A Study of LY2835219 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02327143
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 10.8

Study Details

Study Description

Brief Summary

The aim of this 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 as an intravenous infusion (given directly into a vein via a small needle).

The study will also provide information on how well the study drug is tolerated when given as a capsule in combination with giving it intravenously, and information on any changes in heart function.

The study will last about 10 days. Screening is required within 28 days before study drug is given.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2835219; Drug: ¹³C₈-LY2835219	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Absolute Bioavailability Study of LY2835219 in Healthy Subjects Using the Intravenous Tracer Method
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 200 mg LY2835219 200 mg LY2835219 administered orally on day 1.	Drug: LY2835219; Administered orally
Experimental: 0.4 mg ¹³C₈-LY2835219 0.4 mg ¹³C₈-LY2835219 given intravenously (IV) for 15 minutes, starting approximately 6 hours after the oral dose.	Drug: ¹³C₈-LY2835219; Administered IV

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-∞)] of LY2835219 and ¹³C₈-LY2835219 [Predose, 2, 4, 6, 6.25, 6.5, 6.75, 7.25, 8.25,10, 12, 14, 24, 48, 72, 96,120, 144, 168,192 Hours Postdose]

Secondary Outcome Measures

1. PK: Maximum Observed Concentration (Cmax) of LY2835219 [Predose, 2, 4, 6, 6.25, 6.5, 6.75, 7.25, 8.25,10, 12, 14, 24, 48, 72, 96,120, 144, 168,192 Hours Postdose]

2. PK: Time of Maximum Observed Drug Concentration (Tmax) of LY2835219 [Predose, 2, 4, 6, 6.25, 6.5, 6.75, 7.25, 8.25,10, 12, 14, 24, 48, 72, 96,120, 144, 168,192 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 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)

• Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site.

• Participants who are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

• Have participated in a clinical trial involving investigational product within the last 90 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 consumed any sensitive CYP2B6 substrate drugs, any CYP3A4 inhibitor or any CYP3A inducer, herbal supplements, grapefruits or grapefruit containing products, Seville oranges or Seville orange containing products, star fruits or star fruit containing products within 2 weeks prior to dosing or intend to consume during the study

• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening

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		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: NCT02327143
• Other Study ID Numbers: 15533; I3Y-MC-JPBS
• First Posted: Dec 30, 2014
• Last Update Posted: Aug 6, 2018
• Last Verified: Oct 1, 2017

Study Results

Participant Flow

Pre-assignment Detail	This is a single arm study. Participants first received 200 mg LY2835219 and then 0.4 mg ¹³C₈-LY2835219 given 6 hours later.

Arm/Group Title	200 mg LY2835219	200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
Arm/Group Description	200 mg LY2835219 administered orally on day 1.	0.4 mg ¹³C₈-LY2835219 given intravenously (IV) for 15 minutes, starting approximately 6 hours after the oral dose on day 1.
Period Title: Day 1: Time 0 Hrs to 6 Hrs
STARTED	11	0
COMPLETED	11	0
NOT COMPLETED	0	0
Period Title: Day 1: Time 0 Hrs to 6 Hrs
STARTED	0	11
COMPLETED	0	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	200 mg LY2835219 administered orally on day 1. 0.4 mg ¹³C₈-LY2835219 given intravenously (IV) for 15 minutes, starting approximately 6 hours after the oral dose on day 1.
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.00 (8.00)
Sex: Female, Male (Count of Participants)
Female	3 27.3%
Male	8 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 100%
Unknown or Not Reported	0 0%
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	1 9.1%
White	10 90.9%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	11 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-∞)] of LY2835219 and ¹³C₈-LY2835219
Time Frame	Predose, 2, 4, 6, 6.25, 6.5, 6.75, 7.25, 8.25,10, 12, 14, 24, 48, 72, 96,120, 144, 168,192 Hours Postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	200 mg LY2835219	200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
Arm/Group Description	200 mg LY2835219 administered orally on day 1.	0.4 mg ¹³C₈-LY2835219 given intravenously (IV) for 15 minutes, starting approximately 6 hours after the oral dose.
Measure Participants	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram*h/milliliter (ng∙h/mL)]	3730 (31)	15.4 (28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	200 mg LY2835219, 200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
	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
	Estimated Value	0.448
	Confidence Interval	(2-Sided) 90%; 0.395 to 0.508
	Parameter Dispersion	Type: Value:
	Estimation Comments	Absolute bioavailability of LY2835219 following the administration of 200 mg LY2835219 (oral) with 0.4 mg [13C8]-LY2835219 (IV).

2. Secondary Outcome

Title	PK: Maximum Observed Concentration (Cmax) of LY2835219
Time Frame	Predose, 2, 4, 6, 6.25, 6.5, 6.75, 7.25, 8.25,10, 12, 14, 24, 48, 72, 96,120, 144, 168,192 Hours Postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	200 mg LY2835219
Arm/Group Description	200 mg LY2835219 administered orally on day 1.
Measure Participants	8
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	114 (32)

3. Secondary Outcome

Title	PK: Time of Maximum Observed Drug Concentration (Tmax) of LY2835219
Time Frame	Predose, 2, 4, 6, 6.25, 6.5, 6.75, 7.25, 8.25,10, 12, 14, 24, 48, 72, 96,120, 144, 168,192 Hours Postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	200 mg LY2835219
Arm/Group Description	200 mg LY2835219 administered orally on day 1.
Measure Participants	8
Median (Full Range) [hours]	6.63

Adverse Events

Arm/Group Title	200 mg LY2835219		200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
Arm/Group Description	200 mg LY2835219 administered orally on day 1.		0.4 mg ¹³C₈-LY2835219 given intravenously (IV) for 15 minutes, starting approximately 6 hours after the oral dose.
All Cause Mortality
	200 mg LY2835219		200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	200 mg LY2835219		200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	200 mg LY2835219		200 mg LY2835219 + 0.4 mg ¹³C₈-LY2835219
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		5/11 (45.5%)
Gastrointestinal disorders
Abdominal pain upper	0/11 (0%)	0	1/11 (9.1%)	1
Constipation	0/11 (0%)	0	3/11 (27.3%)	3
Dry mouth	0/11 (0%)	0	1/11 (9.1%)	1
Dyspepsia	0/11 (0%)	0	1/11 (9.1%)	1
Nausea	1/11 (9.1%)	1	0/11 (0%)	0
Vomiting	1/11 (9.1%)	1	2/11 (18.2%)	2
General disorders
Feeling cold	0/11 (0%)	0	1/11 (9.1%)	1
Metabolism and nutrition disorders
Decreased appetite	1/11 (9.1%)	1	0/11 (0%)	0
Nervous system disorders
Dizziness	0/11 (0%)	0	1/11 (9.1%)	1
Headache	2/11 (18.2%)	2	1/11 (9.1%)	1

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.