A Study of Evacetrapib in Japanese and Non-Japanese Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01958489
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 3
• Patients Per Site Per Month: 7.9

Study Details

Study Description

Brief Summary

The main purpose of this study is to look at the effect of evacetrapib on pravastatin levels in the blood when both drugs are taken at the same time. The study will also assess how well the body handles evacetrapib and pravastatin when given at the same time.

This study has two periods in fixed order. Each participant will enroll in both periods. This study will last approximately 25 days, not including screening.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Evacetrapib; Drug: Pravastatin	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 Evacetrapib on the Pharmacokinetics of Pravastatin in Healthy Japanese and Non-Japanese Subjects
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pravastatin Single 40 milligram (mg) oral dose of pravastatin administered on Day 1.	Drug: Pravastatin; Administered orally
Experimental: Evacetrapib + Pravastatin Oral doses of 130 mg evacetrapib administered once daily on Days 2 through 11, with a single oral dose of 40 mg pravastatin coadministered on Day 11.	Drug: Evacetrapib; Administered orally; Other Names: LY2484595 ; Drug: Pravastatin; Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Pravastatin [Day 1 and Day 11: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose]

2. PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pravastatin [Day 1 and Day 11: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose]

3. PK: Time of Maximum Observed Concentration (Tmax) of Pravastatin [Day 1 and Day 11: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Overtly healthy participants, as determined by medical history and physical examination

• Have a body mass index of 18 to 32 kilograms per square meter (kg/m²)

• Japanese participants must be first generation Japanese

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.	Leeds	West Yorkshire	United Kingdom	LS2 9LH

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: NCT01958489
• Other Study ID Numbers: 14625; I1V-MC-EIAW
• First Posted: Oct 9, 2013
• Last Update Posted: Oct 9, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Pravastatin; Evacetrapib

Study Results

Participant Flow

Pre-assignment Detail	All participants were administered 40 milligrams (mg) Pravastatin on Day 1 (Period 1) and 130 mg Evacetrapib on Days 2 through 11 and 40 mg Pravastatin coadministered on Day 11 (Period 2).

Arm/Group Title	Pravastatin	Evacetrapib + Pravastatin
Arm/Group Description	40 mg oral dose of pravastatin was administered on Day 1.	130 mg oral dose of evacetrapib was administered once daily (QD) on Days 2 through 11 and a 40 mg oral dose of pravastatin coadministered on Day 11.
Period Title: Period 1
STARTED	24	0
Received at Least 1 Dose of Study Drug	24	0
COMPLETED	24	0
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	0	24
Received at Least 1 Dose of Study Drug	0	24
COMPLETED	0	23
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Pravastatin and Evacetrapib + Pravastatin
Arm/Group Description	40 mg oral dose of pravastatin was administered on Day 1. One hundred and thirty (130) mg oral dose of evacetrapib was administered QD on Days 2 through 11 and 40 mg oral dose of pravastatin was co-administered on Day 11.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.8 (9.0)
Sex: Female, Male (Count of Participants)
Female	15 62.5%
Male	9 37.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	24 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	10 41.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.2%
White	13 54.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	24 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Pravastatin
Time Frame	Day 1 and Day 11: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who had evaluable Cmax results at the specific time points.

Arm/Group Title	Pravastatin (Period 1)	Evacetrapib + Pravastatin (Period 2)
Arm/Group Description	40 mg oral dose of pravastatin was administered on Day 1.	130 mg oral dose of evacetrapib was administered QD on Days 2 through 11 and a 40 mg oral dose of pravastatin coadministered on Day 11.
Measure Participants	23	23
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	142 (31)	128 (43)

2. Primary Outcome

Title	PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of Pravastatin
Time Frame	Day 1 and Day 11: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose

Outcome Measure Data

Analysis Population Description

All participants who had evaluable AUC(0-∞) at the specific time points.

Arm/Group Title	Pravastatin (Period 1)	Evacetrapib + Pravastatin (Period 2)
Arm/Group Description	40 mg oral dose of pravastatin was administered on Day 1.	130 mg oral dose of evacetrapib was administered QD on Days 2 through11 and a 40 mg oral dose of pravastatin coadministered on Day 11.
Measure Participants	23	23
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours/milliliters (ng*h/mL)]	257 (27)	229 (37)

3. Primary Outcome

Title	PK: Time of Maximum Observed Concentration (Tmax) of Pravastatin
Time Frame	Day 1 and Day 11: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants with evaluable tmax results at the specific time points.

