A Study of Abemaciclib in Participants With Varying Degrees of Liver Impairment

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02387814
• Collaborator: (none)
• Enrollment: 35
• Locations: 5
• Arms: 4
• Duration (Months): 5
• Patients Per Site: 7
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The study involves a single dose of a study drug called abemaciclib taken by mouth. The purpose of this study will be to measure how much study drug gets into the blood stream and how long the body takes to get rid of it when given to participants with mild, moderate, or severe liver impairment compared to healthy participants. In addition, the tolerability of the study drug will be evaluated.

This study will last approximately 3 weeks for each participant, including check-in and follow-up.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Insufficiency	Drug: Abemaciclib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Single-Dose Pharmacokinetic Study of Abemaciclib (LY2835219) in Subjects With Varying Degrees of Hepatic Impairment
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abemaciclib: Normal Hepatic Function Single dose of Abemaciclib administered orally on Day 1 to participants with normal hepatic function.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219
Experimental: Abemaciclib: Mild Hepatic Impairment Single dose of Abemaciclib administered orally on Day 1 to participants with mild hepatic impairment.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219
Experimental: Abemaciclib: Moderate Hepatic Impairment Single dose of Abemaciclib administered orally on Day 1 to participants with moderate hepatic impairment.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219
Experimental: Abemaciclib: Severe Hepatic Impairment Single dose of Abemaciclib administered orally on Day 1 to participants with severe hepatic impairment.	Drug: Abemaciclib; Administered Orally; Other Names: LY2835219

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites [Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose]

2. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites [Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Female participants must be of non-child-bearing potential

• Have a body mass index of 18 to 40 kilograms per square meter (kg/m²)

Exclusion Criteria:

• No history of cardiovascular, renal, respiratory, gastrointestinal, endocrine or hematological disorders

• Have known allergies to abemaciclib, related compounds, or any components of the formulation

• No human immunodeficiency virus (HIV) infection or antibodies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	DaVita Clinical Research	Lakewood	Colorado	United States	80228
2	Clinical Pharmacology of Miami (CPMI)	Miami	Florida	United States	33014
3	Orlando Clinical Research Center (OCRC)	Orlando	Florida	United States	32809
4	Indiana University - Digestive and Liver Diseases	Indianapolis	Indiana	United States	46202
5	DaVita Clinical Research	Minneapolis	Minnesota	United States	55404

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02387814
• Other Study ID Numbers: 15538; I3Y-MC-JPBV
• First Posted: Mar 13, 2015
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Additional relevant MeSH terms: Hepatic Insufficiency; Liver Failure

Study Results

Participant Flow

Arm/Group Title	Abemaciclib: Normal Hepatic Function	Abemaciclib: Mild Hepatic Impairment	Abemaciclib: Moderate Hepatic Impairment	Abemaciclib: Severe Hepatic Impairment
Arm/Group Description	200 milligrams (mg) abemaciclib administered once, orally, to participants with normal hepatic function.	200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
Period Title: Overall Study
STARTED	10	9	10	6
Received Abemaciclib	10	9	10	6
COMPLETED	10	9	10	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Abemaciclib: Normal Hepatic Function	Abemaciclib: Mild Hepatic Impairment	Abemaciclib: Moderate Hepatic Impairment	Abemaciclib: Severe Hepatic Impairment	Total
Arm/Group Description	200 mg abemaciclib administered once, orally, to participants with normal hepatic function.	200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.	Total of all reporting groups
Overall Participants	10	9	10	6	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.0 (4.8)	56.6 (4.4)	58.8 (5.5)	53.2 (6.2)	56.2 (5.3)
Sex: Female, Male (Count of Participants)
Female	5 50%	3 33.3%	3 30%	2 33.3%	13 37.1%
Male	5 50%	6 66.7%	7 70%	4 66.7%	22 62.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 20%	2 22.2%	0 0%	4 66.7%	8 22.9%
Not Hispanic or Latino	8 80%	7 77.8%	10 100%	2 33.3%	27 77.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 16.7%	1 2.9%
Asian	0 0%	1 11.1%	0 0%	0 0%	1 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 30%	1 11.1%	3 30%	0 0%	7 20%
White	7 70%	7 77.8%	7 70%	4 66.7%	25 71.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	1 16.7%	1 2.9%
Region of Enrollment (Count of Participants)
United States	10 100%	9 100%	10 100%	6 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites
Time Frame	Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose

Outcome Measure Data

Analysis Population Description

All participants who received abemaciclib and had evaluable plasma values.

