A Study of LY2484595 in Healthy Subjects

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01450098
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 19.5

Study Details

Study Description

Brief Summary

The purpose of this study will be to evaluate the safety of a single dose of LY2484595 and to compare the amount of LY2484595 in the blood of healthy non-Asian subjects, Chinese subjects, and first-generation Japanese subjects after receiving a single oral dose of LY2484595 in a fasted state, after eating a low-fat meal, and after eating a high-fat meal.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2484595 Reference Formulation (RF); Drug: LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Single Dose LY2484595 Tablet Formulations to Determine the Impact of Dose Level, Food, and Ethnicity on the Pharmacokinetics in Healthy Subjects
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Fixed Sequence of Meal Conditions LY2484595 (evacetrapib): 200 milligrams (mg) of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with no food. There was a washout of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with low-fat breakfast. There was another washout period of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with high-fat breakfast.	Drug: LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG); Administered orally; Other Names: Evacetrapib
Experimental: Cohort B: Comparison of Randomized Treatments LY2484595 (evacetrapib): 100 mg of LY2484595 administered orally as an RF tablet given with a low-fat breakfast. There was a washout period of at least 14 days before crossing over and receiving 100 mg of LY2484595 administered orally as a SDSD-PG tablet given with a low-fat breakfast. There was another washout of at least 14 days before crossing over and receiving 300 mg of LY2484595 as a SDSD-PG tablet given with a low-fat breakfast.	Drug: LY2484595 Reference Formulation (RF); Administered orally; Other Names: Evacetrapib ; Drug: LY2484595 spray-dried solid dispersion-propyl gallate (SDSD-PG); Administered orally; Other Names: Evacetrapib

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595 [Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose]

   Area under the concentration-time curve from time zero to infinity is presented.

2. Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595 [Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose]

Secondary Outcome Measures

1. Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs [Baseline through completion of study (approximately 2 months)]

   Data presented are the number of participants who experienced one or more drug-related AEs or any serious AEs. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Are overtly healthy males or females, as determined by medical history and physical examination. For Cohort B, a first-generation Japanese subject is defined as one who is Japanese and was born in Japan and whose parents and all grandparents are Japanese and were born in Japan. A first-generation Chinese subject is defined as one who is Chinese and was born in China (mainland or Taiwan) and whose parents and all grandparents are Chinese and were born in China

• Female subjects are not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause. Women with an intact uterus are deemed postmenopausal if they are at least age 45, have had cessation of menses for at least 1 year, and have not taken hormones or oral contraceptives (including estrogen or hormone replacement therapy) during the past 12 months

• Have a body mass index (BMI) of 18.5 to 29.0 kilograms per meter squared (kg/m^2), inclusive

• Have clinical laboratory test results within normal reference range for the population or investigator site or results with acceptable deviations that are judged to be not clinically significant by the investigator

• Have an acceptable blood pressure (BP) and heart rate at both supine and standing positions as determined by the investigator (systolic BP less than or equal to 140 millimeters of mercury [mmHg], and diastolic BP less than or equal to 90 mmHg). A single, repeat BP measurement may be done at the discretion of the investigator

• Have venous access sufficient to allow blood sampling

• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

• Have given written informed consent approved by Eli Lilly and Company (hereafter, Lilly) and the ethical review board (ERB) governing the site

Exclusion Criteria:

• Are currently enrolled in or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Have known allergies to LY2484595 or related compounds

• Are persons who have previously completed or withdrawn from this study

• Have an abnormality in the 12-lead electrocardiogram (ECG) (including but not limited to a Bazett's corrected QT [QTcB] interval >450 milliseconds (msec) for men and >470 msec for women) that, in the opinion of the investigator, increases the risks associated with participating in the study

• Have a history within the last 2 years or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic 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

• Show evidence of significant active neuropsychiatric disease

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

• Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies

• Show evidence of hepatitis C and/or positive hepatitis C antibody

• Show evidence of hepatitis B and/or positive hepatitis B surface antigen

• Are women with a positive pregnancy test or women who are lactating

• Intend to use and actually use over-the-counter or prescription medication or dietary supplements within 14 days prior to dosing (acetaminophen is permissible on an as-needed basis at less than 3 grams per day for less than 7 days)

• Have donated blood of more than 500 milliliters (mL) within the last month

• Have an average alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption for 48 hours prior and during the inpatient confinement at the Clinical Research Unit (CRU) (1 unit = 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

