A Study of Multiple Increasing Doses of LY2409021 in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The study drug LY2409021 is being evaluated as a possible treatment for diabetes. The primary purpose of this study is to help answer the following research questions, and not to provide treatment for diabetes : The safety of LY2409021 and any side effects that might be associated with it following 4 weeks of doses How long it takes the body to absorb and remove LY2409021 following dosing over 4 weeks How daily dosing of LY2409021 affects blood levels of sugar (glucose), insulin and other naturally occurring substances before and after a meal How LY2409021 works when given with metformin How daily dosing of LY2409021 affects the cells that produce insulin

Official Title
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The Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Multiple Escalating Doses of LY2409021 in 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: Must be either a male, or a female who cannot become pregnant, who has type 2 diabetes and is either controlling diabetes through diet and exercise, or taking metformin Have an hemoglobin A1c (HbA1c) value at screening of greater than or equal to 6.5% and less than or equal to 10.0% on a stable treatment regimen at the time of measurement Have a screening body mass index (BMI) of 20 to 40 kg/m^2 inclusive Have a blood pressure reading at screening of between 90 to 160 millimeters of mercury (mmHg) (systolic) and 40 to 95 mmHg (diastolic) Exclusion Criteria: Have used insulin for diabetic control within 1 year of study entry Have used thiazolidinediones within 3 months, or any other drugs for treatment of hyperglycemia (except metformin) within 1 month, prior to first planned dosing. Metformin is acceptable for this study. Have clinically significant coronary artery disease Have clinically significant peripheral vascular disease Have clinical evidence of active diabetic proliferative retinopathy Have known significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis Impaired renal function (serum creatinine greater than 115 micromoles/liter [μmol/L] [1.3 mg/dL] in women, greater than 130 μmol/L [1.5 mg/dL] in men) Have triglycerides greater than 4.5 millimoles per liter (mmol/L) [approximately 400 mg/dL] at screening Were hospitalized for poor control of diabetes (keto-acidotic episode) in the last 6 months Are allergic to LY2409021 or similar drugs Have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (other than diabetes), hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data Have used systemic glucocorticoids within 1 month prior to first dosing Have donated 450 mL or more of blood in the last 3 months or have donated any blood within the last month Have a regular alcohol intake greater than 21 units/week (male), or 14 units/week (female), or are unwilling to stop alcohol as required by the study restrictions (1 unit = 360 mL of beer, or 150 mL of wine, or 45 mL of spirits)

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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No

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo administered orally once daily for 4 weeks | Drug: Placebo<br>* Administered orally (capsule)<br>|
| Experimental: 5 mg LY2409021<br>5 mg LY2409021 administered orally once daily for 4 weeks | Drug: LY2409021<br>* Administered orally (capsule)<br>|
| Experimental: 30 mg LY2409021<br>30 mg LY2409021 administered orally once daily for 4 weeks | Drug: LY2409021<br>* Administered orally (capsule)<br>|
| Experimental: 60 mg LY2409021<br>60 mg LY2409021 administered orally once daily for 4 weeks | Drug: LY2409021<br>* Administered orally (capsule)<br>|
| Experimental: 90 mg LY2409021<br>90 mg LY2409021 administered orally once daily for 4 weeks | Drug: LY2409021<br>* Administered orally (capsule)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with one or more drug related adverse events (AEs) or any serious AEs |  | From first dose of study drug up to discharge (at least 28 days after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area under the concentration curve (AUC) of LY2409021 |  | From first study drug dose to Day 28 post last dose | 
| Pharmacokinetics: Maximum concentration (Cmax) of LY2409021 |  | From first study drug dose to Day 28 post last dose | 
| Change in fasting blood glucose level |  | From Day -1 to Day 28 of dosing | 
| Change in incremental area under the curve (AUC) for glucose |  | From Day -1 to Day 28 of dosing | 
| Change in homeostasis model assessment of beta cell function (HOMA-B) |  | From baseline to Day 28 | 
| Change in fasting glucagon level |  | From Day -1 to Day 28 of dosing | 
| Change in fasting insulin level |  | From Day -1 to Day 28 of dosing | 
| Change in fasting C-peptide level |  | From Day -1 to Day 28 of dosing | 
| Change in fasting glucagon-like peptide-1 (GLP-1) level |  | From Day -1 to Day 28 of dosing |