A Study of Two Dosage Forms of LY2886721 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01775904
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 4
• Duration (Months): 2.9
• Patients Per Site Per Month: 8.9

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate two different formulations of LY2886721. In addition, this study will determine how much of study drug (LY2886721) gets into the blood steam and how long the body takes to get rid of it after taking each formulation with or without a meal. Information about any side effects that may occur will also be collected. Each participant may be involved in the study for approximately 7 weeks.

This study requires 4 periods. In each period, participants will receive LY2886721 as a tablet or capsule, with or without food and water. There is a 7 day washout between each period.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2886721 in a Capsule; Drug: LY2886721 in an orally disintegrating tablet (ODT)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Comparison Study of Capsule and Orally Disintegrating Tablet and to Determine the Effect of Food and Water on the Pharmacokinetics of LY2886721 in Healthy Subjects
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2886721 Capsule (water, fasting) Reference formulation. A single oral dose of 70 milligrams (mg) LY2886721 in a capsule given with water and without a meal in one of four periods.	Drug: LY2886721 in a Capsule; Administered orally.
Experimental: LY2886721 ODT (no water, fasting) A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given without water and without a meal in one of four periods.	Drug: LY2886721 in an orally disintegrating tablet (ODT); Administered orally.
Experimental: LY2886721 ODT (water, fed) A single oral dose of a 70 mg LY2886721 in an orally disintegrating tablet (ODT) given with water and after a high-fat breakfast in one of four periods.	Drug: LY2886721 in an orally disintegrating tablet (ODT); Administered orally.
Experimental: LY2886721 ODT (water, fasting) A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given with water and without a meal in one of four periods.	Drug: LY2886721 in an orally disintegrating tablet (ODT); Administered orally.

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY2886721 [Baseline through 96 hours post-dose]

2. Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of LY2886721 [Baseline through 96 hours post-dose]

3. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC[0-tlast]) of LY2886721 [Baseline through 96 hours post-dose]

4. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] of LY2886721 [Baseline through 96 hours post-dose]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a body mass index (BMI) of 18.5 to 32.0 kilograms per square meter (kg/m^2), inclusive, at screening

• At least 4 participants who are greater than 55 years of age

• Male participants: Agree to use a reliable method of birth control and not donate sperm during the study and for 3 months following the last dose of the investigational product

• Female participants: Women not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy, hysterectomy, or both) confirmed by medical history, or postmenopausal females, as determined by medical history and physical examination (spontaneous amenorrhea for 6 to 12 months and a follicle stimulating hormone [FSH] level greater than 40 milli-international units per milliliter [mIU/mL])

• Have venous access sufficient to allow for blood sampling as per the protocol

Exclusion Criteria:

• Are currently enrolled in, have completed, or discontinued within the last 30 days from a clinical trial involving an investigational product; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

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

• Have known allergies to LY2886721, related compounds, or any components of the formulation

• Have an abnormality in the 12-lead electrocardiogram (ECG)

• Have a significantly abnormal blood pressure as determined by the investigator

• Have a history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data

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

• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies

• Show evidence of hepatitis B or C and/or positive hepatitis B or C antibody

• Have a history of, or current, significant ophthalmologic disease

• Show evidence of significant active neuropsychiatric disease or history of suicide attempt

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.	Madison	Wisconsin	United States	53704

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: NCT01775904
• Other Study ID Numbers: 14249; I4O-MC-BACG
• First Posted: Jan 25, 2013
• Last Update Posted: Jul 19, 2019
• Last Verified: May 1, 2019

Study Results

Participant Flow

Arm/Group Title	Total Study Population
Arm/Group Description	All participants who entered the study and received at least 1 dose of study drug.
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	26
Received at Least One Dose of Drug	26
COMPLETED	26
NOT COMPLETED	0
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	26
COMPLETED	26
NOT COMPLETED	0
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	26
Received at Least One Dose of Drug	26
COMPLETED	25
NOT COMPLETED	1
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	25
COMPLETED	25
NOT COMPLETED	0
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	25
Received at Least One Dose of Drug	25
COMPLETED	25
NOT COMPLETED	0
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	25
COMPLETED	25
NOT COMPLETED	0
Period Title: LY2886721 ODT (no Water, Fasting)
STARTED	25
Received at Least One Dose of Drug	24
COMPLETED	24
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	All participants who entered the study and received at least 1 dose of study drug.
Overall Participants	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (17.3)
Sex: Female, Male (Count of Participants)
Female	3 11.5%
Male	23 88.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 11.5%
Not Hispanic or Latino	23 88.5%
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	5 19.2%
White	21 80.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	26 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY2886721
Time Frame	Baseline through 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with evaluable LY2886721 Cmax data.

Arm/Group Title	LY2886721 Capsule (Water, Fasting)	LY2886721 ODT (no Water, Fasting)	LY2886721 ODT (Water, Fed)	LY2886721 ODT (Water, Fasting)
Arm/Group Description	A single oral dose of 70 milligrams (mg) LY2886721 in a capsule given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given without water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and after a high-fat breakfast in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.
Measure Participants	26	26	25	24
Geometric Mean (Geometric Coefficient of Variation) [nanograms / milliliter (ng/mL)]	183 (46)	195 (29)	181 (18)	173 (37)

2. Primary Outcome

Title	Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of LY2886721
Time Frame	Baseline through 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with evaluable LY2886721 tmax data.

Arm/Group Title	LY2886721 Capsule (Water, Fasting)	LY2886721 ODT (no Water, Fasting)	LY2886721 ODT (Water, Fed)	LY2886721 ODT (Water, Fasting)
Arm/Group Description	A single oral dose of 70 milligrams (mg) LY2886721 in a capsule given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given without water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and after a high-fat breakfast in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.
Measure Participants	26	26	25	24
Median (Full Range) [hours]	3.00	2.00	4.00	2.00

3. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC[0-tlast]) of LY2886721
Time Frame	Baseline through 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with evaluable LY2886721 AUC (0-tlast) data.

