Bioequivalence Study

Study Overview
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Brief Summary
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The purpose of this study is to determine if tablets manufactured at different sites have the same bioavailability, that is yield similar blood levels/concentrations of the drugs and are handled by the body similarly

Detailed Description
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Primary Purpose: Other: Protocol designed to demonstrate the bioequivalence of the fixed dose combination of 5 mg Saxagliptin and 1000 mg Metformin Extended Release Tablet manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico relative to the fixed dose combination tablet manufactured in Mt. Vernon, Indiana and the bioequivalence of the fixed dose combination of 5 mg Saxagliptin and 500 mg Metformin Extended Release Tablet manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico relative to the fixed dose combination tablet manufactured in Mt. Vernon, Indiana in healthy human subjects under fed conditions

Official Title
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Bioequivalence Study of the Fixed Dosed Combination of 5 mg Saxagliptin and 1000 mg Metformin Extended Release Tablet Manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico Relative to the Fixed Dosed Combination Tablet Manufactured in Mt. Vernon, Indiana and Bioequivalence Study of the Fixed Dosed Combination of 5 mg Saxagliptin and 500 mg Metformin Extended Release Tablet Manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico Relative to the Fixed Dosed Combination Tablet Manufactured in Mt. Vernon, Indiana Administered to Healthy Subjects Under Fed Conditions

Conditions
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Diabetes

Intervention / Treatment
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* Drug: Saxagliptin/Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects, 18-45 years of age Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive Women must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product Exclusion Criteria: Any significant acute or chronic medical illness Estimated creatinine clearance of <60 mL/min as calculated using the Modification of Diet in Renal Disease method Current or recent (within 3 months of study drug administration) Gastrointestinal (GI) disease that could affect the absorption of study drug Inability to tolerate oral medication History of allergies or adverse reactions to DPP4 inhibitors or Metformin or related compounds Current smoker or recent (within 6 months of study drug administration) history of regular tobacco use (positive cotinine test)

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 |
| --- | --- |
| Experimental: Arm A: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao)<br>Saxagliptin 5 mg /Metformin 1000 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day 1 of Periods 1 and 2 | Drug: Saxagliptin/Metformin<br> <br> * Other names: Kombiglyze XR;|
| Experimental: Arm B: Saxagliptin/Metformin XR FDC (Mt. Vernon)<br>Saxagliptin 5 mg/Metformin 1000 mg (Mt. Vernon) tablet by mouth once daily on Day 1 of Periods 1 and 2 | Drug: Saxagliptin/Metformin<br> <br> * Other names: Kombiglyze XR;|
| Experimental: Arm C: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao)<br>Saxagliptin 5 mg/Metformin 500 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day1 of Periods 1 and 2 | Drug: Saxagliptin/Metformin<br> <br> * Other names: Kombiglyze XR;|
| Experimental: Arm D: Saxagliptin/Metformin XR FDC (Mt. Vernon)<br>Saxagliptin 5 mg/Metformin 500 mg (Mt. Vernon) tablet by mouth once daily Day 1 of Periods 1 and 2 | Drug: Saxagliptin/Metformin<br> <br> * Other names: Kombiglyze XR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point estimates and 90% CIs for the ratio of geometric means for Cmax for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) | Cmax=Maximum observed plasma concentration CI=Confidence interval FDC=Fixed dosed combination XR=Extended release | 19 time points up to Day 3 of Periods 1 and 2 | 
| Point estimates and 90% CIs for the ratio of geometric means for AUC(0-T) for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) | AUC(0-T)=Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration | 19 time points up to Day 3 of Periods 1 and 2 | 
| Point estimates and 90% CIs for the ratio of geometric means for AUC(INF) for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) | AUC(INF)=Area under the plasma concentration-time curve from time zero extrapolated to infinity | 19 time points up to Day 3 of Periods 1 and 2 | 
| Point estimates and 90% CIs for the ratio of geometric means for Cmax for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| Point estimates and 90% CIs for the ratio of geometric means for AUC(0-T) for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| Point estimates and 90% CIs for the ratio of geometric means for AUC(INF) for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) |  | 19 time points up to Day 3 of Periods 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum observed plasma concentration (Tmax) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| Terminal half life (T-HALF) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| Cmax for 5-OH Saxagliptin (Treatments A, B, C, and D) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| AUC(0-T) for 5-OH Saxagliptin (Treatments A, B, C, and D) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| AUC(INF) for 5-OH Saxagliptin (Treatments A, B, C, and D) |  | 19 time points up to Day 3 of Periods 1 and 2 | 
| Safety assessments based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests | Parameters will include: Serious adverse events Deaths Adverse events leading to discontinuation Number of subjects with potentially clinically significant changes in vital signs, electrocardiograms (ECGs) or safety laboratory findings defined as meeting marked abnormality criteria | Up to Day 3 of Periods 1 and 2 and up to 30 days post discontinuation of dosing |