A Study of LY2409021 Formulations and the Effect of Food

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01354496
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 6
• Duration (Months): 6
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

The purposes of this study are to compare how much of LY2409021 enters the bloodstream and how long the body takes to get rid of the drug when different formulations of LY2409021 are given, and when LY2409021 is taken with or without food.

The study will be conducted in 2 cohorts. Each cohort will have 3 study periods consisting of 3 formulations of LY2409021. Participants in each cohort will receive the same all 3 formulations using a randomized sequence crossover design. There is a washout period of at least 14 days between dosing periods.

There will be an interim analysis after Cohort 1 completes study Period 2. Cohort 2 will not begin enrolling until this analysis is complete. The need to enroll Cohort 2 will be determined by the outcome of the interim analysis.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2409021 Reference Form; Drug: LY2409021 Test-Med Formulation (medium particle size); Drug: LY2409021 Test-High Formulation (high particle size); Drug: LY2409021 Test-Low Formulation (low particle size)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: LY2409021 Formulation Bridging and Food Effect Study
• Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 - LY2409021 reference form A 20 milligram (mg) LY2409021 dose, reference form administered orally in the fasted state	Drug: LY2409021 Reference Form; Administered orally
Experimental: Cohort 1 - LY2409021 medium test form fed Single 20 mg LY2409021 test form with medium particle size administered orally immediately after ingestion of a standardized high-fat meal	Drug: LY2409021 Test-Med Formulation (medium particle size); Administered orally
Experimental: Cohort 1 - LY2409021 medium test form fasted Single 20 mg LY2409021 test form with medium particle size administered orally in the fasted state	Drug: LY2409021 Test-Med Formulation (medium particle size); Administered orally
Experimental: Cohort 2 - LY2409021 low test form fasted Single 20 mg LY2409021 test form with low particle size administered orally in the fasted state	Drug: LY2409021 Test-Low Formulation (low particle size); Administered orally
Experimental: Cohort 2 - LY2409021 medium test form fasted Single 20 mg LY2409021 test form with medium particle size administered orally in the fasted state	Drug: LY2409021 Test-Med Formulation (medium particle size); Administered orally
Experimental: Cohort 2 - LY2409021 high test form fasted Single 20 mg LY2409021 test form with high particle size administered orally in the fasted state	Drug: LY2409021 Test-High Formulation (high particle size); Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Medium Test Form to Reference Form [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

   AUC from time 0 to infinity (AUC0-∞).

2. Pharmacokinetics, Maximum Concentration (Cmax): Medium Test Form to Reference Form [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

Secondary Outcome Measures

1. Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Standardized High Fat Meal to Fasting [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

   AUC from time 0 to infinity (AUC0-∞).

2. Pharmacokinetics, Maximum Concentration (Cmax): Standardized High Fat Meal to Fasting [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

3. Pharmacokinetics, Time to Maximum Concentration (Tmax) [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

4. Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

   AUC from time 0 to infinity (AUC0-∞).

5. Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size [Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Must be healthy male or a healthy female who cannot become pregnant

• Must have body mass index (BMI) of 18.5 to 32 kilograms per meter squared (kg/m²), inclusive

• Blood pressure as well as blood and urine laboratory test results must be acceptable for the study

• The veins must be suitable for easy blood collection

• Must be willing to be available for the whole study and be willing to follow study procedures

Exclusion Criteria:

• Were in another new drug or medical research study in the last 30 days

• Have previously taken part in this study or any other study with LY2409021

• Have taken LY2409021, or drugs similar to LY2409021 before and was found to be allergic to the drug

• Currently have or used to have health problems or laboratory test results that in the opinion of the doctor, could interfere with understanding the results of this study

• Electrocardiogram (ECG) readings are not suitable for the study

• Are infected with hepatitis B

• Are infected with human immunodeficiency disease virus (HIV)

• Are using or intend to use over-the-counter medication or prescription medications within 14 days, from the start of the first study dosing until end of study

