A Study to Compare Two Forms of LY2608204 in Healthy People

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01313286
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 15.7

Study Details

Study Description

Brief Summary

The purpose of this study is to compare 2 formulations of the study drug (LY2608204) in terms of how much gets into the blood stream and how long it takes the body to get rid of it. Information about any side effects that may occur will also be collected.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY2608204 Reference; Drug: LY2608204 Test	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: The Relative Bioavailability of a Proposed Phase 2 LY2608204 Test Formulation Compared With the Current Phase 1 LY2608204 Reference Formulation After Administration of a Single Oral 80-mg Dose in Healthy Subjects
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2608204 Reference, LY2608204 Test Single oral 80 mg dose of LY2608204 reference formulation in period 1; single oral 80 mg dose of LY2608204 test formulation in period 2. There is a washout period of at least 14 days between dosing periods.	Drug: LY2608204 Reference; Administered orally; Other Names: Glucokinase Activator ; Drug: LY2608204 Test; Administered orally.; Other Names: Glucokinase Activator
Experimental: LY2608204 Test, LY2608204 Reference Single oral 80 mg dose of LY2608204 test formulation in period 1; single oral 80 mg dose of LY2608204 reference formulation in period 2. There is a washout period of at least 14 days between dosing periods.	Drug: LY2608204 Reference; Administered orally; Other Names: Glucokinase Activator ; Drug: LY2608204 Test; Administered orally.; Other Names: Glucokinase Activator

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) [Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours]

   Area under the concentration versus time curve from zero to infinity [AUC(0-∞)] was calculated from the data. The values for AUC were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject.

2. Maximum Observed Drug Concentration (Cmax) [Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours]

   Maximum observed drug concentration (Cmax) was observed from the data. The values for Cmax were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject.

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 a healthy male or a female who cannot become pregnant

• Must have body mass index (BMI) of 18.5 to 32 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

• Must have given written informed consent

Exclusion Criteria:

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

• Have participated in this study or any other study with LY2608204 before

• Have taken drugs similar to LY2608204 (glucokinase activators) before and was found to be allergic to the drug

• Have drug allergy to more than 3 types of medications given by injection

• 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

• Are unwilling to follow dietary restrictions/requirements for the study including (i) refrain from consuming foods or beverages containing grapefruit pomelo, star fruit, or Seville orange within 14 days of the start of the study drug dosing until collection of the last blood sample for drug assay; (ii) consume only the meals provided during dosing day at the clinical research unit (CRU)

• 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 milliliter (mL) or more of blood in the last 3 months (this is about the same as the usual volume given in a blood donation)

• The study doctor thinks the subject 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 personal 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 9AM - 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: NCT01313286
• Other Study ID Numbers: 14233; I3P-FW-GKBG
• First Posted: Mar 11, 2011
• Last Update Posted: Oct 5, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Eli Lilly and Company: Diabetes Mellitus, Type 2
• Additional relevant MeSH terms: Globalagliatin

Study Results

Participant Flow

Arm/Group Title	LY2608204 Reference, LY2608204 Test	LY2608204 Test, LY2608204 Reference
Arm/Group Description	A single oral dose of 80 mg LY2608204 reference formulation in Period 1 and a single oral dose of 80 mg LY2608204 test formulation in Period 2. There is a washout period of at least 14 days between dosing periods.	A single oral dose of 80 mg LY2608204 test formulation in Period 1 and a single oral dose of 80 mg LY2608204 reference formulation in Period 2. There is a washout period of at least 14 days between dosing periods.
Period Title: Period 1
STARTED	8	8
COMPLETED	6	8
NOT COMPLETED	2	0
Period Title: Period 1
STARTED	6	8
COMPLETED	6	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	A single oral dose of 80 mg LY2608204 reference formulation in Period 1 and a single oral dose of 80 mg LY2608204 test formulation in Period 2; or a single oral dose of 80 mg test formulation in Period 1 and a single oral dose of 80 mg reference formulation in Period 2. There is a washout period of at least 14 days between dosing periods.
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.3 (10.1)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	16 100%
Race/Ethnicity, Customized (Count of Participants)
Asian	14 87.5%
White	2 12.5%
Region of Enrollment (Count of Participants)
Singapore	16 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])
Description	Area under the concentration versus time curve from zero to infinity [AUC(0-∞)] was calculated from the data. The values for AUC were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject.
Time Frame	Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours

Outcome Measure Data

Analysis Population Description

All randomized participants who took at least one dose of study drug.

Arm/Group Title	LY2608204 Free Base (Reference Formulation)	LY2608204 Hydrochloride (HCl) Salt (Test Formulation)
Arm/Group Description	a single oral dose of 80 mg LY2608204 reference formulation (free base)	a single oral dose of 80 mg LY2608204 test formulation (HCl salt)
Measure Participants	16	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram.hour per milliliter (ng.h/mL)]	974 (39)	1080 (35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2608204 Free Base (Reference Formulation), LY2608204 Hydrochloride (HCl) Salt (Test Formulation)
	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 Square means
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 90%; 1.00 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Maximum Observed Drug Concentration (Cmax)
Description	Maximum observed drug concentration (Cmax) was observed from the data. The values for Cmax were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject.
Time Frame	Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours

Outcome Measure Data

Analysis Population Description

All randomized participants who took at least one dose of study drug.

Arm/Group Title	LY2608204 Free Base (Reference Formulation)	LY2608204 Hydrochloride (HCl) Salt (Test Formulation)
Arm/Group Description	a single oral dose of 80 mg LY2608204 reference formulation (free base)	a single oral dose of 80 mg LY2608204 test formulation (HCl salt)
Measure Participants	16	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	24.9 (27)	30.3 (33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LY2608204 Free Base (Reference Formulation), LY2608204 Hydrochloride (HCl) Salt (Test Formulation)
	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 Square means
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 90%; 1.07 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	LY2608204 Reference Formulation		LY2608204 Test Formulation
Arm/Group Description	A single oral dose of 80 mg LY2608204 reference formulation.		A single oral dose of 80 mg LY2608204 test formulation.
All Cause Mortality
	LY2608204 Reference Formulation		LY2608204 Test Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2608204 Reference Formulation		LY2608204 Test Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	LY2608204 Reference Formulation		LY2608204 Test Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/16 (62.5%)		10/14 (71.4%)
General disorders
Fatigue	0/16 (0%)	0	1/14 (7.1%)	1
Hunger	4/16 (25%)	5	3/14 (21.4%)	3
Infusion site pain	0/16 (0%)	0	1/14 (7.1%)	1
Vessel puncture site haematoma	4/16 (25%)	5	5/14 (35.7%)	7
Vessel puncture site reaction	7/16 (43.8%)	7	2/14 (14.3%)	2
Vessel puncture site swelling	1/16 (6.3%)	1	1/14 (7.1%)	1
Immune system disorders
Hypersensitivity	0/16 (0%)	0	1/14 (7.1%)	1
Infections and infestations
Herpes zoster	0/16 (0%)	0	1/14 (7.1%)	1
Upper respiratory tract infection	0/16 (0%)	0	2/14 (14.3%)	2
Injury, poisoning and procedural complications
Lower limb fracture	0/16 (0%)	0	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	0/16 (0%)	0	1/14 (7.1%)	1
Nervous system disorders
Dizziness	0/16 (0%)	0	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Erythema	0/16 (0%)	0	1/14 (7.1%)	1

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.