIMENTAL

200 - 600 mg single increasing oral dose of abemaciclib on Day 1 of up to 3 study periods.

Drug: Abemaciclib

Placebo

PLACEBO COMPARATOR

Single oral dose of placebo on Day 1 of 1 study period.

Drug: Placebo

Loperamide

ACTIVE COMPARATOR

Cohort 2, only. 8 mg Loperamide given orally once in 1 of 4 study periods.

Drug: Loperamide

Loperamide + Abemaciclib

EXPERIMENTAL

Cohort 2, only. 8 mg Loperamide co-administered with abemaciclib given orally once in up to 1 of 4 study periods.

Drug: AbemaciclibDrug: Loperamide

Loperamide + Placebo

ACTIVE COMPARATOR

Cohort 2, only. 8 mg Loperamide co-administered with placebo given orally once in up to 1 of 4 study periods.

Drug: PlaceboDrug: Loperamide

Interventions

AbemaciclibDRUG

Administered orally

Also known as: LY2835219
AbemaciclibLoperamide + Abemaciclib
PlaceboDRUG

Administered orally

Loperamide + PlaceboPlacebo
LoperamideDRUG

Administered orally

LoperamideLoperamide + AbemaciclibLoperamide + Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • Have a known hypersensitivity to loperamide hydrochloride or to any of the excipients

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Covance Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

Covance Clinical Research Unit

Evansville, Indiana, 47710, United States

Location

MeSH Terms

Interventions

abemaciclibLoperamide

Intervention Hierarchy (Ancestors)

PiperidinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

At the 600-mg dose level, the protocol-specified dose escalation stopping criteria had been met so no participants received the 900-mg dose in this study.

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company
800-545-5979

Study Officials

  • 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)

    Eli Lilly and Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

February 5, 2016

First Posted

February 9, 2016

Study Start

February 1, 2016

Primary Completion

July 1, 2016

Study Completion

July 1, 2016

Last Updated

January 4, 2019

Results First Posted

August 3, 2018

Record last verified: 2018-12

Locations

US(2)