• Have a regular alcohol intake greater than 21 units per week (males) and 14 units per week (females) or are not willing to abstain from alcohol while in the research unit

• Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic

• Have a history of drug or alcohol abuse

• Have donated 450 milliliters (mL) or more of blood in the last 3 months

• Are unwilling or unable to comply with dietary requirements/restrictions during the study

• The study doctor thinks the participant should not participate for any other reasons

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 person physician.	Singapore		Singapore

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: NCT01354496
• Other Study ID Numbers: 14194; I1R-FW-GLBQ
• First Posted: May 17, 2011
• Last Update Posted: Mar 11, 2019
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Eli Lilly and Company: Healthy Volunteers; Bioavailability

Study Results

Participant Flow

Arm/Group Title	LY2409021 Cohort 1: Sequence 1	LY2409021 Cohort 1: Sequence 2	LY2409021 Cohort 1: Sequence 3	LY2409021 Cohort 2: Sequence 4	LY2409021 Cohort 2: Sequence 5	LY2409021 Cohort 2: Sequence 6
Arm/Group Description	Sequence 1: (Period 1:reference capsules fasting, then Period 2: test-medium tablet fasting, then Period 3: test-medium tablet after high-fat meal). There was a washout period of at least 14 days between interventions. Description of interventions: reference capsules fasting [20-milligram (mg) LY2409021 dose, administered orally, once in fasted state], test-medium tablet fasting (20-mg LY2409021 tablet, medium particle size, administered orally, once in fasted state), and test-medium tablet after high-fat meal (20-mg LY2409021 tablet, medium particle size, administered orally, once, immediately after standardized high-fat meal).	Sequence 2: (Period 1: test-medium tablet fasting, then Period 2: test-medium tablet after high-fat meal, then Period 3: reference capsules fasting). There was a washout period of at least 14 days between interventions. Description of interventions: reference capsules fasting [20-milligram (mg) LY2409021 dose, administered orally, once in fasted state], test-medium tablet fasting (20-mg LY2409021 tablet, medium particle size, administered orally, once in fasted state), and test-medium tablet after high-fat meal (20-mg LY2409021 tablet, medium particle size, administered orally, once, immediately after standardized high-fat meal).	Sequence 3: (Period 1:test-medium tablet after high-fat meal, then Period 2: reference capsules fasting, then Period 3: test-medium tablet fasting). There was a washout period of at least 14 days between interventions. Description of interventions: reference capsules fasting [20-milligram (mg) LY2409021 dose, administered orally, once in fasted state], test-medium tablet fasting (20-mg LY2409021 tablet, medium particle size, administered orally, once in fasted state), and test-medium tablet after high-fat meal (20-mg LY2409021 tablet, medium particle size, administered orally, once, immediately after standardized high-fat meal).	Sequence 4: (Period 1: test-medium tablet fasting then, Period 2: test-high tablet fasting, then Period 3: test-low tablet fasting) There was a washout period of at least 14 days between interventions. Description of interventions: test-low tablet fasting (single 20-mg LY2409021 tablet of a low particle size, administered orally in a fasted state), test-medium tablet fasting (single 20-mg LY2409021 tablet of a medium particle size, administered orally, once in a fasted state), and test-high tablet fasting (single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state).	Sequence 5: (Period 1: test-high tablet fasting then, Period 2: test-low tablet fasting, then Period 3: test-medium tablet fasting) There was a washout period of at least 14 days between interventions. Description of interventions: test-low tablet fasting (single 20-mg LY2409021 tablet of a low particle size, administered orally in a fasted state), test-medium tablet fasting (single 20-mg LY2409021 tablet of a medium particle size, administered orally, once in a fasted state), and test-high tablet fasting (single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state).	Sequence 6: (Period1: test-low tablet fasting, then Period 2: test-medium tablet fasting, then Period 3: test-high tablet fasting). There was a washout period of at least 14 days between interventions. Description of interventions: test-low tablet fasting (single 20-mg LY2409021 tablet of a low particle size, administered orally in a fasted state), test-medium tablet fasting (single 20-mg LY2409021 tablet of a medium particle size, administered orally, once in a fasted state), and test-high tablet fasting (single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state).
