A 6-Week Study To Determine The Safety And Effect Of An Investigational Drug Given With Canagliflozin In Adults With Type 2 Diabetes Mellitus Taking Metformin

Study Overview
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Brief Summary
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A Phase 2a study to evaluate the effects of an investigational compound administered at 200 mg, twice daily (BID), for 6 weeks, with canagliflozin, in adult subjects with Type 2 Diabetes Mellitus (T2DM).

Official Title
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A 6-week Phase 2a Randomized, Double-Blind, Placebo-Controlled Study To Assess Safety, Tolerability And Pharmacodynamics Of Oral PF-05175157 Administered With Canagliflozin In Adult Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: PF-05175157
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Type 2 Diabetes Mellitus and treated with metformin at a dose greater than or equal to 1000 mg for at least 3 months and are willing to switch to canagliflozin from metformin for the duration of the study Hemoglobin A1c of 7-10% at screening. Body Mass Index of at least 25 kg/m2. Exclusion Criteria: Compliant with study drug administration during the run-in period and throughout the trial. Patients with fasting triglycerides greater than 500 mg/dL at screening. History of certain diabetic complications or cardiac problems.

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-05175157<br> | Drug: PF-05175157<br>* Tablet, 200 mg, twice daily, 6 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tablet, 0 mg, twice daily, 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Weighted Mean Daily Glucose (WMDG) when compared to placebo |  | Week 0, 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Weighted Mean Daily Glucose (WMDG) when compared to placebo |  | Weeks 0 and 4 | 
| Change from baseline in fasting plasma glucose |  | Weeks 0, 2, 4 and 6 | 
| Change from baseline in Glycosylated Hemoglobin (HbA1c) |  | Weeks 0, 4 and 6 | 
| Change from baseline in fasting total cholesterol |  | Weeks 0, 4 and 6 | 
| Change from baseline in glucose AUC(0-5) during mixed meal tolerance test (MMTT) |  | Weeks 0, 4 and 6 | 
| Change from baseline in insulin AUC(0-5) during mixed meal tolerance test (MMTT) |  | Weeks 0, 4 and 6 | 
| Change from baseline in C-peptide AUC(0-5) during mixed meal tolerance test (MMTT) |  | Weeks 0, 4 and 6 | 
| Change from baseline in ratio of AUC(0-5) insulin to AUC(0-5) glucose during the MMTT |  | Weeks 0, 4 and 6 | 
| Change from baseline in ratio of AUC (0-5) C-peptide to AUC(0-5) glucose during the MMTT |  | Weeks 0, 4 and 6 | 
| Change from baseline in homeostatic model assessment for insulin resistance (HOMA IR) |  | Weeks 0, 4 and 6 | 
| Change from baseline in homeostatic model assessment for β-cell function (HOMA B) |  | Weeks 0, 4 and 6 | 
| Change from baseline in low density lipoprotein cholesterol (LDL-C) |  | Weeks 0, 4 and 6 | 
| Plasma concentrations for PF-05175157 |  | Weeks 2, 4 and 6 | 
| Percent change from baseline in body weight |  | Weeks 0, 4 and 6 | 
| Change from baseline in high density lipoprotein cholesterol (HDL-C) |  | Weeks 0, 4 and 6 | 
| Change from baseline in triglycerides |  | Weeks 0, 4 and 6 | 
| Change from baseline in non-HDL cholesterol |  | Weeks 0, 4 and 6 | 
| Change from baseline in very low density lipoprotein (VLDL) |  | Weeks 0, 4 and 6 |