A Study for Participants With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This drug is being evaluated for possible treatment of type 2 diabetes mellitus. Participation in this study is expected to last up to 18 weeks. A goal of this study is to determine the safety and effectiveness of LY2409021.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study 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: LY2409021
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion: Participants must either be male or a female who cannot become pregnant, who has type 2 diabetes and is either controlling your diabetes through diet and exercise alone, or with diet and exercise taking metformin. If participants are male, participants are willing to talk to the study doctor about birth control options during the study and for 3 months after the last dose of study medication. Participants must have an Hemoglobin A1c (HbA1c) test of 6.5% to 10% Participants must have a body mass index (BMI) between 25 to 40 kilograms/square meter (kg/m²). Participants must be willing and able to test your blood sugar levels at home with a blood sugar meter. Participants must complete a study diary as instructed by your study doctor and staff and return the study diary as instructed by the study doctor. Participants must maintain consistent dietary, physical activity, and sleeping patterns throughout the study. Exclusion Criteria: Insulin, exenatide, or any diabetic medication other than metformin 3 months prior to screening to control you diabetes, Medications to increase movement in your digestive tract or that slow movement in your digestive tract Over-the-counter drugs or drugs prescribed by your doctor that cause weight loss or high or low blood sugar, Chronically use oral glucocorticoids therapy or have received this type of medication within 8 weeks prior to beginning this study, Class II and III antiarrhythmic agents (commonly used to prevent or relieve an irregular heartbeat), Drugs that damage the liver Fibrates and niacin (both commonly used to treat high cholesterol) more than 1 gram/day (gm/day), Central nervous stimulants, alcohol intake for males that is more than 2 units per day and for females that is more than 1 unit per day [1 unit=12 ounces (oz) or 360 milliliter (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits]. You have had one (1) or more cases of uncontrolled diabetes (very high blood sugars) which required hospitalization in the 6 months prior to the screening visit or have a diagnosis of hypoglycemia (low blood sugar) unawareness. You had two (2) or more emergency room visits or were hospitalized for poor control of your diabetes (for example, keto-acidotic episode) in the last 6 months. Participants have a problem with your stomach such that it empties slowly (diabetic gastroparesis) or you have had gastric bypass (bariatric) surgery. Participants have a personal or family history of pancreatic neoplasia. Participants have abnormal lipids (for example triglycerides). Participants have had problems with your heart in the past 6 months, such as a heart attack, chest pain (angina), heart failure, heart bypass operation, angioplasty (a medical procedure to open a narrow or clogged blood vessel of the heart) or stent insertion (a procedure to insert a wire mesh tube to prop open a blood vessel after angioplasty), a heart rhythm problem, or a stroke. Participants have an elevated or uncontrolled blood pressure. Participant's electrocardiogram (ECG, a test that measures the electrical activity of your heart) is outside the normal limits, as determined by the study doctor. Participants have a problem with your kidneys or are on dialysis. Participants have a problem with your pancreas. Participants must not have nor had liver disease (for example, Hepatitis B or C). Participants have cancer, except for skin cancer or have been in remission (the absence of disease activity) from cancer for less than 5 years. Participants have a serious or uncontrolled health problems (other than type 2 diabetes), blood disorders or laboratory tests that in the opinion of the doctor, could interfere with understanding the results of this study. The doctor will let you know if this applies to you. Participants previously completed or withdrew from this study or any other study investigating LY2409021. Participants are allergic to the study drug or other related drugs. You cannot be in this study if you are a woman and you possibly could become pregnant during this study.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 4 capsules by mouth once daily for 12 weeks<br>|
| Experimental: LY2409021 10 milligrams (mg)<br> | Drug: LY2409021<br>* 4 capsules by mouth taken once daily for 12 weeks<br>|
| Experimental: LY2409021 30 mg<br> | Drug: LY2409021<br>* 4 capsules by mouth taken once daily for 12 weeks<br>|