Period Title: Period 1
STARTED	6	6	6	6	5	6
Received at Least 1 Dose of Study Drug	6	6	6	6	5	6
COMPLETED	6	6	4	6	5	6
NOT COMPLETED	0	0	2	0	0	0
Period Title: Period 1
STARTED	6	6	4	6	5	6
COMPLETED	6	6	4	6	5	6
NOT COMPLETED	0	0	0	0	0	0
Period Title: Period 1
STARTED	6	6	4	6	5	6
COMPLETED	6	6	4	5	5	6
NOT COMPLETED	0	0	0	1	0	0
Period Title: Period 1
STARTED	6	6	4	5	5	6
COMPLETED	6	5	4	4	5	6
NOT COMPLETED	0	1	0	1	0	0
Period Title: Period 1
STARTED	6	5	4	4	5	6
COMPLETED	6	5	4	4	5	6
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	LY2409021 Cohort 1	LY2409021 Cohort 2	Total
Arm/Group Description	Participants randomized to 1 of 3 sequences and received a single but different intervention per period: Sequence 1 (reference capsules fasting, then test-medium tablet fasting, then test-medium tablet after high-fat meal), Sequence 2 (test-medium tablet fasting, then test-medium tablet after high-fat meal, then reference capsules fasting), or Sequence 3 (test-medium tablet after high-fat meal, then reference capsules fasting, then test-medium tablet fasting). There was a washout period of at least 14 days between interventions. Description of interventions: reference capsules fasting [20-milligram (mg) LY2409021 dose, administered orally, once in fasted state], test-medium tablet fasting (20-mg LY2409021 tablet, medium particle size, administered orally, once in fasted state), and test-medium tablet after high-fat meal (20-mg LY2409021 tablet, medium particle size, administered orally, once, immediately after standardized high-fat meal).	Participants randomized to 1 of 3 sequences and received a single but different intervention per period: Sequence 4 (test-medium tablet fasting then, test-high tablet fasting, then test-low tablet fasting), Sequence 5 (test-high tablet fasting then, test-low tablet fasting, then test-medium tablet fasting), or Sequence 6 (test-low tablet fasting, then test-medium tablet fasting, then test-high tablet fasting). There was a washout period of at least 14 days between interventions. Description of interventions: test-low tablet fasting (single 20-mg LY2409021 tablet of a low particle size, administered orally in a fasted state), test-medium tablet fasting (single 20-mg LY2409021 tablet of a medium particle size, administered orally, once in a fasted state), and test-high tablet fasting (single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state).	Total of all reporting groups
Overall Participants	18	17	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.4 (10.7)	32.6 (9.7)	33.6 (10.1)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 11.8%	2 5.7%
Male	18 100%	15 88.2%	33 94.3%
Race/Ethnicity, Customized (Count of Participants)
Asian	18 100%	17 100%	35 100%
Region of Enrollment (Count of Participants)
Singapore	18 100%	17 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Medium Test Form to Reference Form
Description	AUC from time 0 to infinity (AUC0-∞).
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohort 1 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 1 (Test-Medium Tablet Fasted)	LY2409021 Cohort 1 (Reference Capsules Fasted)
Arm/Group Description	A single 20-milligram (mg) LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A 20-mg LY2409021 dose administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	16	15
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per milliliter (ng*hr/mL)]	65300 (20)	62800 (38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Test-Medium Tablet Fasted), LY2409021 Cohort 1 (Reference Capsules Fasted)
	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	1.03
	Confidence Interval	(2-Sided) 90%; 0.897 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC0-∞ was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

