A Study in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The study is designed to see if once daily oral dosing of LY2608204 will help control diabetes as measured by the glycosylated fraction of hemoglobin A (HbA1c) level. It will also help to determine the safety of the medication and the most useful doses of the medication.

Official Title
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A 12-Week, Phase 2, Randomized, Double-Blind, Active-Controlled Study of LY2608204 Given as Monotherapy or in Combination With Metformin in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LY2608204
* Drug: Glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 2 diabetes mellitus prior to entering the trial May be treated with: Diet and exercise alone or Diet and exercise in combination with a stable dose of metformin for at least 3 months before Screening or Diet and exercise in combination with a stable dose of sulfonylurea or meglitinide (repaglinide, nateglinide) for at least 3 months before Screening or Diet and exercise in combination with stable doses of metformin and sulfonylurea or metformin and meglitinides for at least 3 months before Screening and have had diabetes for at least 6 years Must have an Hemoglobin A1c value between 7% and 10% Must have a body mass index (BMI) between 20 and 40 kg/m2 Must have stable weight during the 3 months prior to Screening (weight change not to exceed 5 kg (11 lb)) If female, you must not be able to get pregnant Must be well motivated, capable, and willing to complete study required glucose monitoring and instruction Exclusion Criteria: Use of insulin or any antidiabetic agent other than metformin or sulfonylurea or meglitinide during the 3 months prior to Screening Have a gastrointestinal disease that significantly impacts gastric emptying or motility or have undergone gastric bypass or gastric banding surgery Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness or have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months Are currently taking or have taken within the last 2 months, prescription or over-the counter medications which affect body weight Have cardiac disease with functional status that is New York Heart Association [NYHA] Class II, III, or IV or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure in the past 6 months. Have poorly controlled hypertension, history of malignant hypertension, evidence of renal artery stenosis and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days before randomization Have a QTcB (Bazett's-corrected QT interval) interval greater than 450 msec for men or greater than 470 for women at Screening or any personal history of ventricular tachycardia or unexplained syncope Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or significantly elevated liver blood tests Are currently receiving renal dialysis, have a serum creatinine greater than 2.0 mg/dL (177 μmol/L) or a calculated creatinine clearance of less than 60 ml/min or in patients being treated with metformin, have other known contradictions to metformin use including, but not limited to, a serum creatinine above (or creatinine clearance below) what is approved in the metformin product label Have fasting state hypertriglyceridemia (defined as greater than 5.65 mmol/L, 500 mg/dl) at Screening. If taking lipid-lowering agents, doses of these medications must be stable for 30 days prior to randomization. Are receiving chronic (for more than 2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within 4 weeks immediately prior to Randomization Have an active or untreated malignancy or have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years Have a history of seizure disorder Are currently using or intend to use inhibitors of Cytochrome P450 family 3A (CYP3A4) Currently taking a medication that is a sensitive substrate of the CYP3A4 pathway with a narrow therapeutic index

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2608204<br>80 to 400 mg, Doses will be titrated to reach glycemic targets during the first 4 weeks. The starting dose level depends on the participant's HbA1c level measured at Screening. Administered orally, daily for 12 weeks | Drug: LY2608204<br>* Administered orally<br>|
| Active Comparator: Glimepiride<br>1 to 6 mg, Doses will be titrated to reach glycemic targets during the first 4 weeks. Administered orally, daily for 12 weeks | Drug: Glimepiride<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 12 week endpoint in glycosylated fraction of hemoglobin A (HbA1c) |  | Baseline, 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 12 week endpoint in fasting blood glucose |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint in average Seven Point Self Monitored Blood Glucose |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint for Oral Glucose Tolerance Test (OGTT) |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint in Homa-B: Insulin |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint in Homa-IR: Insulin |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint in Homa-S: Insulin |  | Baseline, 12 weeks | 
| Change from baseline to 12 week endpoint in fasting lipids |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint in free fatty acids |  | Baseline, 12 Weeks | 
| Change from baseline to 12 week endpoint in body weight |  | Baseline, 12 Weeks | 
| Incidence of Hypoglycemic Episodes |  | Baseline through 12 weeks | 
| Percentage of participants at each dose level up to 12 weeks |  | Baseline up to 12 weeks | 
| Pharmacokinetics: Maximum plasma concentration (Cmax) of LY2608204 |  | pre-dose, up to 12 hours post-dose | 
| Number of participants with severe hypoglycemic episodes |  | Baseline through 12 weeks | 
| Rate of hypoglycemic episodes |  | Baseline through 12 weeks | 
| Pharmacokinetics: Area under the curve of concentration-time curve for one dosing interval at steady state (AUC0-tau, ss) of LY2608204 |  | pre-dose, up to 12 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, glimepiride, diabetes type II, diabetes type 2, Type 2 diabetes, diabetes mellitus