• Use herbal supplements, grapefruit juice, grapefruits, Seville orange juice, Seville oranges, or starfruit within 7 days prior to study dosing

• Smoke more than 10 cigarettes per day currently and are unwilling to abide by the CRU guidelines

• Are unwilling to refrain from daily consumption of real licorice

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.	Glendale	California	United States	91206

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: NCT01450098
• Other Study ID Numbers: 13697; I1V-MC-EIAJ
• First Posted: Oct 12, 2011
• Last Update Posted: Oct 3, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Evacetrapib; Propyl Gallate

Study Results

Participant Flow

Arm/Group Title	Cohort A: Fixed Sequence of Meal Conditions	Cohort B: Comparison of Randomized Treatments
Arm/Group Description	LY2484595: 200 milligrams (mg) of LY2484595 administered orally, one time only, as a spray-dried solid dispersion-propyl gallate (SDSD-PG) tablet given with no food. There was a washout of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with low-fat breakfast. There was another washout period of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with high-fat breakfast.	LY2484595: 100 mg of LY2484595 administered orally as reference formulation (RF) tablet given with a low-fat breakfast. There was a washout period of at least 14 days before crossing over and receiving 100 mg of LY2484595 administered orally as a SDSD-PG tablet given with a low-fat breakfast. There was another washout of at least 14 days before crossing over and receiving 300 mg of LY2484595 as a SDSD-PG tablet given with a low-fat breakfast.
Period Title: Period 1
STARTED	8	31
Received at Least 1 Dose of Study Drug	8	31
COMPLETED	8	31
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	8	31
COMPLETED	8	31
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	8	31
Received at Least 1 Dose of Study Drug	8	31
COMPLETED	8	31
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	8	31
COMPLETED	8	31
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	8	31
Received at Least 1 Dose of Study Drug	8	30
COMPLETED	8	28
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Cohort A: Fixed Sequence of Meal Conditions	Cohort B: Comparison of Randomized Treatments	Total
Arm/Group Description	LY2484595: 200 milligrams (mg) of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with no food. There was a washout of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with low-fat breakfast. There was another washout period of at least 14 days before crossing over and receiving a 200 mg of LY2484595 administered orally, one time only, as a SDSD-PG tablet given with high-fat breakfast.	LY2484595: 100 mg of LY2484595 administered orally as an RF tablet given with a low-fat breakfast. There was a washout period of at least 14 days before crossing over and receiving 100 mg of LY2484595 administered orally as an SDSD-PG tablet given with a low-fat breakfast. There was another washout of at least 14 days before crossing over and receiving 300 mg of LY2484595 as a SDSD-PG tablet given with a low-fat breakfast.	Total of all reporting groups
Overall Participants	8	31	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.0 (6.2)	37.3 (11.4)	36.2 (10.73)
Sex: Female, Male (Count of Participants)
Female	0 0%	6 19.4%	6 15.4%
Male	8 100%	25 80.6%	33 84.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 25%	1 3.2%	3 7.7%
Not Hispanic or Latino	6 75%	30 96.8%	36 92.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 12.5%	0 0%	1 2.6%
Black or African American	1 12.5%	3 9.7%	4 10.3%
White	6 75%	6 19.4%	12 30.8%
Asian (Chinese)	0 0%	10 32.3%	10 25.6%
Asian (Japanese)	0 0%	11 35.5%	11 28.2%
Multiple	0 0%	1 3.2%	1 2.6%
Region of Enrollment (Count of Participants)
United States	8 100%	31 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2484595
Description	Area under the concentration-time curve from time zero to infinity is presented.
Time Frame	Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose

Outcome Measure Data

Analysis Population Description

All participants in Cohort A who received at least 1 dose of study drug with evaluable LY2484595 plasma concentration data

Arm/Group Title	LY2484595 200 mg SDSD-PG Fasted	LY2484595 200 mg SDSD-PG Low Fat	LY2484595 200 mg SDSD-PG High Fat
Arm/Group Description	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with no food	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with a low-fat breakfast	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with a high-fat breakfast
Measure Participants	7	8	7
Geometric Mean (Geometric Coefficient of Variation) [hours times nanograms per milliliter]	12200 (29)	17800 (31)	17800 (29)