2. Primary Outcome

Title	Pharmacokinetics, Maximum Concentration (Cmax): Medium Test Form to Reference Form
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohort 1 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 1 (Test-Medium Tablet Fasted)	LY2409021 Cohort 1 (Reference Capsules Fasted)
Arm/Group Description	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A 20-mg LY2409021 dose administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	16	15
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	779 (19)	726 (41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Test-Medium Tablet Fasted), LY2409021 Cohort 1 (Reference Capsules Fasted)
	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	1.06
	Confidence Interval	(2-Sided) 90%; 0.922 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

3. Secondary Outcome

Title	Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Standardized High Fat Meal to Fasting
Description	AUC from time 0 to infinity (AUC0-∞).
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohort 1 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 1 (Test-Medium Tablet Fed)	LY2409021 Cohort 1 (Test-Medium Tablet Fasted)
Arm/Group Description	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once, immediately after a standardized high-fat meal, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	18	16
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*hr/mL)]	67000 (18)	65300 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Test-Medium Tablet Fasted), LY2409021 Cohort 1 (Reference Capsules Fasted)
	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	1.02
	Confidence Interval	(2-Sided) 90%; 0.896 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC0-∞ was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

4. Secondary Outcome

Title	Pharmacokinetics, Maximum Concentration (Cmax): Standardized High Fat Meal to Fasting
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohort 1 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 1 (Test-Medium Tablet Fed)	LY2409021 Cohort 1 (Test-Medium Tablet Fasted)
Arm/Group Description	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once, immediately after a standardized high-fat meal, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	18	16
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	785 (14)	779 (19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Test-Medium Tablet Fasted), LY2409021 Cohort 1 (Reference Capsules Fasted)
	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	1.01
	Confidence Interval	(2-Sided) 90%; 0.882 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

5. Secondary Outcome

Title	Pharmacokinetics, Time to Maximum Concentration (Tmax)
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohorts 1 and 2 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 1 (Reference Capsules Fasted)	LY2409021 Cohort 1 (Test-Medium Tablet Fed)	LY2409021 Cohort 1 (Test-Medium Tablet Fasted)	LY2409021 Cohort 2 (Test-Low Tablet Fasted)	LY2409021 Cohort 2 (Test-Medium Tablet Fasted)	LY2409021 Cohort 2 (Test-High Tablet Fasted)
Arm/Group Description	A 20-mg LY2409021 dose administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once, immediately after a standardized high-fat meal, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a low particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	15	18	16	15	17	17
Median (Full Range) [hour (hr)]	8.00	8.00	8.00	4.00	8.00	8.00

6. Secondary Outcome

Title	Pharmacokinetics, Area Under the Concentration-Time Curve (AUC): Low and High Particle Size to Medium Particle Size
Description	AUC from time 0 to infinity (AUC0-∞).
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohort 2 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 2 (Test-Low Tablet Fasted)	LY2409021 Cohort 2 (Test-High Tablet Fasted)	LY2409021 Cohort 2 (Test-Medium Tablet Fasted)
Arm/Group Description	A single 20-mg LY2409021 tablet of a low particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	15	17	17
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per milliliter (ng*hr/mL)]	73700 (16)	69400 (18)	73600 (17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Test-Medium Tablet Fasted), LY2409021 Cohort 1 (Test-Medium Tablet Fasted)
	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	0.993
	Confidence Interval	(2-Sided) 90%; 0.951 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC0-∞ was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Reference Capsules Fasted), LY2409021 Cohort 1 (Test-Medium Tablet Fasted)
	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	0.943
	Confidence Interval	(2-Sided) 90%; 0.905 to 0.983
	Parameter Dispersion	Type: Value:
	Estimation Comments	AUC0-∞ was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

7. Secondary Outcome

Title	Pharmacokinetics, Concentration Maximum (Cmax): Low and High Particle Size to Medium Particle Size
Time Frame	Periods 1, 2, 3 (predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96, 144, 192, 240, 288, and 336 hours postdose)

Outcome Measure Data

Analysis Population Description

Randomized participants in Cohort 2 who received the specified study drug.

