A Comparison of Adding Exenatide With Switching to Exenatide in Patients With Type 2 Diabetes Experiencing Inadequate Glycemic Control With Sitagliptin Plus Metformin

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ceasing sitagliptin and switching to exenatide and metformin is non-inferior to adding exenatide to sitagliptin and metformin, in those patients with type 2 diabetes who are experiencing inadequate glycemic control with a combination of sitagliptin and metformin.

Official Title
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A Comparison of Adding Exenatide With Switching to Exenatide in Patients With Type 2 Diabetes Experiencing Inadequate Glycemic Control With Sitagliptin Plus Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide and sitagliptin
* Drug: exenatide and placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with type 2 diabetes Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 100 mg/day sitagliptin and ≥1500 mg/day metformin, or maximum tolerated dose (extended release or immediate-release). Have inadequate glycemic control as evidenced by an HbA1c between 7.1% and 9%, inclusive. Have a body mass index (BMI) ≥20 kg/m2 and <45 kg/m2 Exclusion Criteria: Are currently enrolled in, or discontinued within the last 30 days (or longer, if local guidelines require) from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Have previously completed or withdrawn from this study or any other study investigating exenatide. Have a known allergy or hypersensitivity to exenatide, sitagliptin or excipients contained in exenatide or sitagliptin. Used drugs for weight loss (for example, orlistat, sibutramine, phenylpropanolamine, or similar over-the-counter medications) within 1 month of screening. Are currently treated with any of the following excluded medications: Thiazolidinediones (TZD) within 3 months of screening. Sulfonylurea (SU) within 3 months of screening. Dipeptidyl peptidase-4 [DPP-4] inhibitors, with the exception of sitagliptin, within 3 months of screening. Meglitinide derivatives (for example, repaglinide or nateglinide) within 3 months of screening. Alpha-glucosidase inhibitors (for example, miglitol or acarbose) within 3 months of screening. Exogenous insulin within the 3 months prior to screening. Drugs that directly affect gastrointestinal motility, including, but not limited to: metoclopramide, cisapride, and chronic macrolide antibiotics. Systemic corticosteroids (excluding topical and inhaled preparations) by oral, intravenous (IV), or intramuscular (IM) route used regularly (for longer than 1 month) or used within 1 month immediately prior to screening. Any other oral antidiabetic (OAD) agent, other than sitagliptin or metformin, within 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: exenatide and sitagliptin<br>* exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; sitagliptin-100mg tablet orally once a day<br>* Other names: exenatide-Byetta; sitagliptin-Januvia;|
| Placebo Comparator: 2<br> | Drug: exenatide and placebo<br>* exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; placebo-tablet orally once a day<br>* Other names: exenatide-Byetta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Percent) | Change in HbA1c from baseline to endpoint (Week 20); difference of base percent values [X% - Y%] | Baseline to 20 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c <=7.0% | Percentage of patients whose baseline HbA1c was > 7.0% achieving HbA1c <=7.0% at endpoint (Week 20) | Baseline to 20 Weeks | 
| Percentage of Patients Achieving HbA1c <7.0% | Percentage of patients whose baseline HbA1c was >=7.0% achieving HbA1c <7.0% at endpoint (Week 20) | Baseline to 20 Weeks | 
| Percentage of Patients Achieving HbA1c <=6.5% | Percentage of patients whose baseline HbA1c was > 6.5% achieving HbA1c <=6.5% at endpoint (Week 20) | Baseline to 20 Weeks | 
| Change in FSG (mmol/L) | Change in fasting serum glucose (FSG) from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Change in Body Weight (kg) | Change in body weight from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Change in Waist Circumference (cm) | Change in waist circumference from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Waist-to-Hip Ratio | Change in waist-to-hip ratio from baseline to endpoint (Week20) | Baseline to 20 Weeks | 
| SMBG (mmol/L) | 7 point Self Monitored Blood Glucose Profiles - daily mean value (Week 20) | Baseline to 20 Weeks | 
| Change in Triglycerides (mmol/L) | Change in triglycerides from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Change in HDL (mmol/L) | Change in high-density lipoprotein (HDL) cholesterol from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Change in LDL (mmol/L) | Change in low-density lipoprotein (LDL) cholesterol from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Change in Total Cholesterol (mmol/L) | Change in total cholesterol from baseline to endpoint (Week 20) | Baseline to 20 Weeks | 
| Incidence of Hypoglycemia (Overall) | Incidence of hypoglycemic episodes experienced overall during the study | Baseline to 20 Weeks | 
| Incidence of Severe Hypoglycemia(Overall) | Incidence of severe hypoglycemia experienced overall during the study | Baseline to 20 Weeks | 
| Incidence of Nocturnal Hypoglycemia (Overall) | Incidence of nocturnal hypoglycemia experienced overall during the study | Baseline to 20 Weeks | 
| Incidence of Confirmed Hypoglycemia(Overall) | Incidence of confirmed hypoglycemia experienced overall during the study | Baseline to 20 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide, Byetta, sitagliptin, Januvia, Amylin, Lilly