A Study of LY2835219 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02256267
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 23.6

Study Details

Study Description

Brief Summary

The aim of this two-period study is to compare how much of the study drug gets into the blood stream when it is given as a single oral dose and when it is given as a single oral dose in combination with rifampin (a Food and Drug Administration [FDA] approved antibiotic that is used to treat tuberculosis, a bacterial infection that mainly affects the lungs, and other infections). Each participant will complete both study periods.

The study will last about 34 days. Screening is required within 28 days before study drug is given.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2835219; Drug: Rifampin	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: Effects of CYP3A Induction by Rifampin on the Pharmacokinetics of LY2835219 and Its Metabolites in Healthy Subjects
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2835219 Single oral dose of LY2835219	Drug: LY2835219; Administered orally; Other Names: abemaciclib
Experimental: LY2835219 + Rifampin Single oral dose of LY2835219 with rifampin orally, once daily for 14 days	Drug: LY2835219; Administered orally; Other Names: abemaciclib ; Drug: Rifampin; Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219 [Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours]

2. PK: Area Under the Concentration Time Curve AUC(0-∞) of LY2835219 [Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy sterile males or surgically sterile females or postmenopausal females

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

Exclusion Criteria:

• Have participated in a clinical trial involving investigational product within the last 30 days

• 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 an abnormal blood pressure

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

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

• Have used or intend to use over-the-counter or prescription medication including herbal medications within 7 days prior to dosing or 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: NCT02256267
• Other Study ID Numbers: 15174; I3Y-MC-JPBF
• First Posted: Oct 3, 2014
• Last Update Posted: Jan 7, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Rifampin

Study Results

Participant Flow

Pre-assignment Detail	This is an open-label, 2-period, fixed-sequence study

Arm/Group Title	LY2835219 Then LY2835219 + Rifampin
Arm/Group Description	Single oral dose of 200 milligrams (mg) LY2835219 on Day 1 in Period 1. Once daily (QD) doses of 600 mg of Rifampin for 6 days (Day 1 through Day 6) in Period 2.Single oral dose of 200 mg of LY2835219 with 600 mg Rifampin orally, QD on Day 7 in Period 2. QD doses of 600 mg Rifampin was continued for 7 days in Period 2 after coadministration with LY2835219 dose.
Period Title: Period 1 (Day 1; Day 2 to Day 9 Washout)
STARTED	24
Received at Least 1 Dose of LY2835219	24
COMPLETED	23
NOT COMPLETED	1
Period Title: Period 1 (Day 1; Day 2 to Day 9 Washout)
STARTED	23
Received at Least 1 Dose of Rifampin	23
COMPLETED	23
NOT COMPLETED	0
Period Title: Period 1 (Day 1; Day 2 to Day 9 Washout)
STARTED	23
Received LY2835219 + Rifampin	23
COMPLETED	22
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	LY2835219 Alone, Then Rifampin, Then LY2835219 + Rifampin
Arm/Group Description	Single oral dose of 200 mg LY2835219 on Day 1 in Period 1. Day 2 through Day 9 in Period 1 is washout. QD doses of 600 mg of Rifampin for 6 days (Day 1 through Day 6) in Period 2.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (7.4)
Sex: Female, Male (Count of Participants)
Female	21 87.5%
Male	3 12.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 25%
White	15 62.5%
More than one race	3 12.5%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219
Time Frame	Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and have evaluable PK data.

Arm/Group Title	200 mg LY2835219	200 mg LY2835219 + 600 mg Rifampin
Arm/Group Description	Single oral dose of 200 mg LY2835219	Single oral dose of 200 mg of LY2835219 with 600 mg rifampin orally, QD for 14 days
Measure Participants	24	21
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/ml)]	134 (45)	10.5 (58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200 mg LY2835219, 200 mg LY2835219 + 600 mg Rifampin
	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 Least Squares Means
	Estimated Value	0.0771
	Confidence Interval	(2-Sided) 90%; 0.0671 to 0.0886
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	PK: Area Under the Concentration Time Curve AUC(0-∞) of LY2835219
Time Frame	Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and have evaluable PK data.

Arm/Group Title	200 mg LY2835219	200 mg LY2835219 + 600 mg Rifampin
Arm/Group Description	Single oral dose of 200 mg LY2835219	Single oral dose of 200 mg of LY2835219 with 600 mg rifampin orally, QD for 14 days
Measure Participants	24	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram x hour per mL (ng x h/mL)]	4570 (53)	229 (48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200 mg LY2835219, 200 mg LY2835219 + 600 mg Rifampin
	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 Least Squares Means
	Estimated Value	0.0467
	Confidence Interval	(2-Sided) 90%; 0.0376 to 0.0581
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	LY2835219		Rifampin		LY2835219 + Rifampin
Arm/Group Description	Single oral dose of 200 mg LY2835219 Day 1, period 1.		Single oral, QD doses of 600 mg of Rifampin for 6 days Day 1 to Day 6 in period 2		Single oral dose of 200 mg of LY2835219 with 600 mg rifampin orally, QD on Day 7 of period 2.
All Cause Mortality
	LY2835219		Rifampin		LY2835219 + Rifampin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2835219		Rifampin		LY2835219 + Rifampin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)		1/23 (4.3%)
Nervous system disorders
Syncope	0/24 (0%)	0	0/23 (0%)	0	1/23 (4.3%)	1
Other (Not Including Serious) Adverse Events
	LY2835219		Rifampin		LY2835219 + Rifampin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/24 (33.3%)		2/23 (8.7%)		4/23 (17.4%)
Gastrointestinal disorders
Diarrhoea	2/24 (8.3%)	2	1/23 (4.3%)	1	0/23 (0%)	0
Nausea	1/24 (4.2%)	2	1/23 (4.3%)	1	3/23 (13%)	3
Infections and infestations
Upper respiratory tract infection	3/24 (12.5%)	3	1/23 (4.3%)	1	0/23 (0%)	0
Nervous system disorders
Headache	1/24 (4.2%)	1	0/23 (0%)	0	2/23 (8.7%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/24 (8.3%)	2	0/23 (0%)	0	0/23 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Research Organization (CRO) and its third party contractors shall not publish, discuss or release data emanating from a Study without Lilly's express written permission.