Arm/Group Title	LY2409021 Cohort 2 (Test-Low Tablet Fasted)	LY2409021 Cohort 2 (Test-High Tablet Fasted)	LY2409021 Cohort 2 (Test-Medium Tablet Fasted)
Arm/Group Description	A single 20-mg LY2409021 tablet of a low particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state, during Period 1, 2, or 3.	A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.
Measure Participants	15	17	17
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	835 (20)	793 (20)	844 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Test-Medium Tablet Fasted), LY2409021 Cohort 1 (Test-Medium Tablet Fasted)
	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	0.980
	Confidence Interval	(2-Sided) 90%; 0.926 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2409021 Cohort 1 (Reference Capsules Fasted), LY2409021 Cohort 1 (Test-Medium Tablet Fasted)
	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	0.940
	Confidence Interval	(2-Sided) 90%; 0.891 to 0.993
	Parameter Dispersion	Type: Value:
	Estimation Comments	Cmax was log-transformed and analyzed using a linear mixed effects model with fixed factors for formulation, sequence, and period, and random factor for participant.

Adverse Events

Arm/Group Title	LY2409021 Cohort 1 (Reference Capsules Fasted)		LY2409021 Cohort 1 (Test-Medium Tablet Fed)		LY2409021 Cohort 2 (Test-Low Tablet Fasted)		LY2409021 Cohorts 1 and 2 (Test-Medium Tablet Fasted)		LY2409021 Cohort 2 (Test-High Tablet Fasted)
Arm/Group Description	A 20-mg LY2409021 dose administered orally, once in a fasted state, during Period 1, 2, or 3.		A single 20-mg LY2409021 tablet of a medium particle size administered orally, once, immediately after a standardized high-fat meal, during Period 1, 2, or 3.		A single 20-mg LY2409021 tablet of a low particle size administered orally, once in a fasted state, during Period 1, 2, or 3.		A single 20-mg LY2409021 tablet of a medium particle size administered orally, once in a fasted state, during Period 1, 2, or 3.		A single 20-mg LY2409021 tablet of a high particle size administered orally, once in a fasted state, during Period 1, 2, or 3.
All Cause Mortality
	LY2409021 Cohort 1 (Reference Capsules Fasted)		LY2409021 Cohort 1 (Test-Medium Tablet Fed)		LY2409021 Cohort 2 (Test-Low Tablet Fasted)		LY2409021 Cohorts 1 and 2 (Test-Medium Tablet Fasted)		LY2409021 Cohort 2 (Test-High Tablet Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2409021 Cohort 1 (Reference Capsules Fasted)		LY2409021 Cohort 1 (Test-Medium Tablet Fed)		LY2409021 Cohort 2 (Test-Low Tablet Fasted)		LY2409021 Cohorts 1 and 2 (Test-Medium Tablet Fasted)		LY2409021 Cohort 2 (Test-High Tablet Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/18 (0%)		0/15 (0%)		0/33 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	LY2409021 Cohort 1 (Reference Capsules Fasted)		LY2409021 Cohort 1 (Test-Medium Tablet Fed)		LY2409021 Cohort 2 (Test-Low Tablet Fasted)		LY2409021 Cohorts 1 and 2 (Test-Medium Tablet Fasted)		LY2409021 Cohort 2 (Test-High Tablet Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/15 (80%)		17/18 (94.4%)		7/15 (46.7%)		22/33 (66.7%)		9/17 (52.9%)
