Sitagliptin (MK-0431) vs. Placebo in Patients With Inadequate Glycemic Control on Metformin With Pioglitazone (MK-0431-128)

Study Overview
=================
Brief Summary
-----------------
This study will examine the safety and efficacy of the addition of sitagliptin (MK-0431) compared to placebo in patients with type 2 diabetes mellitus with inadequate glycemic control who are taking pioglitazone and metformin.

Official Title
-----------------
A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK-0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and Pioglitazone

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Sitagliptin
* Drug: Comparator: Placebo
* Drug: Pioglitazone
* Drug: Metformin
* Drug: Glipizide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: has type 2 diabetes and is at least 18 years of age and no older than 78 years of age is male or is a female who is unlikely to conceive children is on stable doses of a peroxisome proliferator-activated receptor gamma agonist and metformin OR metformin and a sulfonylurea agent Exclusion Criteria: has type 1 diabetes has taken a dipeptidyl peptidase (DPP-4) inhibitor or a glucagon-like peptide-1 (GLP-1) analogue is on a weight loss program that is not in the maintenance phase or has started a weight loss medication within 8 weeks of screening has had surgery within 30 days of screening or has major surgery planned during the study is on or is likely to require treatment with corticosteroids for more than 2 weeks has a history of active liver disease, including hepatitis B or C, cirrhosis, or gallbladder disease is human immunodeficiency virus (HIV) positive has congestive heart failure, or has had new or worsening symptoms of coronary heart disease within 3 months prior to screening has had acute coronary syndrome, coronary artery intervention, or stroke within 3 months of screening has severe active peripheral vascular disease has a history of cancer or blood disorder is pregnant or breast feeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 78 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin<br>Sitagliptin 100 mg tablet orally once daily for 26 weeks. | Drug: Sitagliptin<br>* Sitagliptin 100 mg tablet orally once daily for 26 weeks.<br>* Other names: MK-0431;Drug: Pioglitazone<br>* Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks.<br>* Other names: Actos;Drug: Metformin<br>* Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks.<br>* Other names: Glucophage;Drug: Glipizide<br>* Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country.<br>* Other names: Glucotrol;|
| Placebo Comparator: Placebo<br>Placebo to sitagliptin orally once daily for 26 weeks. | Drug: Comparator: Placebo<br>* Placebo to sitagliptin 100 mg tablet orally once daily for 26 weeks.<br>Drug: Pioglitazone<br>* Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks.<br>* Other names: Actos;Drug: Metformin<br>* Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks.<br>* Other names: Glucophage;Drug: Glipizide<br>* Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country.<br>* Other names: Glucotrol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (A1C) at Week 26 | Change from baseline reflects the Week 26 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin. | Baseline and Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2-Hour Post-Meal Glucose (PMG) at Week 26 | Change from baseline reflects the Week 26 value minus the baseline value. | Baseline and Week 26 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | Change from baseline reflects the Week 26 value minus the baseline value. | Baseline and Week 26 |