A Study of LY2189102 in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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Study to evaluate the safety, tolerability and efficacy of LY2189102 in patients with type 2 diabetes.

Official Title
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Phase 2 Randomized, Double-blind, Placebo Controlled, Parallel Design Study in Patients With Type 2 Diabetes Mellitus Who Are Stable on Diet and Exercise, With or Without Metformin Monotherapy.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: LY2189102
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Type 2 Diabetes and confirmed by fasting C-peptide levels greater than or equal to 0.8 nanograms per milliliter [ng/ml]), with duration of more than 3 months. Body mass index between 25 and 40 kilograms per square meter (kg/m2). Stable on diet and exercise alone, with or without metformin monotherapy (stable regimen or dose for at least 8 weeks). Drug-naïve or previous anti-diabetic pharmacotherapy use is allowed (for the latter, patient must have stopped taking pharmacotherapy greater than 12 weeks prior to screening and only if deemed appropriate by the investigator). Angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, thiazide diuretics or calcium channel blockers are permitted for the treatment of hypertension or proteinuria. Glycated hemoglobin level between 7% and 10%. Baseline High-sensitivity C-reactive protein greater than or equal to 2 milligrams per liter (mg/L) Females of childbearing potential (not surgically sterilized and between menarche and 1 year post-menopause) must test negative for pregnancy at the time of enrollment based on a pregnancy test. Furthermore, sexually active female and male participants must agree to use 2 reliable methods of birth control during the study and for 3 months following the last dose of study drug. Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. Exclusion Criteria: Current use of anti-diabetic pharmacotherapy (except metformin, under conditions specified in Inclusion Criteria above). Current treatment with anti-inflammatory drugs, including corticosteroids and non-steroidal anti-inflammatory drugs (100 mg per day or less of aspirin allowed). Within 60 days of the initial dose of the study drug, have received treatment with a drug that has not received regulatory approval for any indication. Presence of autoantibodies to glutamic acid decarboxylase 65 or islet-cell autoantibody-2. Evidence of tuberculosis as documented by a specific assay, medical history, and chest x-ray. A specific assay, (for example, tuberculin testing) will be conducted unless it is medically inappropriate. Exceptions include patients with a history of a positive specific assay for TB who have been treated with isonicotinyl hydrazine (documented) for at least 6 months, or patients with a previous diagnosis of TB who have been appropriately treated and can provide documentation. Symptomatic herpes zoster within 3 months of randomization. Show evidence of hepatitis C and/or positive hepatitis B surface antigen. Show evidence of human immunodeficiency virus and/or positive test of antibodies to human immunodeficiency virus (HIV). Received live or attenuated vaccine(s) within the previous 3 months prior to randomization or will receive within 3 months from the end of study. Screening serum creatinine greater than 2.0 milligrams per deciliter (mg/dL). Serum aspartate aminotransferase or alanine aminotransaminase concentration greater than 2x the upper limit of normal. Known allergies to LY2189102 or excipients. Previously completed or withdrawn from this study or any other study investigating LY2189102. Have donated blood of greater than 500 mL within the preceding 30 days and intend to donate within 3 months from the end of study. Have had other recent or ongoing signs of infection (for example, fever, current treatment with antibiotics). Experienced a serious bacterial infection within 6 months of randomization. Have a serious medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine, or neurological disease, or any clinically significant laboratory abnormality. Have had lymphoma, leukemia, or any non-breast malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease. Have had a previous reaction to other biologics that, in the opinion of the investigator, puts the patient at serious risk.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.6 milligrams (mg) LY2189102<br> | Drug: LY2189102<br>* Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.<br>|
| Experimental: 18 mg LY2189102<br> | Drug: LY2189102<br>* Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.<br>|
| Experimental: 180 mg LY2189102<br> | Drug: LY2189102<br>* Participants received 2 subcutaneous (SC) injections weekly for 12 weeks.<br>|
| Placebo Comparator: Placebo<br>0.9% Sodium Chloride | Drug: Placebo<br>* Participants received 2 SC injections weekly for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at 12 Weeks | Change in HbA1c from baseline following 12 weeks of therapy (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline HbA1c as a continuous covariate. | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Glucose at 12 Weeks | Change in fasting glucose following 12 weeks of therapy (that is, fasting glucose at week 12 minus fasting glucose at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate. | Baseline, 12 weeks | 
| Change From Baseline in Insulin Sensitivity (Fasting Insulin) at 12 Weeks | Change in serum fasting insulin from baseline to endpoint (that is, serum insulin at week 12 minus serum insulin at week 0). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate. | Baseline, 12 weeks | 
| Number of Participants With a Change From Baseline in Beta-Cell Function Measured by Glucose and Insulin Changes With the Mixed Meal Tolerance Test (MMTT) at 12 Weeks | The number of participants with a change from baseline in glucose and insulin at 2 hours after the MMTT was analyzed. The MMTT measures glucose and insulin before and after a standardized meal is eaten. Glucose and insulin levels were measured before the MMTT and 2 hours after the MMTT. | Baseline, 12 weeks | 
| Change From Baseline in the Glycosylated Hemoglobin (HbA1c) at Week 10 and Week 12 | The change from baseline in HbA1c at week 10 (that is HbA1c at week 10 minus HbA1c at baseline) and week 12 (that is, HbA1c at week 12 minus HbA1c at baseline). The Least Squares (LS) Mean Value was based on an analysis of covariance (ANCOVA) model with treatment and site as class variables and baseline value as a continuous covariate. | Baseline, week 10, week 12 | 
| Pharmacokinetics (PK) Maximum Serum Concentration (Cmax) of LY2189102 at End of Dosing (12 Weeks) | The Cmax value measures the maximum serum concentration and is estimated for LY2189102. The values were generated as individual estimates from a population pharmacokinetics (PK) model. Placebo samples were not assayed for serum concentration of LY2189102 because the participants in the placebo treatment arm did not receive LY2189102 study drug. | Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose | 
| PK: Area Under the Concentration Time Curve for Dosing Interval (Tau) at Steady State (AUCτ,SS) at End of Dosing (12 Weeks) | Individual estimates of AUCtau at end of dosing generated from a population pharmacokinetic (PK) model. | Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose | 
| Pharmacokinetics Measured by Serum Concentration at End of Dosing (12 Weeks) | Pharmacokinetics Measured by Serum Concentration at End of Dosing. | Prior to and 1 and 3-4 days after the first dose, prior to every other dose, and 6 and 12 weeks after the last dose | 

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