Trial Outcomes & Findings for A Study of Abemaciclib in Participants With Varying Degrees of Liver Impairment (NCT NCT02387814)
NCT ID: NCT02387814
Last Updated: 2019-03-05
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
35 participants
Primary outcome timeframe
Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose
Results posted on
2019-03-05
Participant Flow
Participant milestones
| Measure |
Abemaciclib: Normal Hepatic Function
200 milligrams (mg) abemaciclib administered once, orally, to participants with normal hepatic function.
|
Abemaciclib: Mild Hepatic Impairment
200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.
|
Abemaciclib: Moderate Hepatic Impairment
200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.
|
Abemaciclib: Severe Hepatic Impairment
200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
9
|
10
|
6
|
|
Overall Study
Received Abemaciclib
|
10
|
9
|
10
|
6
|
|
Overall Study
COMPLETED
|
10
|
9
|
10
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Abemaciclib in Participants With Varying Degrees of Liver Impairment
Baseline characteristics by cohort
| Measure |
Abemaciclib: Normal Hepatic Function
n=10 Participants
200 mg abemaciclib administered once, orally, to participants with normal hepatic function.
|
Abemaciclib: Mild Hepatic Impairment
n=9 Participants
200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.
|
Abemaciclib: Moderate Hepatic Impairment
n=10 Participants
200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.
|
Abemaciclib: Severe Hepatic Impairment
n=6 Participants
200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
55.0 years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
56.6 years
STANDARD_DEVIATION 4.4 • n=7 Participants
|
58.8 years
STANDARD_DEVIATION 5.5 • n=5 Participants
|
53.2 years
STANDARD_DEVIATION 6.2 • n=4 Participants
|
56.2 years
STANDARD_DEVIATION 5.3 • n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
27 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
35 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours PostdosePopulation: All participants who received abemaciclib and had evaluable plasma values.
Outcome measures
| Measure |
Abemaciclib: Normal Hepatic Function
n=10 Participants
200 mg abemaciclib administered once, orally, to participants with normal hepatic function.
|
Abemaciclib: Mild Hepatic Impairment
n=9 Participants
200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.
|
Abemaciclib: Moderate Hepatic Impairment
n=10 Participants
200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.
|
Abemaciclib: Severe Hepatic Impairment
n=6 Participants
200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites
Abemaciclib
|
133 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 63
|
109 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 65
|
83.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 47
|
156 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 44
|
|
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites
LSN2839567
|
31.2 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 57
|
26.0 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 31
|
13.6 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 71
|
17.4 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 45
|
|
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites
LSN3106729
|
10.4 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 47
|
6.24 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 27
|
4.96 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 90
|
2.70 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 41
|
|
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites
LSN3106726
|
55.3 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 40
|
37.7 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 35
|
19.2 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 71
|
14.0 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 27
|
PRIMARY outcome
Timeframe: Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours PostdosePopulation: All participants who received abemaciclib and had evaluable plasma values.
Outcome measures
| Measure |
Abemaciclib: Normal Hepatic Function
n=10 Participants
200 mg abemaciclib administered once, orally, to participants with normal hepatic function.
|
Abemaciclib: Mild Hepatic Impairment
n=9 Participants
200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.
|
Abemaciclib: Moderate Hepatic Impairment
n=10 Participants
200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.
|
Abemaciclib: Severe Hepatic Impairment
n=6 Participants
200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
|
|---|---|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites
Abemaciclib
|
4460 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 61
|
4280 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 58
|
4940 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 51
|
9310 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 49
|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites
LSN2839567
|
1420 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 40
|
1090 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 34
|
921 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 46
|
846 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 33
|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites
LSN3106729
|
480 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 55
|
257 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 42
|
211 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 251
|
35.3 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation NA
Due to lack of samples with quantifiable LSN3106729 concentrations, AUC(0-inf) could only be calculated for 1 participant. (Individual value: 35.3 ng\*h/mL).
|
|
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites
LSN3106726
|
3120 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 40
|
2200 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 39
|
1570 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 57
|
1170 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 30
|
Adverse Events
Abemaciclib: Normal Hepatic Function
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Abemaciclib: Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Abemaciclib: Moderate Hepatic Impairment
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Abemaciclib: Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Abemaciclib: Normal Hepatic Function
n=10 participants at risk
200 mg abemaciclib administered once, orally, to participants with normal hepatic function.
|
Abemaciclib: Mild Hepatic Impairment
n=9 participants at risk
200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.
|
Abemaciclib: Moderate Hepatic Impairment
n=10 participants at risk
200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.
|
Abemaciclib: Severe Hepatic Impairment
n=6 participants at risk
200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
|
|---|---|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
Other adverse events
| Measure |
Abemaciclib: Normal Hepatic Function
n=10 participants at risk
200 mg abemaciclib administered once, orally, to participants with normal hepatic function.
|
Abemaciclib: Mild Hepatic Impairment
n=9 participants at risk
200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.
|
Abemaciclib: Moderate Hepatic Impairment
n=10 participants at risk
200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.
|
Abemaciclib: Severe Hepatic Impairment
n=6 participants at risk
200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
10.0%
1/10 • Number of events 1
|
0.00%
0/9
|
0.00%
0/10
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/10
|
11.1%
1/9 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/10
|
11.1%
1/9 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10
|
11.1%
1/9 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/10
|
11.1%
1/9 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/10
|
0.00%
0/9
|
0.00%
0/10
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Catheter site erythema
|
0.00%
0/10
|
22.2%
2/9 • Number of events 2
|
0.00%
0/10
|
0.00%
0/6
|
|
General disorders
Catheter site pain
|
0.00%
0/10
|
11.1%
1/9 • Number of events 1
|
0.00%
0/10
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Fatigue
|
0.00%
0/10
|
0.00%
0/9
|
20.0%
2/10 • Number of events 2
|
0.00%
0/6
|
|
General disorders
Malaise
|
0.00%
0/10
|
11.1%
1/9 • Number of events 1
|
0.00%
0/10
|
0.00%
0/6
|
|
Infections and infestations
Bronchitis
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/10
|
0.00%
0/9
|
0.00%
0/10
|
16.7%
1/6 • Number of events 1
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
|
Investigations
White blood cell count decreased
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/10
|
22.2%
2/9 • Number of events 2
|
0.00%
0/10
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
30.0%
3/10 • Number of events 3
|
22.2%
2/9 • Number of events 2
|
10.0%
1/10 • Number of events 2
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/10
|
22.2%
2/9 • Number of events 2
|
0.00%
0/10
|
0.00%
0/6
|
|
Vascular disorders
Hypotension
|
0.00%
0/10
|
0.00%
0/9
|
10.0%
1/10 • Number of events 1
|
0.00%
0/6
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60