A Study of Evacetrapib and Digoxin in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01897493
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 7.9

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine how much digoxin gets into the blood stream and how long it takes the body to get rid of it when given with the study drug evacetrapib. This study will also look at the effect of evacetrapib on the removal of digoxin from the body by the kidneys. Information about any side effects that may occur will be collected. This study will last approximately 33 days for each participant, not including screening.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 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 Digoxin in Healthy Subjects
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Digoxin 0.5 milligram (mg) digoxin administered orally once daily (QD) on Day 1	Drug: Digoxin; Administered orally
Experimental: Evacetrapib + Digoxin 130 mg evacetrapib administered orally, QD for 14 days (Days 6 through 19) with a single oral dose of 0.5 mg digoxin coadministered on Day 15	Drug: Evacetrapib; Administered orally; Other Names: LY2484595 ; Drug: Digoxin; Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Digoxin [Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin]

2. PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of Digoxin [Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin]

3. PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin [Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin]

Secondary Outcome Measures

1. Renal Clearance (CLr) of Digoxin [Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin]

   CLr was defined as the volume of serum cleared of digoxin per unit of time after a single dose of digoxin.

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 males and females (of non-childbearing potential)

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

• Normal renal function

Exclusion Criteria:

• Participants who currently smoke or use tobacco or nicotine products

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.	Dallas	Texas	United States	75247

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: NCT01897493
• Other Study ID Numbers: 14619; I1V-MC-EIAQ
• First Posted: Jul 12, 2013
• Last Update Posted: Oct 9, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Digoxin; Evacetrapib

Study Results

Participant Flow

Arm/Group Title	Evacetrapib+Digoxin
Arm/Group Description	Period 1 (Day 1 through Day 6 predose): Participants received a single oral dose of 0.5 milligrams (mg) digoxin on Day 1 Period 2 (Day 6 postdose through Day 20): Participants received an oral dose of 130 mg evacetrapib once daily (QD) on Days 6 through 19 with single oral dose of 0.5 mg digoxin administered on Day 15
Period Title: Period 1 (Day 1 Through Day 6 Predose)
STARTED	16
Received at Least 1 Dose of Study Drug	16
COMPLETED	15
NOT COMPLETED	1
Period Title: Period 1 (Day 1 Through Day 6 Predose)
STARTED	15
Received at Least 1 Dose of Study Drug	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Evacetrapib+Digoxin
Arm/Group Description	Period 1 (Day 1 through Day 6 Predose): Participants received a single oral dose of 0.5 mg digoxin on Day 1 Period 2 (Day 6 Post-Dose through Day 20): Participants received an oral dose of 130 mg evacetrapib QD on Days 6 through 19 with a single oral dose of 0.5 mg digoxin administered on Day 15
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.6 (11.2)
Sex: Female, Male (Count of Participants)
Female	2 12.5%
Male	14 87.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 25%
Not Hispanic or Latino	12 75%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 6.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 37.5%
White	9 56.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Digoxin
Time Frame	Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin

Outcome Measure Data

Analysis Population Description

All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable Cmax data.

Arm/Group Title	Period 1-Digoxin	Period 2-Evacetrapib + Digoxin
Arm/Group Description	Digoxin: Participants received 0.5 mg digoxin administered orally QD on Day 1	Evacetrapib+Digoxin: Participants received 130 mg evacetrapib administered orally, QD for 14 days (Days 6 through 19) with a single oral dose of 0.5 mg digoxin coadministered on Day 15
Measure Participants	16	15
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	1.75 (28)	2.15 (32)

2. Primary Outcome

Title	PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-∞) of Digoxin
Time Frame	Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin

Outcome Measure Data

Analysis Population Description

All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable AUC0-∞ data.

Arm/Group Title	Period 1-Digoxin	Period 2-Evacetrapib + Digoxin
Arm/Group Description	Digoxin: Participants received 0.5 mg digoxin administered orally QD on Day 1	Evacetrapib+Digoxin: Participants received 130 mg evacetrapib administered orally, QD for 14 days (Days 6 through 19) with a single oral dose of 0.5 mg digoxin coadministered on Day 15
Measure Participants	16	15
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*h/mL)]	31.3 (18)	33.5 (26)

3. Primary Outcome

Title	PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin
Time Frame	Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin

Outcome Measure Data

Analysis Population Description

All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable tmax data.

Arm/Group Title	Period 1-Digoxin	Period 2-Evacetrapib + Digoxin
Arm/Group Description	Digoxin: Participants received 0.5 mg digoxin administered orally QD on Day 1	Evacetrapib+Digoxin: Participants received 130 mg evacetrapib administered orally, QD for 14 days (Days 6 through 19) with a single oral dose of 0.5 mg digoxin coadministered on Day 15
Measure Participants	16	15
Median (Full Range) [hours]	2.00	2.00

4. Secondary Outcome

Title	Renal Clearance (CLr) of Digoxin
Description	CLr was defined as the volume of serum cleared of digoxin per unit of time after a single dose of digoxin.
Time Frame	Periods 1 and 2: digoxin predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours after administration of digoxin

Outcome Measure Data

Analysis Population Description

All enrolled participants who received digoxin in Periods 1 and 2 and had evaluable CLr data.

Arm/Group Title	Period 1-Digoxin	Period 2-Evacetrapib + Digoxin
Arm/Group Description	Digoxin: Participants received 0.5 mg digoxin administered orally QD on Day 1	Evacetrapib+Digoxin: Participants received 130 mg evacetrapib administered orally, QD for 14 days (Days 6 through 19) with a single oral dose of 0.5 mg digoxin coadministered on Day 15
Measure Participants	16	15
Geometric Mean (Geometric Coefficient of Variation) [liters/hour (L/h)]	9.43 (14)	8.10 (18)

Adverse Events

Arm/Group Title	Digoxin		Evacetrapib		Evacetrapib + Digoxin
Arm/Group Description	Digoxin: Participants received a single dose of 0.5 mg digoxin administered orally on Day 1. Adverse events (AEs) are reported through predose on Day 6		Evacetrapib: Participants received 130 mg evacetrapib administered orally, alone, QD for Days 6 up to 15. AEs are reported from post-dose on Day 6 through predose of Digoxin on Day 15.		Evacetrapib+Digoxin: Participants received 130 mg evacetrapib administered orally, QD for 14 days (Days 6 to 19) with a single oral dose of 0.5 mg digoxin coadministered on Day 15. AEs are reported from post-dose on Day 15 up to Day 33.
All Cause Mortality
	Digoxin		Evacetrapib		Evacetrapib + Digoxin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Digoxin		Evacetrapib		Evacetrapib + Digoxin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Digoxin		Evacetrapib		Evacetrapib + Digoxin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		1/15 (6.7%)		1/15 (6.7%)
Infections and infestations
Rhinitis	1/16 (6.3%)	1	0/15 (0%)	0	0/15 (0%)	0
Nervous system disorders
Headache	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (0%)	0
Skin and subcutaneous tissue disorders
Dry skin	0/16 (0%)	0	0/15 (0%)	0	1/15 (6.7%)	1
Pruritus	0/16 (0%)	0	1/15 (6.7%)	1	0/15 (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.