| Experimental: LY2409021 60 mg<br> | Drug: LY2409021<br>* 4 capsules by mouth taken once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Glycosylated Hemoglobin A1c (HbA1c) | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was calculated using a mixed-model repeated measures analysis (MMRM) that included terms for treatment group, baseline HbA1c, metformin use, visit, and visit-by-treatment interaction. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Values for Fasting Blood Glucose (FBG) | LS mean was calculated using a MMRM that included terms for treatment group, baseline value, metformin use, visit, and visit-by-treatment interaction. | Baseline, Week 12 | 
| Change From Baseline for Glucose Area Under the Curve (AUC) From Oral Glucose Tolerance Test (OGTT) | LS mean was calculated using analysis of covariance (ANCOVA) model that included terms for treatment group, baseline value and metformin use. | Baseline, Week 12 | 
| Change From Baseline to Endpoint for Fasting Triglycerides | LS mean was calculated using ANCOVA model that included terms for treatment group, baseline value and metformin use. | Baseline, Week 12 | 
| Total and Sub-Domain Scores of Diabetes Symptom Checklist-Revised (DSC-R) | The DSC-R was a participant completed questionnaire that was designed to assess the presence and perceived burden of diabetes-related symptoms. Participants were asked to recall the last 4 weeks and consider each symptom/item in terms of whether they experienced it and if so, how troublesomeness it was. Participants were to consider troublesomeness of the symptom on a 1 (not at all) to 5 (extremely) point scale. There were a total of 34 items, grouped into 8 subscales: cardiovascular (4 items), psychological-cognitive distress (4 items), psychological-fatigue (4 items), hyperglycemic (4 items), hypoglycemic (3 items), neurological-pain (4 items), neurological-sensory (6 items) and visual (5 items). Sub-domain score calculated as: (sum of item scores) divided by (number of items), scores ranged from 1 to 5. Total score was the sum of all sub-domains and ranged from 8 to 40. Higher scores of total and subscales indicated worsened symptoms. | Baseline, Week 12 | 
| Change From Baseline in the Diabetes Medicines Survey Perceived Effectiveness and Physical Side-Effects (Differences Between Perceptions About Medication-Diabetes Scores Between Placebo and LY2409021) | The Diabetes Medicines Survey was a participant reported questionnaire consisting of 25 items: perceived effectiveness of diabetes medicines (items 1-10) and physical side-effects (items 11-25). Both domains had a scores range from 1 (all of the time) to 4 (none of the time) and a possible total scores range from 25 to 100. Lower scores for perceived effectiveness items indicated a better perceived effectiveness. Lower scores for physical side-effects items indicated a greater frequency of physical side-effects. | Baseline, Week 12 | 
| Change From Baseline Values for 7-Point Self-Monitored Blood Glucose (SMBG) Profiles | Participants obtained 7-point SMBG values immediately before and 2 hours after each meal and at bedtime. LS mean was calculated using a MMRM that included terms for treatment group, baseline value, metformin use, visit, and visit-by-treatment interaction. | Baseline, Week 12 | 
| Change From Baseline Values for Fasting Insulin | LS mean was calculated using a MMRM that included terms for treatment group, baseline value, metformin use, visit, and visit-by-treatment interaction. | Baseline, Week 12 | 
| Change From Baseline Values for Fasting Glucagon | LS mean was calculated using a MMRM that included terms for treatment group, baseline value, metformin use, visit, and visit-by-treatment interaction. | Baseline, Week 12 | 
| Change From Baseline Values for Fasting Glucagon-Like Peptide 1 (GLP-1) | LS mean was calculated using a MMRM that included terms for treatment group, baseline value, metformin use, visit, and visit-by-treatment interaction. | Baseline, Week 12 | 
| Change From Baseline for Insulin AUC From OGTT | LS mean was calculated using an ANCOVA that included terms for treatment group, baseline value and metformin use. | Baseline, Week 12 | 
| Change From Baseline for C-Peptide AUC From OGTT | LS mean was calculated using an ANCOVA model that included terms for treatment group, baseline value and metformin use. | Baseline, Week 12 | 
| Change From Baseline to Endpoint for Low Density Lipoprotein (LDL) | Fasting LDL LS mean was calculated using ANCOVA that included terms for baseline and treatment. | Baseline, Week 12 | 
| Change From Baseline to Endpoint for High Density Lipoprotein (HDL) | Fasting HDL LS mean was calculated using ANCOVA that included terms for baseline and treatment. | Baseline, Week 12 | 
| Change From Baseline to Endpoint for Non-HDL Cholesterol | Fasting non-HDL cholesterol LS mean was calculated using ANCOVA that included terms for baseline and treatment. | Baseline, Week 12 | 
| Change From Baseline to Endpoint for Total Cholesterol | Fasting total cholesterol LS mean was calculated using ANCOVA that included terms for baseline and treatment. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2