A Study of Evacetrapib (LY2484595) in Participants With Hepatic (Liver) Impairment

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01836185
• Collaborator: (none)
• Enrollment: 32
• Locations: 2
• Arms: 4
• Duration (Months): 6
• Patients Per Site: 16
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

The purpose of this study is to measure how much of the drug gets into the bloodstream and how long it takes the body to remove it when given to participants with hepatic (liver) impairment compared to participants with normal hepatic function. Information about any side effects that may occur will also be collected. This study will last approximately 28 days, not including screening.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Pharmacokinetics of Evacetrapib (LY2484595) in Subjects With Hepatic Impairment
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Evacetrapib (Healthy) Group 1: 130 milligrams (mg) evacetrapib administered once, orally, to participants with normal hepatic function	Drug: Evacetrapib; Other Names: LY2484595
Experimental: Evacetrapib (Hepatic, Mild) Group 2: 130 mg evacetrapib administered once, orally, to participants with mild hepatic impairment	Drug: Evacetrapib; Other Names: LY2484595
Experimental: Evacetrapib (Hepatic, Moderate) Group 3: 130 mg evacetrapib administered once, orally, to participants with moderate hepatic impairment	Drug: Evacetrapib; Other Names: LY2484595
Experimental: Evacetrapib (Hepatic, Severe) Group 4: 130 mg evacetrapib administered once, orally, to participants with severe hepatic impairment	Drug: Evacetrapib; Other Names: LY2484595

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib [Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose]

   tlast is defined as the last time point with a measurable concentration of Evacetrapib.

2. PK: Maximum Observed Concentration (Cmax) of Evacetrapib [Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose]

3. PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib [Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants have given written informed consent approved by the ethical review board (ERB) governing the site

• Female participants should be of non-childbearing potential

• Have a body mass index (BMI) of 18 to 40 kilograms per square meter (kg/m^2)

• Healthy participants have normal hepatic function as determined by medical history, physical examination, and other screening procedures

• Individuals with hepatic impairment classified as Child-Pugh score A, B, or C (mild, moderate, or severe impairment)

Exclusion Criteria:

• Has had esophagus variceal bleeding within 3 months of check-in

• Have the need to take medications that may interfere with how the liver removes the drug

• Have evidence of cancer in the liver

• Consumes excessively large amounts of drinks with caffeine or alcohol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Miami	Florida	United States	33169
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Orlando	Florida	United States	32806

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: NCT01836185
• Other Study ID Numbers: 14621; I1V-MC-EIAS
• First Posted: Apr 19, 2013
• Last Update Posted: Oct 12, 2018
• Last Verified: Oct 1, 2018

• Additional relevant MeSH terms: Hepatic Insufficiency; Liver Failure; Evacetrapib

Study Results

Participant Flow

Arm/Group Title	Evacetrapib (Healthy)	Evacetrapib (Hepatic, Mild)	Evacetrapib (Hepatic, Moderate)	Evacetrapib (Hepatic, Severe)
Arm/Group Description	Group 1: 130 milligrams (mg) evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Period Title: Overall Study
STARTED	10	8	8	6
Received Single Dose of Study Treatment	10	8	8	6
COMPLETED	10	8	8	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Evacetrapib (Healthy)	Evacetrapib (Hepatic, Mild)	Evacetrapib (Hepatic, Moderate)	Evacetrapib (Hepatic, Severe)	Total
Arm/Group Description	Group 1: 130 milligrams (mg) evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment	Total of all reporting groups
Overall Participants	10	8	8	6	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.4 (8.6)	54.1 (2.9)	58.6 (9.6)	57.8 (4.7)	56.0 (7.2)
Sex: Female, Male (Count of Participants)
Female	4 40%	4 50%	2 25%	1 16.7%	11 34.4%
Male	6 60%	4 50%	6 75%	5 83.3%	21 65.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 80%	2 25%	4 50%	3 50%	17 53.1%
Not Hispanic or Latino	2 20%	6 75%	4 50%	3 50%	15 46.9%
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%	0 0%	0 0%
Asian	0 0%	1 12.5%	0 0%	0 0%	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 10%	1 12.5%	0 0%	0 0%	2 6.3%
White	9 90%	6 75%	8 100%	6 100%	29 90.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	8 100%	8 100%	6 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib
Description	tlast is defined as the last time point with a measurable concentration of Evacetrapib.
Time Frame	Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug and had evaluable PK (AUC0-tlast) data.

