A Study of Evacetrapib in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01736254
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 2
• Patients Per Site Per Month: 11.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether concentrations of the study drug (evacetrapib) in the blood stream is the same or is different when the person is also taking gemfibrozil (a drug used to lower lipid levels). Each participant will receive gemfibrozil alone, evacetrapib alone, and both drugs in combination. There is no washout period between doses. The safety of both of the study drugs given together will be evaluated. Information about any side effects that may have occurred will also be collected. This study will last approximately 36 days.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Evacetrapib; Drug: Gemfibrozil	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Gemfibrozil on the Pharmacokinetics of Evacetrapib (LY2484595) in Healthy Subjects
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemfibrozil Single oral dose of 600 milligrams (mg) gemfibrozil on Day 1	Drug: Gemfibrozil
Experimental: Evacetrapib Oral doses of 130 mg evacetrapib once a day (QD) for 10 days (Day 2 through Day 12)	Drug: Evacetrapib; Other Names: LY2484595
Experimental: Evacetrapib + Gemfibrozil Oral doses of 600 mg gemfibrozil twice a day (BID) and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.	Drug: Evacetrapib; Other Names: LY2484595 ; Drug: Gemfibrozil

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib [Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22]

   Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.

2. Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib [Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22]

   Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.

3. Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib [Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22]

   Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil [Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13]

   Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.

2. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil [Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13]

   Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.

3. Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil [Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13]

   Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy participants as determined by medical history and physical examination

• Have a body mass index of 18 to 32 kilograms per square meter (kg/m^2)

Exclusion Criteria:

• Have known allergies to evacetrapib and gemfibrozil, related compounds or any components of the formulation

• Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study

• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening

• Currently smoke cigarettes or use tobacco or nicotine substitutes

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.	Daytona Beach	Florida	United States	32117

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: NCT01736254
• Other Study ID Numbers: 14701; I1V-MC-EIBD
• First Posted: Nov 29, 2012
• Last Update Posted: Oct 3, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Gemfibrozil; Evacetrapib

Study Results

Participant Flow

Arm/Group Title	All Participants
Arm/Group Description	All participants were assigned to the following treatment regimen: Period 1: Single oral dose of 600 milligrams (mg) gemfibrozil in the morning of Day 1. Period 2: Oral doses of 130 mg evacetrapib once a day (QD) for 11 days (Days 2 to 12). Period 3: Oral doses of 600 mg gemfibrozil twice a day (BID) and 130 mg evacetrapib QD for 10 days (Days 13 to 22), with a single dose of 600 mg gemfibrozil on Day 23.
Period Title: Period 1 (Day 1)
STARTED	24
Received at Least One Dose of Study Drug	24
COMPLETED	24
NOT COMPLETED	0
Period Title: Period 1 (Day 1)
STARTED	24
COMPLETED	21
NOT COMPLETED	3
Period Title: Period 1 (Day 1)
STARTED	21
COMPLETED	20
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants were assigned to the following treatment regimen: Period 1: Single oral dose of 600 mg gemfibrozil in the morning of Day 1. Period 2: Oral doses of 130 mg evacetrapib QD for 11 days (Days 2 to 12). Period 3: Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Days 13 to 22), with a single dose of 600 mg gemfibrozil on Day 23.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (10.4)
Sex: Female, Male (Count of Participants)
Female	2 8.3%
Male	22 91.7%
Race/Ethnicity, Customized (Count of Participants)
White	14 58.3%
Black	7 29.2%
Multiple	3 12.5%
Region of Enrollment (Count of Participants)
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib
Description	Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Cmax data.

Arm/Group Title	Evacetrapib	Evacetrapib + Gemfibrozil
Arm/Group Description	Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).	Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
Measure Participants	22	20
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	1270 (26)	1290 (26)

2. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib
Description	Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable AUCτ data.

Arm/Group Title	Evacetrapib	Evacetrapib + Gemfibrozil
Arm/Group Description	Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).	Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
Measure Participants	22	19
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours/milliliter (ng*h/mL)]	11300 (20)	11400 (21)

3. Primary Outcome

Title	Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib
Description	Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Tmax data.

Arm/Group Title	Evacetrapib	Evacetrapib + Gemfibrozil
Arm/Group Description	Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).	Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
Measure Participants	22	20
Median (Full Range) [hours]	4.00	3.00

4. Secondary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil
Description	Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable AUCτ data.

Arm/Group Title	Gemfibrozil	Evacetrapib + Gemfibrozil
Arm/Group Description	Single oral dose of 600 mg gemfibrozil on Day 1.	Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
Measure Participants	24	21
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	55700 (23)	53800 (22)

5. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil
Description	Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Cmax data.

Arm/Group Title	Gemfibrozil	Evacetrapib + Gemfibrozil
Arm/Group Description	Single oral dose of 600 mg gemfibrozil on Day 1.	Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
Measure Participants	24	21
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	17400 (32)	16800 (34)

6. Secondary Outcome

Title	Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil
Description	Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Time Frame	Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Tmax data.

Arm/Group Title	Gemfibrozil	Evacetrapib + Gemfibrozil
Arm/Group Description	Single oral dose of 600 mg gemfibrozil on Day 1.	Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
Measure Participants	24	21
Median (Full Range) [hours]	1.00	1.08

Adverse Events

Arm/Group Title	Gemfibrozil		Evacetrapib		Evacetrapib + Gemfibrozil
Arm/Group Description	Single oral dose of 600 mg gemfibrozil on Day 1.		Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).		Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
All Cause Mortality
	Gemfibrozil		Evacetrapib		Evacetrapib + Gemfibrozil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Gemfibrozil		Evacetrapib		Evacetrapib + Gemfibrozil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Gemfibrozil		Evacetrapib		Evacetrapib + Gemfibrozil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/24 (4.2%)		8/24 (33.3%)		7/21 (33.3%)
Eye disorders
Lacrimation increased	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Ocular hyperaemia	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Gastrointestinal disorders
Bowel movement irregularity	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Diarrhoea	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Flatulence	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Glossitis	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Tongue disorder	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Toothache	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Infections and infestations
Hordeolum	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Investigations
Liver function test abnormal	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	0/24 (0%)	0	0/24 (0%)	0	2/21 (9.5%)	2
Nervous system disorders
Headache	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Psychiatric disorders
Insomnia	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/24 (4.2%)	1	1/24 (4.2%)	1	0/21 (0%)	0
Dry throat	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Nasal congestion	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Oropharyngeal pain	0/24 (0%)	0	2/24 (8.3%)	2	0/21 (0%)	0
Pulmonary congestion	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Sneezing	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Pruritus	0/24 (0%)	0	1/24 (4.2%)	1	1/21 (4.8%)	1
Rash	0/24 (0%)	0	0/24 (0%)	0	1/21 (4.8%)	1
Vascular disorders
Flushing	0/24 (0%)	0	1/24 (4.2%)	1	0/21 (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.