A Study of Evacetrapib in Healthy Female Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01746732
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of evacetrapib on oral contraceptives (Ortho-Cyclen®) when given to healthy female participants. The amount of female hormones found in the blood will be measured and compared when taken alone and when taken with evaceptrapib. Each woman will participate in two study periods. Information about any side effects that may occur will also be collected.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Ortho-Cyclen; Drug: Evacetrapib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of Evacetrapib (LY2484595) on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ortho-Cyclen Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Treatment A	Drug: Ortho-Cyclen; Oral administration
Experimental: Ortho-Cyclen + Evacetrapib Ortho-Cyclen administered orally, QD, for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally, QD, for 21 days (Days 1 to 21) in one of two treatment periods. Treatment B	Drug: Ortho-Cyclen; Oral administration; Drug: Evacetrapib; Oral administration; Other Names: LY2484595

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

2. PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Ethinyl Estradiol [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

3. PK: Minimum Observed Drug Concentration (Cmin) of Ethinyl Estradiol [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

4. PK: Time of Maximum Observed Drug Concentration (Tmax) of Ethinyl Estradiol [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

5. PK: Maximum Concentration (Cmax) of Norelgestromin [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

6. PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Norelgestromin [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

7. PK: Minimum Observed Drug Concentration (Cmin) of Norelgestromin [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

8. PK: Time of Maximum Observed Drug Concentration (Tmax) of Norelgestromin [Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Are pre-menopausal females, and who are healthy as determined by medical history and physical examination

• Have a body mass index of 18 to 30 kilograms per square meter (kg/m^2)

Exclusion Criteria:

• Have known allergies to evacetrapib and Ortho-Cyclen (ethinyl estradiol and norgestimate), related compounds or any components of the formulation

• Have a clinically significant 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

• Have taken injectable contraceptives within 12 months prior to the first dose of the lead-in period or topical controlled delivery contraceptives (patch) for 3 months prior to the first dose of the lead-in period

• Use of any tobacco- or nicotine-containing products within 6 months prior to the lead-in phase and during the study

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: NCT01746732
• Other Study ID Numbers: 14617; I1V-MC-EIAP
• First Posted: Dec 11, 2012
• Last Update Posted: Oct 9, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Moxifloxacin; Evacetrapib; Norgestimate, ethinyl estradiol drug combination

Study Results

Participant Flow

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen Then Ortho-Cyclen + Evacetrapib; Sequence AB	Ortho-Cyclen + Evacetrapib Then Ortho-Cyclen; Sequence BA
Arm/Group Description	Ortho-Cyclen (OC) of (35 microgram [mcg] ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD) for 28 days (Days 1 to 28)	Treatment A OC administered orally, QD for 28 days (Days 1 to 28) Treatment B OC administered orally, QD for 28 days (Days 1 to 28) and 130 milligram (mg) Evacetrapib orally, QD for 21 days (Days 1 to 21)	Treatment B OC administered orally, QD for 28 days (Days 1 to 28) and 130 mg Evacetrapib orally, QD for 21 days (Days 1 to 21) Treatment A OC administered orally, QD for 28 days (Days 1 to 28)
Period Title: Lead-In Period
STARTED	23	0	0
Participants Received at Least 1 Dose	22	0	0
COMPLETED	22	0	0
NOT COMPLETED	1	0	0
Period Title: Lead-In Period
STARTED	0	11	11
COMPLETED	0	10	11
NOT COMPLETED	0	1	0
Period Title: Lead-In Period
STARTED	0	10	11
COMPLETED	0	10	7
NOT COMPLETED	0	0	4

Baseline Characteristics

Arm/Group Title	Ortho-Cyclen and Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, QD for 28 days (lead-in period). Treatment A Ortho-Cyclen administered orally, QD for 28 Days (Days 1 to 28) Treatment B Ortho-Cyclen orally, QD for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally, QD for 21 days (Days 1 to 21)
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.0 (6.8)
Sex/Gender, Customized (Number) [Number]
Females	22 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 36.4%
Not Hispanic or Latino	14 63.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 36.4%
White	11 50%
More than one race	2 9.1%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ethinyl Estradiol
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, once daily (QD) for 28 days (Days 1 to 28) and 130 mg Evacetrapib orally, once daily (QD) for 21 days (Days 1 to 21)
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [picogram per milliliter (pg/ml)]	71.7 (35)	70.6 (37)

2. Primary Outcome

Title	PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Ethinyl Estradiol
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, QD, for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally, QD, for 21 days (Days 1 to 21) in one of two treatment periods. Ortho-Cyclen: Oral administration Evacetrapib: Oral administration
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [picogram x hour per ml (pg*hour/ml)]	907 (31)	840 (28)