Arm/Group Title	Pravastatin (Period 1)	Evacetrapib + Pravastatin (Period 2)
Arm/Group Description	40 mg oral dose of pravastatin was administered on Day 1.	130 mg oral dose of evacetrapib was administered QD on Days 2 through 11 and a 40 mg oral dose of pravastatin coadministered on Day 11.
Measure Participants	23	23
Median (Full Range) [hours]	1.00	0.75

Adverse Events

Arm/Group Title	40 mg Pravastatin Japanese		130 mg Evacetrapib Japanese		40 mg Pravastatin + 130 mg Evacetrapib Japanese		40 mg Pravastatin Non-Japanese		130 mg Evacetrapib Non-Japanese		40 mg Pravastatin + 130-mg Evacetrapib Non-Japanese
Arm/Group Description	40 mg oral dose of pravastatin was administered on Day 1.		130 mg oral dose of evacetrapib was administered QD on Days 2 through 11 and a 40 mg oral dose of pravastatin coadministered on Day 11.		40 mg oral dose of pravastatin was administered on Day 1. 130 mg oral dose of evacetrapib was administered QD on Days 2 through11 and a 40 mg oral dose of pravastatin coadministered on Day 11.		40 mg oral dose of pravastatin was administered on Day 1.		130 mg oral dose of evacetrapib was administered QD on Days 2 through 11 and a 40 mg oral dose of pravastatin coadministered on Day 11.		40 mg oral dose of pravastatin was administered on Day 1. 130 mg oral dose of evacetrapib was administered QD on Days 2 through 11 and a 40 mg oral dose of pravastatin coadministered on Day 11.
All Cause Mortality
	40 mg Pravastatin Japanese		130 mg Evacetrapib Japanese		40 mg Pravastatin + 130 mg Evacetrapib Japanese		40 mg Pravastatin Non-Japanese		130 mg Evacetrapib Non-Japanese		40 mg Pravastatin + 130-mg Evacetrapib Non-Japanese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	40 mg Pravastatin Japanese		130 mg Evacetrapib Japanese		40 mg Pravastatin + 130 mg Evacetrapib Japanese		40 mg Pravastatin Non-Japanese		130 mg Evacetrapib Non-Japanese		40 mg Pravastatin + 130-mg Evacetrapib Non-Japanese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/14 (0%)		0/14 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	40 mg Pravastatin Japanese		130 mg Evacetrapib Japanese		40 mg Pravastatin + 130 mg Evacetrapib Japanese		40 mg Pravastatin Non-Japanese		130 mg Evacetrapib Non-Japanese		40 mg Pravastatin + 130-mg Evacetrapib Non-Japanese
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		6/10 (60%)		4/10 (40%)		4/14 (28.6%)		4/14 (28.6%)		6/13 (46.2%)
Gastrointestinal disorders
Abdominal distension	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Abdominal pain	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/13 (0%)	0
Abdominal pain lower	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Abdominal pain upper	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/14 (7.1%)	1	2/14 (14.3%)	2	2/13 (15.4%)	2
Diarrhoea	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	2/14 (14.3%)	2	0/14 (0%)	0	1/13 (7.7%)	1
Nausea	0/10 (0%)	0	2/10 (20%)	3	0/10 (0%)	0	3/14 (21.4%)	3	1/14 (7.1%)	1	1/13 (7.7%)	1
Toothache	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Vomiting	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	2/14 (14.3%)	5	0/14 (0%)	0	0/13 (0%)	0
General disorders
Fatigue	1/10 (10%)	1	0/10 (0%)	0	2/10 (20%)	2	1/14 (7.1%)	1	0/14 (0%)	0	1/13 (7.7%)	1
Feeling hot	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Infections and infestations
Nasopharyngitis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Tooth infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Injury, poisoning and procedural complications
Excoriation	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/14 (0%)	0	0/14 (0%)	0	0/13 (0%)	0
Laceration	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/13 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Increased appetite	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/13 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	2
Nervous system disorders
Dizziness	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/14 (7.1%)	1	1/14 (7.1%)	1	0/13 (0%)	0
Headache	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	2/14 (14.3%)	2	1/14 (7.1%)	1	0/13 (0%)	0
Paraesthesia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Presyncope	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Somnolence	0/10 (0%)	0	2/10 (20%)	5	1/10 (10%)	1	1/14 (7.1%)	1	0/14 (0%)	0	0/13 (0%)	0
Psychiatric disorders
Anxiety	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Nightmare	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Sleep disorder	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Rash	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.