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CompletedNCT02677844Updated Jan 4, 2019Results posted

A Study of Abemaciclib in Healthy Participants

A Phase 1 interventional study of Abemaciclib and Placebo in Healthy, sponsored by Eli Lilly and Company. Completed at 2 sites in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-01-04.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
35
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Healthy
03

In context

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Single (Participant)
Enrollment
35 participants (actual)

Study arms

  • Experimental
    Abemaciclib

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

    Drug: Abemaciclib

  • Placebo comparator
    Placebo

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

    Drug: Placebo

  • Active comparator
    Loperamide

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

    Drug: Loperamide

  • 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 · Drug: Loperamide

  • 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 · Drug: Loperamide

Interventions

  • DrugAbemaciclib

    Administered orally

    Also known as: LY2835219

  • DrugPlacebo

    Administered orally

  • DrugLoperamide

    Administered orally

06

What researchers measure

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.

    Time frame: Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose

Secondary outcomes

  1. 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.

    Time frame: Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose

  2. 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.

    Time frame: Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose

  3. 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.

    Time frame: 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

  4. 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.

    Time frame: 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

07

Results

Posted Aug 3, 2018
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.

Participant flow

Dose escalation study with 2 cohorts, participants in cohort 1 were randomized to 1 of 4 sequences \& participants in cohort 2 were randomized to 1 of 3 sequences. Cohort 1 had periods 1 to 4 with at least 5 days washout between each dose, Cohort 2 had periods 4(DDI) to 7 with at least 8 days washout between each dose.

Period 1
Participant flow — Period 1
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started5555000
Completed5555000
Not completed0000000
Period 2
Participant flow — Period 2
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started5555000
Completed5555000
Not completed0000000
Period 3
Participant flow — Period 3
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started5555000
Completed5554000
Not completed0001000
Withdrew: Withdrawal by subject0001000
Period 4
Participant flow — Period 4
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started5554000
Completed5554000
Not completed0000000
Period 4 (DDI)
Participant flow — Period 4 (DDI)
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started0000744
Completed0000744
Not completed0000000
Period 5
Participant flow — Period 5
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started0000744
Completed0000744
Not completed0000000
Period 6
Participant flow — Period 6
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started0000744
Completed0000744
Not completed0000000
Period 7
Participant flow — Period 7
MilestoneCohort 1 Sequence 1Cohort 1 Sequence 2Cohort 1 Sequence 3Cohort 1 Sequence 4Cohort 2 Sequence 1Cohort 2 Sequence 2Cohort 2 Sequence 3
Started0000744
Completed0000744
Not completed0000000

Outcome measures

PrimaryMean 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.

Time frame:
Day 1: 2hr,4hr,6hr,8hr,10hr,12hr,14hr,24hr Post Dose
Reported as:
Mean · Millisecond (msec)
Mean Time Matched Placebo-Adjusted Changes From Baseline For Fridericia's Corrected QT Interval (ΔΔQTcF)
Millisecond (msec)200 mg Abemaciclib300 mg Abemaciclib400 mg Abemaciclib600 mg Abemaciclib
2hr1.4 (-0.4 to 4.8)3.3 (-2.1 to 4.3)0.2 (-3.7 to 1.3)-2.1 (-7.3 to 0.6)
4hr-2.0 (-5.1 to 1.6)0.8 (-4.5 to 0.8)-0.7 (-4.9 to 0.6)-4.2 (-9.9 to 0.9)
6hr0.6 (-1.5 to 5.2)-0.2 (-5.8 to 1.2)-1.8 (-5.9 to -0.1)-3.7 (-10.3 to -0.8)
8hr2.8 (0.7 to 6.4)2.7 (-3.1 to 4.0)2.2 (-1.8 to 3.5)2.8 (-3.9 to 5.8)
10hr2.1 (0.6 to 5.1)1.3 (-3.7 to 1.7)1.5 (-2.4 to 2.1)5.9 (-2.8 to 11)
12hr-0.3 (-4.7 to 5.6)-0.7 (-6.6 to 0.8)-0.5 (-4.4 to 0.1)4.4 (-0.9 to 7.2)
14hr3.9 (1.4 to 7.9)3.3 (-2.1 to 4.1)1.0 (-3.9 to 2.6)2.3 (-4.4 to 5.4)
24hr1.4 (-1.2 to 5.5)4.2 (-0.7 to 4.8)-0.4 (-4.7 to 1.3)0.9 (-7.1 to 4.6)
SecondaryPharmacokinetics (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.

