A Study to Evaluate the Efficacy and Safety of Sitagliptin and MK0431A in Comparison to a Commonly Used Medication in Patients With Type 2 Diabetes (0431-068)(COMPLETED)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of sitagliptin and MK0431A in comparison to a commonly used medication in patients with type 2 diabetes.

Official Title
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A Phase III Randomized, Active-Comparator (Pioglitazone) Controlled Clinical Trial to Study the Efficacy and Safety of Sitagliptin and MK0431A (A Fixed-Dose Combination Tablet of Sitagliptin and Metformin) in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Comparator: sitagliptin phosphate (sitagliptin)
* Drug: sitagliptin phosphate (+) metformin hydrochloride
* Drug: Comparator: pioglitazone
* Drug: Matching placebo to pioglitazone
* Drug: Matching placebo to sitagliptin
* Drug: Matching Placebo to Sita/Met FDC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between the ages of 18 and 78 with type 2 diabetes mellitus Patient has not been on any antihyperglycemic agent (Insulin or oral) in the last 3 months Exclusion Criteria: Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis Patient has previously been treated with sitagliptin or has previously been in a study using a DPP-4 inhibitor

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 |
| --- | --- |
| Experimental: Sita/Met FDC<br>In Phase A (Treatment Day 1 to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to 15 mg pioglitazone q.d. for 6 weeks followed by matching placebo to 30 mg pioglitazone for the next 6 weeks. In Phase B (Treatment Week 12-Week 40), participants were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks; as well as matching placebo to 45 mg pioglitazone. | Drug: Comparator: sitagliptin phosphate (sitagliptin)<br>* sitagliptin 100 mg tablet q.d. orally for a 12-wk treatment period<br>* Other names: MK0431, Januvia™;Drug: sitagliptin phosphate (+) metformin hydrochloride<br>* sitagliptin/metformin HCl (Sita/Met) 50/500 mg b.i.d. orally and then 50/1000 mg b.i.d. orally for a 28-wk treatment period<br>* Other names: MK-0431A, Janumet™;Drug: Matching placebo to pioglitazone<br>* matching placebo to pioglitazone tablet q.d. orally, for a 40-wk treatment period. Participants were administered matching placebo the 15 mg pioglitazone q.d. orally for 6 weeks, followed by matching placebo to 30 mg pioglitazone q.d orally for 6 weeks, followed by matching placebo to 45 mg pioglitazone q.d. orally, up to 40 weeks.<br>|
| Active Comparator: Pioglitazone<br>In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone and matching placebo to sitagliptin. At Week 6, participants were up-titrated to 30 mg pioglitazone q.d. In Phase B (Treatment Week 12 to Week 40), participants were administered 45 mg pioglitazone q.d.; as well as matching placebo to Sita/Met FDC (50/500 increased to 50/1000 b.i.d. after 4 weeks). | Drug: Comparator: pioglitazone<br>* pioglitazone 15 mg tablet q.d. orally for 6 weeks, followed by 30 mg q.d orally for 6 weeks, followed by 45 mg q.d. orally, up to 40 weeks.<br>* Other names: Actos®;Drug: Matching placebo to sitagliptin<br>* matching placebo to sitagliptin q.d., orally for a 12-wk treatment period.<br>Drug: Matching Placebo to Sita/Met FDC<br>* matching placebo to Sita/Met FDC - 50/500 mg b.i.d. for 4 weeks and then 50/1000 mg b.i.d. orally for a 28-wk treatment period (Week 12 to Week 40).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin A1c (A1C) in the Sita/Met Fixed-Dose Combination (FDC) or Pioglitazone Groups at 40 Weeks | The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin. | Baseline to 40 weeks | 
| Change in Hemoglobin A1c (A1C) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | The change in A1C compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. A1c represents percentage of glycosylated hemoglobin. | Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 2-hour Postprandial Glucose (PMG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the Sita/Met FDC and the pioglitazone groups at Week 40. | Baseline and 40 weeks | 
| Change in 2-hour Postprandial Glucose (PMG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | The change in PMG compared to baseline was measured using the Meal Tolerance Test (MTT) for the participants treated with Sitagliptin or Pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate. | Baseline to 12 weeks | 
| Change in Fasting Plasma Glucose (FPG) in the Sita/Met FDC or Pioglitazone Groups at 40 Weeks | The change in FPG compared to baseline was measured for the Sita/Met FDC and the pioglitazone groups at Week 40. | Baseline and 40 weeks | 
| Change in Fasting Plasma Glucose (FPG) in Participants Treated With Sitagliptin or Pioglitazone at 12 Weeks | The change in FPG compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. To calculate Least Squares, the ANCOVA model included a term for treatment and the baseline value as a covariate. | Baseline to 12 weeks |