Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052)

Study Overview
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Brief Summary
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A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin/peroxisome proliferator-activated receptor gamma (PPARg) agonist combination therapy.

Official Title
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A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and a PPARg Agonist

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: sitagliptin
* Drug: Comparator: Placebo
* Drug: rosiglitazone
* Drug: metformin
* Drug: glipizide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has type 2 diabetes mellitus Patient is inadequately controlled while taking two oral antidiabetic medications Exclusion Criteria: Patient has a history of type 1 diabetes mellitus or history of ketoacidosis Patient required insulin therapy within the prior 3 months Patient has been taking Byetta (R) (exenatide) within the prior 3 months

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: 1<br>Sitagliptin | Drug: sitagliptin<br>* Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.<br>* Other names: Januvia;Drug: rosiglitazone<br>* Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.<br>* Other names: Avandia;Drug: metformin<br>* Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.<br>Drug: glipizide<br>* Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.)<br>* Other names: Glucotrol;|
| Placebo Comparator: 2<br>Placebo | Drug: Comparator: Placebo<br>* Placebo to sitagliptin 100mg tablet each day for 54 weeks.<br>Drug: rosiglitazone<br>* Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.<br>* Other names: Avandia;Drug: metformin<br>* Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.<br>Drug: glipizide<br>* Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.)<br>* Other names: Glucotrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18 | HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. | Baseline and 18 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18 | Change from baseline at Week 18 is defined as Week 18 minus Week 0 | Baseline and 18 Weeks | 
| Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18 | Change from baseline at Week 18 is defined as Week 18 minus Week 0 | Baseline and Week 18 | 
| Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 | HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent. | Baseline and Week 54 | 
| Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0 | Baseline and Week 54 | 
| Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. | Baseline and Week 54 | 

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