Study of Safety and Efficacy of PF-04991532 in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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B2611003 is designed to study how safe and effective an investigational medication (PF-04991532) is in people with Type 2 diabetes. Subjects in the study will receive 1 of 6 treatments for 3 months. One of the treatments will be sitagliptin which is an approved drug, and another treatment will be placebo, which does not contain active ingredient.

Official Title
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A 12-week, Phase 2, Randomized, Double-blind, Placebo Controlled, Dose-ranging, Parallel Group Study to Evaluate the Efficacy and Safety of Twice Daily Pf-04991532 and Once Daily Sitagliptin in Adult Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: 25 mg PF-04991532
* Drug: 75 mg PF-04991532
* Drug: 150 mg PF-04991532
* Drug: 300 mg PF-04991532
* Drug: Sitagliptin 100 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with type 2 diabetes on stable doses of background medicines for management of diabetes; aged 18-70 years; body mass index between 22.5 and 45.5 kg/m2 Exclusion Criteria: Subjects with type 1 diabetes, heart attack or stroke in the past 6 months, uncontrolled blood pressure, significant kidney disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo for PF-04991532 and sitagliptin | Drug: Placebo<br>* Tablets (n=4), 0 mg twice daily for 84 days<br>|
| Experimental: 25 mg PF-04991532<br> | Drug: 25 mg PF-04991532<br>* Tablets (n=1), 25 mg strength + tablets (n=3) 0 mg twice daily for 84 days<br>|
| Experimental: 75 mg PF-04991532<br> | Drug: 75 mg PF-04991532<br>* Tablets (n=3), 25 mg strength + tablets (n=1) 0 mg twice daily for 84 days<br>|
| Experimental: 150 mg PF-04991532<br> | Drug: 150 mg PF-04991532<br>* Tablets (n=1), 150 mg strength + tablets (n=3) 0 mg twice daily for 84 days<br>|
| Experimental: 300 mg PF-04991532<br> | Drug: 300 mg PF-04991532<br>* Tablets (n=2), 150 mg strength + tablets (n=2) 0 mg twice daily for 84 days<br>|
| Active Comparator: Sitagliptin 100 mg<br> | Drug: Sitagliptin 100 mg<br>* Tablets (n=1), 100 mg strength + tablets (n=3) 0 mg once daily in the morning for 84 days; and tablets (n=4) 0 mg once daily in the evening for 84 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4 percent (%) and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose at Week 1, 2, 4, 8 and 12 |  | Baseline, Week 1, 2, 4, 8, 12 | 
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 1, 2, 4 and 8 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes. | Baseline, Week 1, 2, 4, 8 | 
| Percentage of Participants Achieving Less Than (<) 6.5% or <7% Glycosylated Hemoglobin (HbA1c) Levels | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes, and levels of 6.5% or higher indicate diabetes. | Week 12 | 
| Change From Baseline in Body Weight at Week 1, 2, 4, 8 and 12 | Overweight or obesity increases the risk for developing diabetes. The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c. | Baseline, Week 1, 2, 4, 8, 12 | 
| Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Gain in Body Weight From Baseline | Overweight or obesity increases the risk for developing diabetes. Participants with >= 1% or >= 2% gain in body weight from baseline signifies a higher risk of diabetes. | Week 12 | 
| Percentage of Participants With Greater Than or Equal to (>=) 1% or >= 2% Loss in Body Weight From Baseline | The treatment of diabetes has been the recommendation to lose weight. As weight loss progresses and is maintained, an improvement of glycemia may be evidenced by a reduction in HbA1c. Participants with >= 1% or >= 2% loss in body weight from baseline signifies an improvement of glycemia. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety and efficacy study with PF-04991532, Type 2 diabetes, Phase 2