2. Primary Outcome

Title	Pharmacokinetics: Peak Plasma Concentration (Cmax) of LY2484595
Time Frame	Predose and 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 168 hours postdose

Outcome Measure Data

Analysis Population Description

All participants in Cohort A who received at least 1 dose of study drug with evaluable LY2484595 maximum observed plasma concentration data

Arm/Group Title	LY2484595 200 mg SDSD-PG Fasted	LY2484595 200 mg SDSD-PG Low Fat	LY2484595 200 mg SDSD-PG High Fat
Arm/Group Description	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with no food	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with a low-fat breakfast	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with a high-fat breakfast
Measure Participants	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter]	828 (51)	1510 (30)	1280 (28)

3. Secondary Outcome

Title	Number of Participants With One or More Drug-related Adverse Events (AEs) or Any Serious AEs
Description	Data presented are the number of participants who experienced one or more drug-related AEs or any serious AEs. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame	Baseline through completion of study (approximately 2 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug

Arm/Group Title	LY2484595 100 mg RF	LY2484595 100 mg SDSD-PG	LY2484595 200 mg SDSD-PG	LY2484595 300 mg SDSD-PG
Arm/Group Description	Cohort B: 100 mg of LY2484595 administered orally one time as an RF tablet with a low-fat breakfast	Cohort B: 100 mg of LY2484595 administered orally one time as an SDSD-PG tablet with a low-fat breakfast.	Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with no food; then, after at least a 14 day washout period, 200 mg of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with a low-fat breakfast; then, after a washout period of at least 14 days, 200 mg of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with a high-fat breakfast	Cohort B: 300 mg of LY2484595 administered orally one time as an SDSD-PG tablet with a low-fat breakfast.
Measure Participants	30	30	8	31
Number [participants]	0 0%	0 0%	2 5.1%	1 NaN

Adverse Events

Arm/Group Title	LY2484595 100 mg RF		LY2484595 100 mg SDSD-PG		LY2484595 200 mg SDSD-PG		LY2484595 300 mg SDSD-PG
Arm/Group Description	Cohort B: 100 mg of LY2484595 administered orally one time as an RF tablet with a low-fat breakfast		Cohort B: 100 mg of LY2484595 administered orally one time as an SDSD-PG tablet with a low-fat breakfast.		Cohort A: 200 mg of LY2484595 administered orally, one time only as an SDSD-PG tablet given with no food; then, after at least a 14 day washout period, 200 mg of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with a low-fat breakfast; then, after a washout period of at least 14 days, 200 mg of LY2484595 administered orally, one time only, as an SDSD-PG tablet given with a high-fat breakfast		Cohort B: 300 mg of LY2484595 administered orally one time as an SDSD-PG tablet with a low-fat breakfast.
All Cause Mortality
	LY2484595 100 mg RF		LY2484595 100 mg SDSD-PG		LY2484595 200 mg SDSD-PG		LY2484595 300 mg SDSD-PG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2484595 100 mg RF		LY2484595 100 mg SDSD-PG		LY2484595 200 mg SDSD-PG		LY2484595 300 mg SDSD-PG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/8 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	LY2484595 100 mg RF		LY2484595 100 mg SDSD-PG		LY2484595 200 mg SDSD-PG		LY2484595 300 mg SDSD-PG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		3/8 (37.5%)		4/31 (12.9%)
Gastrointestinal disorders
Aphthous stomatitis	0/30 (0%)	0	0/30 (0%)	0	0/8 (0%)	0	1/31 (3.2%)	1
Flatulence	0/30 (0%)	0	0/30 (0%)	0	1/8 (12.5%)	1	0/31 (0%)	0
Infections and infestations
Gastroenteritis	0/30 (0%)	0	0/30 (0%)	0	0/8 (0%)	0	1/31 (3.2%)	1
Investigations
Transaminases increased	0/30 (0%)	0	0/30 (0%)	0	0/8 (0%)	0	1/31 (3.2%)	1
Nervous system disorders
Headache	0/30 (0%)	0	0/30 (0%)	0	1/8 (12.5%)	1	0/31 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/30 (0%)	0	0/30 (0%)	0	0/8 (0%)	0	1/31 (3.2%)	1
Epistaxis	0/30 (0%)	0	0/30 (0%)	0	1/8 (12.5%)	1	0/31 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/30 (0%)	0	0/30 (0%)	0	0/8 (0%)	0	1/31 (3.2%)	1

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.