Arm/Group Title	LY2886721 Capsule (Water, Fasting)	LY2886721 ODT (no Water, Fasting)	LY2886721 ODT (Water, Fed)	LY2886721 ODT (Water, Fasting)
Arm/Group Description	A single oral dose of 70 milligrams (mg) LY2886721 in a capsule given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given without water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and after a high-fat breakfast in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.
Measure Participants	26	26	25	24
Geometric Mean (Geometric Coefficient of Variation) [nanograms * hour / milliliter]	2300 (24)	2380 (19)	2480 (19)	2270 (18)

4. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] of LY2886721
Time Frame	Baseline through 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug with evaluable LY2886721 AUC (0-∞) data.

Arm/Group Title	LY2886721 Capsule (Water, Fasting)	LY2886721 ODT (no Water, Fasting)	LY2886721 ODT (Water, Fed)	LY2886721 ODT (Water, Fasting)
Arm/Group Description	A single oral dose of 70 milligrams (mg) LY2886721 in a capsule given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given without water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and after a high-fat breakfast in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.	A single oral dose of 70 mg LY2886721 in an ODT given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.
Measure Participants	26	26	25	24
Geometric Mean (Geometric Coefficient of Variation) [nanograms * hour / milliliter]	2320 (24)	2390 (19)	2490 (19)	2290 (18)

Adverse Events

Arm/Group Title	LY2886721 Capsule (Water, Fasting)		LY2886721 ODT (no Water, Fasting)		LY2886721 ODT (Water, Fed)		LY2886721 ODT (Water, Fasting)
Arm/Group Description	A single oral dose of 70 milligrams (mg) LY2886721 in a capsule given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.		A single oral dose of 70 mg LY2886721 in an orally disintegrating tablet (ODT) given without water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.		A single oral dose of 70 mg LY2886721 in an ODT given with water and after a high-fat breakfast in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.		A single oral dose of 70 mg LY2886721 in an ODT given with water and without a meal in one of four periods. Participants received a dose on the morning of Day 1 in each period. Participants were discharged on Day 5 of each period after study assessment. There was a washout period of at least 7 days between dosing in consecutive periods.
All Cause Mortality
	LY2886721 Capsule (Water, Fasting)		LY2886721 ODT (no Water, Fasting)		LY2886721 ODT (Water, Fed)		LY2886721 ODT (Water, Fasting)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2886721 Capsule (Water, Fasting)		LY2886721 ODT (no Water, Fasting)		LY2886721 ODT (Water, Fed)		LY2886721 ODT (Water, Fasting)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)		0/25 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	LY2886721 Capsule (Water, Fasting)		LY2886721 ODT (no Water, Fasting)		LY2886721 ODT (Water, Fed)		LY2886721 ODT (Water, Fasting)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/26 (34.6%)		8/26 (30.8%)		6/25 (24%)		7/24 (29.2%)
Eye disorders
Vision blurred	0/26 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Lip swelling	0/26 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0	0/24 (0%)	0
Nausea	1/26 (3.8%)	1	0/26 (0%)	0	0/25 (0%)	0	0/24 (0%)	0
Vomiting	1/26 (3.8%)	2	0/26 (0%)	0	0/25 (0%)	0	0/24 (0%)	0
General disorders
Application site discolouration	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1
Application site erythema	4/26 (15.4%)	4	2/26 (7.7%)	2	1/25 (4%)	1	2/24 (8.3%)	2
Application site irritation	0/26 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0	0/24 (0%)	0
Vessel puncture site haemorrhage	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1
Infections and infestations
Folliculitis	0/26 (0%)	0	2/26 (7.7%)	2	0/25 (0%)	0	0/24 (0%)	0
Injury, poisoning and procedural complications
Animal bite	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1
Arthropod bite	1/26 (3.8%)	1	0/26 (0%)	0	0/25 (0%)	0	0/24 (0%)	0
Excoriation	1/26 (3.8%)	1	0/26 (0%)	0	1/25 (4%)	1	0/24 (0%)	0
Ligament sprain	1/26 (3.8%)	1	0/26 (0%)	0	0/25 (0%)	0	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/26 (7.7%)	2	0/26 (0%)	0	1/25 (4%)	1	0/24 (0%)	0
Musculoskeletal discomfort	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1
Scoliosis	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1
Nervous system disorders
Headache	0/26 (0%)	0	0/26 (0%)	0	1/25 (4%)	1	0/24 (0%)	0
Migraine	1/26 (3.8%)	1	0/26 (0%)	0	0/25 (0%)	0	0/24 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/26 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0	0/24 (0%)	0
Cough	0/26 (0%)	0	0/26 (0%)	0	1/25 (4%)	1	0/24 (0%)	0
Oropharyngeal pain	0/26 (0%)	0	1/26 (3.8%)	1	1/25 (4%)	1	0/24 (0%)	0
Respiratory tract congestion	0/26 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0	0/24 (0%)	0
Sinus congestion	1/26 (3.8%)	1	1/26 (3.8%)	1	1/25 (4%)	1	0/24 (0%)	0
Skin and subcutaneous tissue disorders
Ecchymosis	0/26 (0%)	0	1/26 (3.8%)	1	0/25 (0%)	0	0/24 (0%)	0
Erythema	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	1
Rash pruritic	0/26 (0%)	0	0/26 (0%)	0	0/25 (0%)	0	1/24 (4.2%)	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.