A Study of Evacetrapib (LY2484595) in Participants With Severe Renal Impairment and in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01825889
• Collaborator: (none)
• Enrollment: 20
• Locations: 3
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 6.7
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The purpose of this study is to measure how much of the study drug, evacetrapib, enters the blood stream and how long it takes the body to dispose of the study drug when given to participants with severe renal (kidney) impairment compared to participants with normal renal (kidney) function. This study will last approximately 8 weeks.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Drug: Evacetrapib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Pharmacokinetics of Evacetrapib (LY2484595) Following Administration to Subjects With Impaired Renal Function
• 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 (Participants With Renal Impairment) Single oral dose of 130 milligrams (mg) evacetrapib on Day 1 to participants with severe renal impairment.	Drug: Evacetrapib; Other Names: LY2484595
Experimental: Evacetrapib (Healthy Participants) Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.	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, Where Tlast is the Last Time Point With a Measurable Concentration (AUC[0-Tlast]) of Evacetrapib [Predose and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours postdose]

2. Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Evacetrapib [Predose and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours postdose]

Secondary Outcome Measures

1. Pharmacokinetics (PK): Observed Maximum Concentration (Cmax) of Evacetrapib [Predose and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 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 are not of child-bearing potential

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

• Participants with normal renal function - healthy as determined by medical history, physical examination, and other screening procedures, with normal renal function (assessed by estimated creatinine clearance [CLcr] greater than or equal to 90 milliliters per minute [mL/min] at screening)

• Participants with severe renal impairment - estimated CLcr less than 30 mL/min at screening and are not undergoing hemodialysis

Exclusion Criteria:

• 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; of constituting a risk when taking the study medication; or of interfering with the interpretation of data

• Participants who are unwilling to comply with the dietary requirements/restrictions during the study

• Hemoglobin less than 9 grams/deciliter (g/dL) or significant active hematological disease from causes other than underlying renal disease

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	33014
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
3	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.	Saint Paul	Minnesota	United States	55114

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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: NCT01825889
• Other Study ID Numbers: 14620; I1V-MC-EIAR
• First Posted: Apr 8, 2013
• Last Update Posted: Oct 9, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Cardiovascular Diseases; Evacetrapib

Study Results

Participant Flow

Arm/Group Title	Evacetrapib (Participants With Renal Impairment)	Evacetrapib (Healthy Participants)
Arm/Group Description	Single oral dose of 130 milligrams (mg) evacetrapib on Day 1 to participants with severe renal impairment.	Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.
Period Title: Overall Study
STARTED	10	10
Received One Dose of Study Drug	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Evacetrapib (Participants With Renal Impairment)	Evacetrapib (Healthy Participants)	Total
Arm/Group Description	Single oral dose of 130 mg evacetrapib on Day 1 to participants with severe renal impairment.	Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (9.6)	61.5 (8.0)	63.4 (8.8)
Sex: Female, Male (Count of Participants)
Female	4 40%	4 40%	8 40%
Male	6 60%	6 60%	12 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 60%	5 50%	11 55%
Not Hispanic or Latino	4 40%	5 50%	9 45%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 40%	0 0%	4 20%
White	6 60%	9 90%	15 75%
More than one race	0 0%	1 10%	1 5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under The Concentration Versus Time Curve From Time Zero To Time Tlast, Where Tlast is the Last Time Point With a Measurable Concentration (AUC[0-Tlast]) of Evacetrapib
Time Frame	Predose and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received evacetrapib and had evaluable AUC(0-Tlast) data.

Arm/Group Title	Evacetrapib (Participants With Renal Impairment)	Evacetrapib (Healthy Participants)
Arm/Group Description	Single oral dose of 130 mg evacetrapib on Day 1 to participants with severe renal impairment.	Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.
Measure Participants	10	10
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours/milliliter (ng*h/mL)]	15200 (49)	16000 (37)

2. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Evacetrapib
Time Frame	Predose and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who received evacetrapib and had evaluable AUC(0-∞) data.

Arm/Group Title	Evacetrapib (Participants With Renal Impairment)	Evacetrapib (Healthy Participants)
Arm/Group Description	Single oral dose of 130 mg evacetrapib on Day 1 to participants with severe renal impairment.	Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.
Measure Participants	10	10
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	15500 (50)	16300 (39)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received evacetrapib and had evaluable Cmax data.

Arm/Group Title	Evacetrapib (Participants With Renal Impairment)	Evacetrapib (Healthy Participants)
Arm/Group Description	Single oral dose of 130 mg evacetrapib on Day 1 to participants with severe renal impairment.	Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.
Measure Participants	10	10
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	969 (43)	1140 (44)

Adverse Events

Arm/Group Title	Evacetrapib (Participants With Renal Impairment)		Evacetrapib (Healthy Participants)
Arm/Group Description	Single oral dose of 130 mg evacetrapib on Day 1 to participants with severe renal impairment.		Single oral dose of 130 mg evacetrapib on Day 1 to participants with normal renal function.
All Cause Mortality
	Evacetrapib (Participants With Renal Impairment)		Evacetrapib (Healthy Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Evacetrapib (Participants With Renal Impairment)		Evacetrapib (Healthy Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Evacetrapib (Participants With Renal Impairment)		Evacetrapib (Healthy Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/10 (30%)		2/10 (20%)
Gastrointestinal disorders
Abdominal distension	1/10 (10%)	1	0/10 (0%)	0
Diarrhoea	0/10 (0%)	0	1/10 (10%)	1
General disorders
Vessel puncture site haematoma	0/10 (0%)	0	1/10 (10%)	1
Vessel puncture site swelling	0/10 (0%)	0	1/10 (10%)	1
Injury, poisoning and procedural complications
Muscle strain	0/10 (0%)	0	1/10 (10%)	1
Metabolism and nutrition disorders
Gout	1/10 (10%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Dizziness	1/10 (10%)	1	0/10 (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.