Arm/Group Title	Evacetrapib (Healthy)	Evacetrapib (Hepatic, Mild)	Evacetrapib (Hepatic, Moderate)	Evacetrapib (Hepatic, Severe)
Arm/Group Description	Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Measure Participants	10	8	8	6
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per milliliter (ng*h/mL)]	10700 (50)	10500 (84)	13200 (49)	15800 (62)

2. Primary Outcome

Title	PK: Maximum Observed Concentration (Cmax) of Evacetrapib
Time Frame	Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study drug and had evaluable PK (Cmax) data.

Arm/Group Title	Evacetrapib (Healthy)	Evacetrapib (Hepatic, Mild)	Evacetrapib (Hepatic, Moderate)	Evacetrapib (Hepatic, Severe)
Arm/Group Description	Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Measure Participants	10	8	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	605 (98)	609 (144)	591 (58)	478 (51)

3. Primary Outcome

Title	PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib
Time Frame	Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Evacetrapib (Healthy)	Evacetrapib (Hepatic, Mild)	Evacetrapib (Hepatic, Moderate)	Evacetrapib (Hepatic, Severe)
Arm/Group Description	Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Measure Participants	10	8	8	6
Mean (Full Range) [h]	3	3	3	3

Adverse Events

Time Frame	Randomization to study completion (Up To 41 Days)
Arm/Group Title	Evacetrapib (Healthy)		Evacetrapib (Hepatic, Mild)		Evacetrapib (Hepatic, Moderate)		Evacetrapib (Hepatic, Severe)
Arm/Group Description	Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function		Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment		Group 3: 130 mg evacetrapib administered once, orally, as a tablet to participants with moderate hepatic impairment		Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
All Cause Mortality
	Evacetrapib (Healthy)		Evacetrapib (Hepatic, Mild)		Evacetrapib (Hepatic, Moderate)		Evacetrapib (Hepatic, Severe)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Evacetrapib (Healthy)		Evacetrapib (Hepatic, Mild)		Evacetrapib (Hepatic, Moderate)		Evacetrapib (Hepatic, Severe)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)		0/8 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Evacetrapib (Healthy)		Evacetrapib (Hepatic, Mild)		Evacetrapib (Hepatic, Moderate)		Evacetrapib (Hepatic, Severe)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		4/8 (50%)		3/8 (37.5%)		3/6 (50%)
Gastrointestinal disorders
Abdominal pain	0/10 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/6 (16.7%)	1
Abdominal pain upper	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0
Constipation	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/6 (16.7%)	1
Diarrhoea	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	2/6 (33.3%)	3
Flatulence	1/10 (10%)	1	1/8 (12.5%)	1	0/8 (0%)	0	0/6 (0%)	0
Vomiting	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/6 (16.7%)	1
Infections and infestations
Viral infection	0/10 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/6 (0%)	0
Injury, poisoning and procedural complications
Laceration	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0
Nervous system disorders
Dizziness	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0
Headache	1/10 (10%)	1	0/8 (0%)	0	0/8 (0%)	0	1/6 (16.7%)	1
Somnolence	0/10 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	1/10 (10%)	1	0/8 (0%)	0	0/8 (0%)	0	0/6 (0%)	0
Ecchymosis	0/10 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/6 (16.7%)	1
Piloerection	0/10 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/6 (0%)	0
Rash papular	0/10 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	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.