A Phase IIA Study of BMS-512148 to Assess Safety, Exposure, and Biological Effects in Stable Type 2 Diabetic Subjects

Study Overview
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Brief Summary
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The purpose of this clinical research study is to assess the safety of, exposure to, and biological effects of BMS-512148 in stable Type 2 diabetic subjects

Official Title
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A Double-blind, Placebo-controlled, Randomized, Multiple-dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Bms-512148 in Diabetic Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BMS-512148
* Drug: BMS-512148
* Drug: BMS-512148
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of Type 2 diabetes mellitus, who are treated with metformin or diet alone (drug naive). Fasting glucose (FG) < - 240 mg/dL, while on metformin or antidiabetic diet alone. HbA1c (Hemoglobin A1c) in the range of 6.0-10.0% Exclusion Criteria: Women of childbearing potential

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 |
| --- | --- |
| Active Comparator: 1<br> | Drug: BMS-512148<br>* Capsules, Oral, 100 mg, Once daily, 14 days.<br>* Other names: Dapagliflozin;|
| Active Comparator: 2<br> | Drug: BMS-512148<br>* Capsules, Oral, 25 mg, Once daily, 14 days.<br>* Other names: Dapagliflozin;|
| Active Comparator: 3<br> | Drug: BMS-512148<br>* Capsules, Oral, 5 mg, Once daily, 14 days.<br>* Other names: Dapagliflozin;|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* Capsules, Oral, 0 mg, Once daily, 14 days.<br>* Other names: Dapagliflozin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of multiple oral doses of BMS-512148 administered alone or concomitantly with metformin in diabetic subjects | Adverse event monitoring, physical examinations, clinical laboratory determinations, electrocardiograms (ECG), and vital sign assessments | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the PK of BMS-512148 and its pharmacologically active metabolite, BMS-511926, when BMS-512148 is administered alone or concomitantly with metformin | Exposure to BMS-512148 and BMS-511926 | 14 days | 
| To assess the pharmacodynamic effect of BMS-512148, administered alone or concomitantly with metformin, on serum and urine markers of glucose homeostasis | Fasting and post-prandial serum glucose, serum fructosamine, serum insulin, and serum C-peptide and urinary glucose and urinary calcium | 14 days | 
| To assess the effect of BMS-512148, administered alone or concomitantly with metformin, on safety markers in urine | calcium, magnesium, sodium, potassium, phosphate, chloride, uric acid, oxalate, citrate, total protein, albumin, osmolality, deoxypyridinoline (D-pyr) cross-links, C-telopetide (CTX), N-acetyl-β- D-glucoasaminidase (NAG), and β2-microglubulin (β2-MG) | 14 days | 
| To assess the effect of BMS-512148, administered alone or concomitantly with metformin, on the following safety markers in serum | Serum osteocalcin, parathyroid hormone (PTH), 25-Vitamin D, and 1,25-Vitamin D | 14 days | 
| To assess the effect of BMS-512148 administered alone or concomitantly with metformin on the percent inhibition of renal glucose reabsorption | Percent inhibition of renal glucose resorption over each 0-4 h, 4-8 h, and 8-12 h post-dose interval calculated from the amount of renally filtered glucose and the amount of glucose excreted in the urine for each collection interval. | 14 days | 
| To assess the effects of BMS-512148 on the PK of metformin in diabetic subjects. | Exposure to metformin | 14 days | 
| To identify potential biomarkers in both urine and blood | Serum and urine for metabonomic assessment | 14 days |