Cardiac disorders
Palpitations	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	0/33 (0%)	0	1/17 (5.9%)	1
Gastrointestinal disorders
Diarrhoea	0/15 (0%)	0	0/18 (0%)	0	2/15 (13.3%)	2	1/33 (3%)	1	1/17 (5.9%)	1
Mouth ulceration	0/15 (0%)	0	1/18 (5.6%)	1	0/15 (0%)	0	0/33 (0%)	0	0/17 (0%)	0
Vomiting	0/15 (0%)	0	0/18 (0%)	0	1/15 (6.7%)	1	0/33 (0%)	0	0/17 (0%)	0
General disorders
Hunger	1/15 (6.7%)	1	1/18 (5.6%)	2	3/15 (20%)	3	1/33 (3%)	1	2/17 (11.8%)	2
Vessel puncture site haematoma	4/15 (26.7%)	5	6/18 (33.3%)	10	2/15 (13.3%)	2	9/33 (27.3%)	12	3/17 (17.6%)	4
Vessel puncture site pain	2/15 (13.3%)	3	1/18 (5.6%)	1	0/15 (0%)	0	2/33 (6.1%)	3	2/17 (11.8%)	2
Vessel puncture site reaction	1/15 (6.7%)	1	2/18 (11.1%)	2	0/15 (0%)	0	1/33 (3%)	1	1/17 (5.9%)	1
Vessel puncture site swelling	3/15 (20%)	3	2/18 (11.1%)	2	0/15 (0%)	0	1/33 (3%)	1	0/17 (0%)	0
Infections and infestations
Hordeolum	0/15 (0%)	0	0/18 (0%)	0	1/15 (6.7%)	1	0/33 (0%)	0	0/17 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/15 (0%)	0	0/18 (0%)	0	1/15 (6.7%)	1	0/33 (0%)	0	0/17 (0%)	0
Excoriation	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	2/33 (6.1%)	2	1/17 (5.9%)	1
Procedural site reaction	6/15 (40%)	8	9/18 (50%)	13	3/15 (20%)	3	10/33 (30.3%)	15	1/17 (5.9%)	1
Scratch	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	0/33 (0%)	0	1/17 (5.9%)	1
Investigations
Coagulation time prolonged	1/15 (6.7%)	1	0/18 (0%)	0	0/15 (0%)	0	0/33 (0%)	0	0/17 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/15 (6.7%)	1	0/18 (0%)	0	0/15 (0%)	0	0/33 (0%)	0	1/17 (5.9%)	1
Hypoglycaemia	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	2/33 (6.1%)	2	0/17 (0%)	0
Musculoskeletal and connective tissue disorders
Neck pain	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	0/33 (0%)	0	1/17 (5.9%)	1
Nervous system disorders
Dizziness	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	2/33 (6.1%)	2	0/17 (0%)	0
Headache	2/15 (13.3%)	2	0/18 (0%)	0	0/15 (0%)	0	5/33 (15.2%)	5	0/17 (0%)	0
Lethargy	0/15 (0%)	0	1/18 (5.6%)	1	0/15 (0%)	0	0/33 (0%)	0	0/17 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/15 (0%)	0	1/18 (5.6%)	1	0/15 (0%)	0	1/33 (3%)	1	0/17 (0%)	0
Dry throat	0/15 (0%)	0	0/18 (0%)	0	1/15 (6.7%)	1	0/33 (0%)	0	1/17 (5.9%)	1
Oropharyngeal pain	1/15 (6.7%)	1	2/18 (11.1%)	2	0/15 (0%)	0	3/33 (9.1%)	3	0/17 (0%)	0
Productive cough	0/15 (0%)	0	2/18 (11.1%)	2	0/15 (0%)	0	0/33 (0%)	0	1/17 (5.9%)	1
Rhinorrhoea	2/15 (13.3%)	2	1/18 (5.6%)	1	1/15 (6.7%)	1	2/33 (6.1%)	2	2/17 (11.8%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/15 (6.7%)	1	0/18 (0%)	0	0/15 (0%)	0	0/33 (0%)	0	0/17 (0%)	0
Rash	0/15 (0%)	0	0/18 (0%)	0	0/15 (0%)	0	2/33 (6.1%)	2	0/17 (0%)	0
Urticaria	0/15 (0%)	0	1/18 (5.6%)	1	0/15 (0%)	0	0/33 (0%)	0	0/17 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.