A Study of LY2835219 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02059148
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 5.9
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

Participants in this study will receive 3 single oral doses of LY2835219 at least 14 days apart. One dose will be given with a standard meal, one dose with a high-fat meal and one dose without food. The study will evaluate the effects of the standard and high-fat meals on how much drug gets into the bloodstream. Side effects will be documented. This study is approximately 43 days, not including screening. Screening is required within 28 days prior to the start of the study.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2835219	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Food on the Pharmacokinetics of LY2835219 in Healthy Subjects
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2835219 Standard Single oral dose of LY2835219 given with a standard meal in one of three study periods.	Drug: LY2835219; Administered orally.; Other Names: abemaciclib
Experimental: LY2835219 Fasted Single oral dose of LY2835219 given with no food in one of three periods.	Drug: LY2835219; Administered orally.; Other Names: abemaciclib
Experimental: LY2835219 High-Fat Single oral dose of LY2835219 given with a high fat meal in one of three periods.	Drug: LY2835219; Administered orally.; Other Names: abemaciclib

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219 Fasted vs. High-Fat Arms [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

2. Pharmacokinetics: Area Under the Concentration Curve (0-t Last) [AUC(0-t Last)] of LY2835219 Fasted vs. High-Fat Arms [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

3. Pharmacokinetics: Time of Maximum Observed Concentration (Tmax) of LY2835219 Fasted vs. High-Fat Arms [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

Secondary Outcome Measures

1. Pharmacokinetics: Cmax of LY2835219 in Standard Meal Arm [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

2. Pharmacokinetics: AUC(0-tlast) of LY2835219 in Standard Meal Arm [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

3. Pharmacokinetics: Tmax of LY2835219 in Standard Meal Arm [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

4. Pharmacokinetics: Area Under the Concentration Curve (AUC 0-t Last) of LSN3106726 (M20) [Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period]

   Area under the concentration versus time curve from time zero to time t, where t is the last time point with a measurable concentration of LSN3106726 (M20), an active metabolite of LY2835219.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Healthy sterile males or surgically sterile or postmenopausal females

• Have a body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m^2), inclusive, at screening

• Are able to eat a high-fat, high-calorie meal

Exclusion Criteria:

• Participated in a clinical trial involving investigational product within 30 days

• Abnormal blood pressure

• 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

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

• Show evidence of human immunodeficiency virus, hepatitis B or hepatitis C

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: NCT02059148
• Other Study ID Numbers: 15175; I3Y-MC-JPBG
• First Posted: Feb 11, 2014
• Last Update Posted: Jan 7, 2019
• Last Verified: Dec 1, 2018

Study Results

Participant Flow

Arm/Group Title	Sequence 1	Sequence 2	Sequence 3	Sequence 4	Sequence 5	Sequence 6
Arm/Group Description	Single Oral Dose of 200 mg LY2835219 on 3 Occasions: Standard Meal, Fasted State, High-Fat Meal. Dosing occasions were separated by at least 14 days.	Single Oral Dose of 200 mg LY2835219 on 3 Occasions: Standard Meal, High-Fat Meal, Fasted State. Dosing occasions were separated by at least 14 days.	Single Oral Dose of 200 mg LY2835219 on 3 Occasions: Fasted State, High-Fat Meal, Standard Meal. Dosing occasions were separated by at least 14 days.	Single oral dose of 200 mg LY2835219 on 3 Occasions: Fasted State, Standard Meal, High-Fat Meal. Dosing occasions were separated by at least 14 days.	Single oral dose of 200 mg LY2835219 on 3 Occasions: High-Fat Meal, Fasted State, Standard Meal. Dosing occasions were separated by at least 14 days.	Single Oral Dose of 200 mg LY2835219 on 3 Occasions: High-Fat Meal, Standard Meal, Fasted State. Dosing occasions were separated by at least 14 days.
Period Title: Treatment 1
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	4	3
NOT COMPLETED	0	0	0	0	0	1
Period Title: Treatment 1
STARTED	4	4	4	4	4	3
COMPLETED	4	4	4	4	4	3
NOT COMPLETED	0	0	0	0	0	0
Period Title: Treatment 1
STARTED	4	4	4	4	4	3
COMPLETED	4	4	4	4	4	3
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Single Oral Dose of 200 mg LY2835219 on 3 Occasions: Standard Meal, Fasted State, High-Fat Meal. Dosing occasions were separated by at least 14 days.
Overall Participants	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.9 (9.5)
Sex: Female, Male (Count of Participants)
Female	21 87.5%
Male	3 12.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 20.8%
Not Hispanic or Latino	19 79.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 8.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	13 54.2%
White	9 37.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219 Fasted vs. High-Fat Arms
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Fasted	LY2835219 High-Fat
Arm/Group Description	Single oral dose of LY2835219 given with no food in one of three periods. LY2835219: Administered orally.	Single oral dose of LY2835219 given with a high fat meal in one of three periods. LY2835219: Administered orally.
Measure Participants	23	24
Geometric Mean (Geometric Coefficient of Variation) [nanogram/milliliter (ng/mL)]	111 (61)	137 (52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2835219 Fasted, LY2835219 High-Fat
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 90%; 1.11 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration Curve (0-t Last) [AUC(0-t Last)] of LY2835219 Fasted vs. High-Fat Arms
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Fasted	LY2835219 High-Fat
Arm/Group Description	Single oral dose of LY2835219 given with no food in one of three periods. LY2835219: Administered orally.	Single oral dose of LY2835219 given with a high fat meal in one of three periods. LY2835219: Administered orally.
Measure Participants	23	24
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour/mL (ng*h/mL)]	4160 (65)	4790 (57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2835219 Fasted, LY2835219 High-Fat
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LSMeans
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 90%; 1.05 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Pharmacokinetics: Time of Maximum Observed Concentration (Tmax) of LY2835219 Fasted vs. High-Fat Arms
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Fasted	LY2835219 High-Fat
Arm/Group Description	Single oral dose of LY2835219 given with no food in one of three periods. LY2835219: Administered orally.	Single oral dose of LY2835219 given with a high fat meal in one of three periods. LY2835219: Administered orally.
Measure Participants	23	24
Median (Full Range) [hour (h)]	8.00	10.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2835219 Fasted, LY2835219 High-Fat
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.95
	Confidence Interval	(2-Sided) 90%; 1.00 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Pharmacokinetics: Cmax of LY2835219 in Standard Meal Arm
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Standard
Arm/Group Description	Single oral dose of LY2835219 given with a standard meal in one of three study periods. LY2835219 administered orally.
Measure Participants	22
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	141 (55)