Arm/Group Title	Abemaciclib: Normal Hepatic Function	Abemaciclib: Mild Hepatic Impairment	Abemaciclib: Moderate Hepatic Impairment	Abemaciclib: Severe Hepatic Impairment
Arm/Group Description	200 mg abemaciclib administered once, orally, to participants with normal hepatic function.	200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
Measure Participants	10	9	10	6
Abemaciclib	133 (63)	109 (65)	83.9 (47)	156 (44)
LSN2839567	31.2 (57)	26.0 (31)	13.6 (71)	17.4 (45)
LSN3106729	10.4 (47)	6.24 (27)	4.96 (90)	2.70 (41)
LSN3106726	55.3 (40)	37.7 (35)	19.2 (71)	14.0 (27)

2. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites
Time Frame	Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose

Outcome Measure Data

Analysis Population Description

All participants who received abemaciclib and had evaluable plasma values.

Arm/Group Title	Abemaciclib: Normal Hepatic Function	Abemaciclib: Mild Hepatic Impairment	Abemaciclib: Moderate Hepatic Impairment	Abemaciclib: Severe Hepatic Impairment
Arm/Group Description	200 mg abemaciclib administered once, orally, to participants with normal hepatic function.	200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.	200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
Measure Participants	10	9	10	6
Abemaciclib	4460 (61)	4280 (58)	4940 (51)	9310 (49)
LSN2839567	1420 (40)	1090 (34)	921 (46)	846 (33)
LSN3106729	480 (55)	257 (42)	211 (251)	35.3 (NA)
LSN3106726	3120 (40)	2200 (39)	1570 (57)	1170 (30)

Adverse Events

Arm/Group Title	Abemaciclib: Normal Hepatic Function		Abemaciclib: Mild Hepatic Impairment		Abemaciclib: Moderate Hepatic Impairment		Abemaciclib: Severe Hepatic Impairment
Arm/Group Description	200 mg abemaciclib administered once, orally, to participants with normal hepatic function.		200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment.		200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment.		200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment.
All Cause Mortality
	Abemaciclib: Normal Hepatic Function		Abemaciclib: Mild Hepatic Impairment		Abemaciclib: Moderate Hepatic Impairment		Abemaciclib: Severe Hepatic Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Abemaciclib: Normal Hepatic Function		Abemaciclib: Mild Hepatic Impairment		Abemaciclib: Moderate Hepatic Impairment		Abemaciclib: Severe Hepatic Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)		1/10 (10%)		0/6 (0%)
Infections and infestations
Pneumonia	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0
Other (Not Including Serious) Adverse Events
	Abemaciclib: Normal Hepatic Function		Abemaciclib: Mild Hepatic Impairment		Abemaciclib: Moderate Hepatic Impairment		Abemaciclib: Severe Hepatic Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		6/9 (66.7%)		7/10 (70%)		3/6 (50%)
Gastrointestinal disorders
Abdominal discomfort	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/6 (0%)	0
Abdominal distension	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0
Abdominal pain	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0
Constipation	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0
Diarrhoea	0/10 (0%)	0	1/9 (11.1%)	1	1/10 (10%)	1	0/6 (0%)	0
Gastrooesophageal reflux disease	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0
Nausea	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	1/6 (16.7%)	1
Salivary hypersecretion	0/10 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1
General disorders
Catheter site erythema	0/10 (0%)	0	2/9 (22.2%)	2	0/10 (0%)	0	0/6 (0%)	0
Catheter site pain	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	1/6 (16.7%)	1
Fatigue	0/10 (0%)	0	0/9 (0%)	0	2/10 (20%)	2	0/6 (0%)	0
Malaise	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/6 (0%)	0
Infections and infestations
Bronchitis	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Laceration	0/10 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/6 (16.7%)	1
Skin abrasion	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0
Investigations
White blood cell count decreased	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0
Nervous system disorders
Dysgeusia	0/10 (0%)	0	2/9 (22.2%)	2	0/10 (0%)	0	0/6 (0%)	0
Headache	3/10 (30%)	3	2/9 (22.2%)	2	1/10 (10%)	2	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/10 (0%)	0	2/9 (22.2%)	2	0/10 (0%)	0	0/6 (0%)	0
Vascular disorders
Hypotension	0/10 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.