The Effects of LY2409021 on the Liver

Study Overview
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Brief Summary
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This is a study that involves multiple doses of study drug (60 mg of LY2409021, 15 mg of LY2409021 or placebo) taken as capsules by mouth on a daily basis for 28 days. This study will image the liver using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in healthy participants and in participants with type 2 diabetes mellitus, when they take LY2409021 to see if liver changes happen at the same time as changes in blood tests. This study is approximately 11 weeks long, not including screening. A screening appointment is required within 28 days prior to the start of the study.

Official Title
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Effects of LY2409021 on Hepatic Metabolism in Healthy Volunteers and Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: LY2409021


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all participants: Must be a male, or a female who cannot become pregnant, and who is either a healthy participant, or who has type 2 diabetes Must have a body mass index (BMI) of 18.5 to 29.9 kilograms per square meter (kg/m^2) if a healthy participant, or a BMI of 18.5 to 35.0 kg/m^2 if diabetic For participants with type 2 diabetes mellitus (T2DM): - On diet and exercise treatment, or taking metformin Exclusion Criteria: For all participants: Have signs or symptoms of liver disease Are infected with hepatitis B or hepatitis C Have donated more than 450 mL of blood in the last 3 months or if have donated any blood in the last month Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic Have had surgery with metallic clips, staples or stents, or have had a cardiac pacemaker (or other surgical implants) inserted in any part of the body, or have fear of enclosed spaces or have symptoms that prevent them from being sent for an magnetic resonance imaging (MRI) scan For participants with T2DM: - Are using insulin

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Part A and B - Up to 4 capsules of placebo administered orally once a day for 28 days. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: 15 mg LY2409021<br>Part B - 1 capsule of 15 mg LY2409021 orally once a day for 28 days. (Arm added in September, 2012, per protocol amendment.) | Drug: LY2409021<br>* Administered orally<br>|
| Experimental: 60 mg LY2409021<br>Part A - 4 capsules of 15 mg LY2409021 administered orally once a day for 28 days. | Drug: LY2409021<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Day 28 in Liver Fat Average Percent (%) | Measured by magnetic resonance (MR) scanning. | Baseline, Day 28 (Pre-meal) | 
| Change From Baseline to Day 28 in Hepatic Glycogen Content | Measured by MR scanning. | Baseline, Day 28 (Pre-meal) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Day 28 in Transaminase Levels |  | Baseline, Day 28 | 
| Change From Baseline to Day 29 in Glucose Response to an Arginine Stimulation Test (AST) (Part A) | Acute glucose response to an AST at a blood glucose level of approximately 250 milligrams per deciliter (mg/dL). | Baseline, Day 29 | 
| Change From Baseline to Day 29 in Glucagon Response to an Arginine Stimulation Test (AST) (Part A) | Acute glucagon response to an AST at a blood glucose level of approximately 250 mg/dL. | Baseline, Day 29 | 
| Change From Baseline to Day 29 in Insulin Response to an Arginine Stimulation Test (AST) (Part A) | Acute insulin response to an AST at a blood glucose level of approximately 250 mg/dL. | Baseline, Day 29 |