Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus (0431-061)

Study Overview
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Brief Summary
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A clinical study to determine the safety, efficacy and mechanism of action of sitagliptin alone and in combination with pioglitazone, in patients with type 2 diabetes mellitus who have inadequate glycemic (blood sugar) control.

Official Title
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A Phase I Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Study the Safety, Efficacy, and Mechanism of Action of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet and Exercise

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: Comparator: sitagliptin phosphate
* Drug: Comparator: pioglitazone
* Drug: Comparator: placebo to pioglitazone
* Drug: Comparator: placebo to sitagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has type 2 diabetes mellitus Male Female that is highly unlikely to become pregnant Patient is not on an antihyperglycemic agent (AHA) (hemoglobin A1c [A1C] 7-10%) or on oral single AHA or low-dose combination therapy (A1C 6.5-9.0%) Exclusion Criteria: Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis Patient has required insulin therapy within the past 12 weeks Patient is on or has been taking a Peroxisome Proliferator-Activated Receptor-gamma (PPAR -gamma) agent (i.e. Thiazolidinediones [TZDs]) within the prior 12 weeks of the screening visit.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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>Arm 1: drug | Drug: Comparator: sitagliptin phosphate<br>* sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily.<br>Drug: Comparator: placebo to pioglitazone<br>* pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.<br>|
| Active Comparator: 2<br>Arm 2: active comparator | Drug: Comparator: pioglitazone<br>* pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.<br>Drug: Comparator: placebo to sitagliptin<br>* sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.<br>|
| Experimental: 3<br>Arm 3: drug + active comparator | Drug: Comparator: sitagliptin phosphate<br>* sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily.<br>Drug: Comparator: pioglitazone<br>* pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.<br>|
| Placebo Comparator: 4<br>Arm 4: placebo comparator | Drug: Comparator: placebo to pioglitazone<br>* pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.<br>Drug: Comparator: placebo to sitagliptin<br>* sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment | Glucagon concentration was measured at 9 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, and 180 minutes. Total AUC was calculated over 3 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC. | Baseline and 12 weeks | 
| Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment | Static sensitivity is a measure of the effect of glucose on beta cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state. Percent change from baseline was calculated as the difference between index of static sensitivities at Week 12 and at baseline with respect to the index of static sensitivity at baseline times 100. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment | Glucose concentration was measured at 11 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, 180, 240, 300 minutes. Total AUC was calculated over 5 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus (T2DM)