3. Primary Outcome

Title	PK: Minimum Observed Drug Concentration (Cmin) of Ethinyl Estradiol
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, QD, for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally, QD, for 21 days (Days 1 to 21) in one of two treatment periods. Ortho-Cyclen: Oral administration Evacetrapib: Oral administration
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [pg/ml]	15.9 (65)	13.2 (66)

4. Primary Outcome

Title	PK: Time of Maximum Observed Drug Concentration (Tmax) of Ethinyl Estradiol
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, QD, for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally, QD, for 21 days (Days 1 to 21) in one of two treatment periods. Ortho-Cyclen: Oral administration Evacetrapib: Oral administration
Measure Participants	16	17
Median (Full Range) [hour]	3.00	4.00

5. Primary Outcome

Title	PK: Maximum Concentration (Cmax) of Norelgestromin
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, once daily (QD) for 28 days (Days 1 to 28) and 130 mg Evacetrapib orally, once daily (QD) for 21 days (Days 1 to 21)
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [pg/ml]	1410 (21)	1830 (17)

6. Primary Outcome

Title	PK: Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Norelgestromin
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, once daily (QD) for 28 days (Days 1 to 28) and 130 mg Evacetrapib orally, once daily (QD) for 21 days (Days 1 to 21)
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [pg*hour/ml]	16200 (21)	18100 (22)

7. Primary Outcome

Title	PK: Minimum Observed Drug Concentration (Cmin) of Norelgestromin
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, once daily (QD) for 28 days (Days 1 to 28) and 130 mg Evacetrapib orally, once daily (QD) for 21 days (Days 1 to 21)
Measure Participants	16	17
Geometric Mean (Geometric Coefficient of Variation) [pg/ml]	397 (35)	422 (34)

8. Primary Outcome

Title	PK: Time of Maximum Observed Drug Concentration (Tmax) of Norelgestromin
Time Frame	Day 21: Predose, 0.5,1,1.5,2,3,4,5,6,8,10,12,16 and 24 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ortho-Cyclen	Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily (QD), for 28 days (lead-in period). Then, Ortho-Cyclen orally QD for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration	Ortho-Cyclen administered orally, once daily (QD) for 28 days (Days 1 to 28) and 130 mg Evacetrapib orally, once daily (QD) for 21 days (Days 1 to 21)
Measure Participants	16	17
Median (Full Range) [hour]	3.53	4.00

Adverse Events

Arm/Group Title	Ortho-Cyclen (Lead-in Phase)		Ortho-Cyclen		Ortho-Cyclen + Evacetrapib
Arm/Group Description	Ortho-Cyclen oral doses of (35 mcg ethinyl estradiol and 250 mcg norgestimate) once daily for 28 days (Days 1 to 28)		Ortho-Cyclen (35 microgram (mcg) ethinyl estradiol and 250 mcg norgestimate) administered orally, once daily for 28 days (lead-in period). Then, Ortho-Cyclen orally for 28 Days (Days 1 to 28) in one of two treatment periods. Ortho-Cyclen: Oral administration		Ortho-Cyclen administered orally for 28 days (lead-in period). Then, Ortho-Cyclen orally for 28 Days (Days 1 to 28) and 130 mg evacetrapib orally for 21 days (Days 1 to 21) in one of two treatment periods. Ortho-Cyclen: Oral administration Evacetrapib: Oral administration
All Cause Mortality
	Ortho-Cyclen (Lead-in Phase)		Ortho-Cyclen		Ortho-Cyclen + Evacetrapib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ortho-Cyclen (Lead-in Phase)		Ortho-Cyclen		Ortho-Cyclen + Evacetrapib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/17 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Ortho-Cyclen (Lead-in Phase)		Ortho-Cyclen		Ortho-Cyclen + Evacetrapib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/22 (40.9%)		5/17 (29.4%)		5/21 (23.8%)
Gastrointestinal disorders
Nausea	1/22 (4.5%)	1	2/17 (11.8%)	2	1/21 (4.8%)	1
Injury, poisoning and procedural complications
Procedural dizziness	0/22 (0%)	0	1/17 (5.9%)	1	0/21 (0%)	0
Nervous system disorders
Dizziness	2/22 (9.1%)	2	0/17 (0%)	0	0/21 (0%)	0
Headache	8/22 (36.4%)	9	1/17 (5.9%)	1	5/21 (23.8%)	5
Reproductive system and breast disorders
Menstruation irregular	1/22 (4.5%)	1	1/17 (5.9%)	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.