Bioavailability Study of Fixed Dose Combination (FDC) Formulations of Dapagliflozin and Metformin XR Versus Individual Component Coadministered to Healthy Subjects in a Fasted State

Study Overview
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Brief Summary
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To assess the relative bioavailability of dapagliflozin and metformin from the two FDC formulations, comprised of 10 mg dapagliflozin and 1000 mg metformin XR, relative to coadministration of a dapagliflozin 10 mg tablet and 2 x 500 mg Glucophage® XR tablets, in healthy subjects in a fasted state.

Official Title
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Bioavailability Study of Two Prototype Fixed Dose Combination (FDC) Formulations of 10 mg Dapagliflozin and 1000 mg Metformin Extended Release (XR) Tablet Relative to Dapagliflozin 10 mg Tablet and Glucophage® XR 2 X 500 mg Tablets Coadministered to Healthy Subjects in a Fasted State

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Metformin XR
* Drug: Glucophage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ages 18 to 45 inclusive Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2 Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product Any significant acute or chronic medical illness Current or recent (within 3 months) gastrointestinal disease Any major surgery within 4 weeks of study drug administration Glucosuria at screening Abnormal liver functions tests (ALT, AST or total bilirubin > 10% above ULN) Presence of edema on physical exam History of diabetes mellitus History of heart failure History of renal insufficiency History of chronic or recurrent UTI (defined as 3 occurrences per year) or UTI in the past 3 months History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal mycotic infections Estimated creatinine clearance (ClCR) of < 80 mL/min using the Cockcroft Gault formula History of allergy or intolerance to metformin or other similar agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: FDC of dapagliflozin/metformin XR<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Single Dose<br>Drug: Metformin XR<br>* Tablets, Oral, 1000 mg, Single Dose<br>|
| Other: FDC of dapagliflozin/reduced mass metformin XR<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Single Dose<br>Drug: Metformin XR<br>* Tablets, Oral, 1000 mg, Single Dose<br>|
| Other: dapagliflozin and Glucophage® XR<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 10 mg, Single Dose<br>Drug: Glucophage<br>* Tablets, Oral, 1000 mg, Single Dose<br>* Other names: Glucophage™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood samples to measure the pharmacokinetic parameters Cmax and AUC for the combination products versus each investigational product alone |  | 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability measures (adverse events, physical exams, vital signs, ECGs, and clinical laboratory assessments) |  | 15 timepoints in 48 hours time interval |