Time frame:
Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose
Reported as:
Geometric mean · Nanogram per Milliliter (ng/mL)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
Nanogram per Milliliter (ng/mL)200 mg Abemaciclib300 mg Abemaciclib400 mg Abemaciclib600 mg Abemaciclib400 mg Abemaciclib + Loperamide 8mg
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib102 ± 31130 ± 40182 ± 42308 ± 45199 ± 55
SecondaryPharmacokinetics (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.

Time frame:
Day 1: 2, 4, 6, 8, 10, 12, 14, 24, 48, 72, 96, and 120 hours Post Dose
Reported as:
Geometric mean · ng*hr/mL
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib
ng*hr/mL200 mg Abemaciclib300 mg Abemaciclib400 mg Abemaciclib600 mg Abemaciclib400 mg Abemaciclib + 8 mg Loperamide
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time 0 to Last Time Point With Measurable Concentration AUC(0-tlast) of Abemaciclib3560 ± 385210 ± 377610 ± 4614600 ± 429420 ± 57
SecondaryPharmacokinetics (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.

Time frame:
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
Reported as:
Geometric mean · ng*hr/mL
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide
ng*hr/mL8 mg Loperamide8 mg Loperamide + 400 mg Abemaciclib
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Last Time Point With Measurable Concentration [AUC(0-tlast)] of Loperamide46.1 ± 4747.3 ± 53
SecondaryPharmacokinetics (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.

Time frame:
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
Reported as:
Geometric mean · ng/mL
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide
ng/mL8 mg Loperamide8 mg Loperamide + 400 mg Abemaciclib
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Loperamide1.83 ± 562.17 ± 49

Adverse events

Collected over Up to 117 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—0/34 (0%)9/34 (26.5%)
200 mg Abemaciclib—0/20 (0%)4/20 (20%)
300 mg Abemaciclib—0/20 (0%)5/20 (25%)
400 mg Abemaciclib—0/35 (0%)17/35 (48.6%)
600 mg Abemaciclib—0/15 (0%)12/15 (80%)
8 mg Loperamide—0/15 (0%)5/15 (33.3%)
8 mg Loperamide + Placebo—0/7 (0%)3/7 (42.9%)
8 mg Loperamide + 400 mg Abemaciclib—0/8 (0%)3/8 (37.5%)
Most frequent other events
Showing 10 of 28
Most frequent other events
EventPlacebo200 mg Abemaciclib300 mg Abemaciclib400 mg Abemaciclib600 mg Abemaciclib8 mg Loperamide8 mg Loperamide + Placebo8 mg Loperamide + 400 mg Abemaciclib
DiarrhoeaGastrointestinal disorders3/341/204/2011/3511/150/150/71/8
NauseaGastrointestinal disorders0/343/200/206/358/150/151/72/8
VomitingGastrointestinal disorders1/341/200/202/356/150/150/71/8
ConstipationGastrointestinal disorders0/340/200/200/350/152/152/70/8
Alanine aminotransferase increasedInvestigations0/340/200/200/350/150/152/72/8
Aspartate aminotransferase increasedInvestigations0/340/200/200/350/150/152/72/8
HeadacheNervous system disorders3/341/200/203/354/150/150/70/8
Abdominal painGastrointestinal disorders0/340/200/201/351/151/150/72/8
DizzinessNervous system disorders1/340/200/201/351/150/150/72/8
FlatulenceGastrointestinal disorders2/340/200/200/351/150/151/70/8

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cohort 1Cohort 2Total
Mean48.9 ± 7.958 ± 7.552.8 ± 8.9
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1Cohort 2Total
Female151328
Male527
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1Cohort 2Total
American Indian or Alaska Native181432
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American213
White000
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)Cohort 1Cohort 2Total
United States201535
Ethnicity
Ethnicity(Participants)Cohort 1Cohort 2Total
Hispanic or Latino10010
Not Hispanic or Latino101525
Body Mass Index (BMI)
Body Mass Index (BMI)(Kilogram per square meter (Kg/m^2))Cohort 1Cohort 2Total
Mean26.80 ± 3.1527.55 ± 2.3527.12 ± 2.82
08

Study locations

2 sites
  • Covance Clinical Research Unit
    Daytona Beach, Florida 32117, United States
  • Covance Clinical Research Unit
    Evansville, Indiana 47710, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 4, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02677844
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Feb 9, 2016
Start date
Feb 2016
Primary completion
Jul 2016
Completion
Jul 2016
Results posted
Aug 3, 2018
Last update
Jan 4, 2019

Study contacts

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)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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