5. Secondary Outcome

Title	Pharmacokinetics: AUC(0-tlast) of LY2835219 in Standard Meal Arm
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Standard
Arm/Group Description	Single oral dose of LY2835219 given with a standard meal in one of three study periods. LY2835219 administered orally.
Measure Participants	22
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	4610 (65)

6. Secondary Outcome

Title	Pharmacokinetics: Tmax of LY2835219 in Standard Meal Arm
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Standard
Arm/Group Description	Single oral dose of LY2835219 given with a standard meal in one of three study periods. LY2835219 administered orally.
Measure Participants	22
Median (Full Range) [hour (h)]	8.00

7. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Curve (AUC 0-t Last) of LSN3106726 (M20)
Description	Area under the concentration versus time curve from time zero to time t, where t is the last time point with a measurable concentration of LSN3106726 (M20), an active metabolite of LY2835219.
Time Frame	Predose, 0.5,1,2,3,4,6,8,10,12,24,48,72,96,120,144,168,192 hours post-LY2835219 dose in each period

Outcome Measure Data

Analysis Population Description

All randomized participants receiving at least one dose of the investigational product.

Arm/Group Title	LY2835219 Standard	LY2835219 Fasted	LY2835219 High-Fat
Arm/Group Description	Single oral dose of LY2835219 given with a standard meal in one of three study periods. LY2835219: Administered orally.	Single oral dose of LY2835219 given with no food in one of three periods. LY2835219: Administered orally.	Single oral dose of LY2835219 given with a high fat meal in one of three periods. LY2835219: Administered orally.
Measure Participants	22	23	24
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	3590 (35)	3320 (40)	3510 (35)

Adverse Events

Arm/Group Title	LY2835219 Standard		LY2835219 Fasted		LY2835219 High-Fat
Arm/Group Description	Single oral dose of LY2835219 given with a standard meal in one of three study periods. LY2835219: Administered orally.		Single oral dose of LY2835219 given with no food in one of three periods. LY2835219: Administered orally.		Single oral dose of LY2835219 given with a high fat meal in one of three periods. LY2835219: Administered orally.
All Cause Mortality
	LY2835219 Standard		LY2835219 Fasted		LY2835219 High-Fat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2835219 Standard		LY2835219 Fasted		LY2835219 High-Fat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	LY2835219 Standard		LY2835219 Fasted		LY2835219 High-Fat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/23 (17.4%)		6/23 (26.1%)		4/24 (16.7%)
Gastrointestinal disorders
Diarrhoea	2/23 (8.7%)	2	0/23 (0%)	0	3/24 (12.5%)	3
Nausea	3/23 (13%)	3	3/23 (13%)	3	0/24 (0%)	0
Infections and infestations
Viral upper respiratory tract infection	0/23 (0%)	0	2/23 (8.7%)	2	1/24 (4.2%)	1
Nervous system disorders
Headache	2/23 (8.7%)	2	2/23 (8.7%)	2	0/24 (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.