A Study to Evaluate the Safety and Efficacy of Sitagliptin 100 mg in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control (MK-0431-229)

Study Overview
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Brief Summary
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This study will evaluate whether the addition of Sitagliptin treatment provides a greater decrease in A1C levels compared to placebo in participants with inadequate glycemic control on sulfonylurea and metformin combination therapy.

Official Title
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A Phase III, Randomized, Clinical Trial to Evaluate the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on a Sulfonylurea in Combination With Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin phosphate
* Drug: Comparator: placebo to pioglitazone
* Drug: Comparator: placebo to Sitagliptin
* Drug: Comparator: pioglitazone
* Drug: Glimepiride or gliclazide
* Drug: Metformin
* Drug: Pioglitazone rescue therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus Hemoglobin A1C of ≥7.5% and ≤10.5% Currently taking a stable dose of metformin (at least 1500 mg/day) and either glimepiride (at least 2 mg/day) or gliclazide (at least 50% of maximum registered dose) for at least 10 weeks prior to study start Male, or a female who is highly unlikely to conceive Exclusion Criteria: Type 1 diabetes mellitus or ketoacidosis Taking a dipeptidyl peptidase-4 (DPP-4) inhibitor (such as sitagliptin) or a glucagon-like peptide-1 (GLP-1) mimetic (such as exenatide or liraglutide) or required insulin therapy within 12 weeks prior to study start On a weight loss program not in the maintenance phase or on a weight loss medication History of liver disease, heart failure, heart disease, stroke, high blood pressure, blood disorders, or cancer HIV positive Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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 |
| --- | --- |
| Active Comparator: placebo/pioglitazone<br>Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): placebo to Sitagliptin 100 mg + pioglitazone 30 mg | Drug: Comparator: placebo to Sitagliptin<br>* Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): placebo to Sitagliptin once a day for 30 weeks<br>Drug: Comparator: pioglitazone<br>* Phase B (Weeks 24-54): pioglitazone 30 mg once a day for 30 weeks<br>* Other names: Actos;;Drug: Glimepiride or gliclazide<br>* Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of glimepiride or gliclazide; Phase B (Weeks 24-54): stable dose, as prescribed by investigator, of glimepiride or gliclazide<br>Drug: Metformin<br>* Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of metformin; Phase B (Weeks 24- 54): stable dose, as prescribed by investigator, of metformin<br>Drug: Pioglitazone rescue therapy<br>* Phase A (Weeks 0-24): participants not meeting specific glycemic goals will receive pioglitazone (open label) at a dose determined by the investigator. These participants will not initiate Phase B (Weeks 24-54) double blind pioglitazone.<br>* Other names: Actos;|
| Experimental: Sitagliptin<br>Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + placebo to pioglitazone | Drug: Sitagliptin phosphate<br>* Phase A (Weeks 0-24): Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): Sitagliptin 100 mg once a day for 30 weeks<br>* Other names: Januvia;Drug: Comparator: placebo to pioglitazone<br>* Phase B (Weeks 24-54): placebo to pioglitazone 30 mg once a day for 30 weeks<br>Drug: Glimepiride or gliclazide<br>* Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of glimepiride or gliclazide; Phase B (Weeks 24-54): stable dose, as prescribed by investigator, of glimepiride or gliclazide<br>Drug: Metformin<br>* Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of metformin; Phase B (Weeks 24- 54): stable dose, as prescribed by investigator, of metformin<br>Drug: Pioglitazone rescue therapy<br>* Phase A (Weeks 0-24): participants not meeting specific glycemic goals will receive pioglitazone (open label) at a dose determined by the investigator. These participants will not initiate Phase B (Weeks 24-54) double blind pioglitazone.<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1C (%) at Week 24 | Change from baseline reflects the Week 24 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin. | Baseline and Week 24 | 
| Number of Participants With One or More Adverse Events (AEs) - Week 0 to Week 54 |  | Week 0 to Week 54 | 
| Number of Participants Discontinuing Study Drug Due to An Adverse Event |  | Week 0 to Week 54 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2-hour Post-Meal Glucose at Week 24 | Change from baseline reflects the Week 24 value minus the baseline value. Two-hour post-meal glucose was measured following a standard meal. | Baseline and Week 24 | 
| Change From Baseline in Fasting Plasma Glucose at Week 24 | Change from baseline reflects the Week 24 value minus the baseline value. | Baseline to Week 24 | 

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