BE Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin HCl XR Tablet Relative to a 5 mg Saxagliptin (Onglyza™) Tablet and a 500 mg Metformin HCl XR (Glifage® XR Marketed in Brazil by Merck S.A.) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the bioequivalence (BE) of Saxagliptin and Metformin from a 5 mg Saxagliptin/500 mg Metformin extended release (XR) fixed dose combination (FDC) tablet relative to 5 mg Onglyza™ and 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) tablets administered together in both the fasted and fed states.

Detailed Description
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Primary purpose: To demonstrate the bioequivalence of Saxagliptin and Metformin from a 5 mg Saxagliptin/500 mg Metformin XR FDC tablet relative to 5 mg Onglyza™ and 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) tablets administered together in both the fasted and fed states.

Official Title
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Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin Hydrochloride (HCl) XR Tablet Relative to a 5 mg Saxagliptin (Onglyza™) Tablet and a 500 mg Metformin HCl XR (Glifage® XR Marketed in Brazil by Merck S.A.) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Metformin XR
* Drug: Saxagliptin/Metformin XR FDC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women Women of childbearing potential (WOCBP) who are using acceptable method of contraception Women who are not nursing Exclusion Criteria: History of Gastrointestinal (GI) disease Any GI surgery that could impact study drug absorption History of allergy to drug class or related compounds History of allergy to metformin or other similar acting agents. History of any significant drug allergy. Estimated creatinine clearance (ClCr) < 80 mL/min using Cockcroft-Gault formula

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A-Saxagliptin+Metformin XR<br>5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fasted state. | Drug: Saxagliptin<br>* Tablet, Oral, 5 mg, once on Day 1 only<br>* Other names: Onglyza;Drug: Metformin XR<br>* Tablet, Oral, 500 mg, once on Day 1 only<br>* Other names: Glifage XR;|
| Experimental: Treatment B-Saxagliptin/Metformin XR FDC<br>5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fasted state. | Drug: Saxagliptin/Metformin XR FDC<br>* Tablet, Oral, 5/500 mg, once on Day 1 only<br>* Other names: Onglyza/Glucophage;|
| Experimental: Treatment C-Saxagliptin+Metformin XR<br>5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fed state. | Drug: Saxagliptin<br>* Tablet, Oral, 5 mg, once on Day 1 only<br>* Other names: Onglyza;Drug: Metformin XR<br>* Tablet, Oral, 500 mg, once on Day 1 only<br>* Other names: Glifage XR;|
| Experimental: Treatment D-Saxagliptin/Metformin XR FDC<br>5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fed state. | Drug: Saxagliptin/Metformin XR FDC<br>* Tablet, Oral, 5/500 mg, once on Day 1 only<br>* Other names: Onglyza/Glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of BE on single-dose pharmacokinetic parameters maximum observed concentration (Cmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. |  | 48 hours after dosing | 
| Evidence of BE on single-dose pharmacokinetic parameters time of maximum observed concentration (Tmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. |  | 48 hours after dosing | 
| Evidence of BE on single-dose pharmacokinetic parameters (AUC(0-T) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. | Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T)) | 48 hours after dosing | 
| Evidence of BE on single-dose pharmacokinetic parameters area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. |  | 48 hours after dosing | 
| Evidence of BE on single-dose pharmacokinetic parameters half-life (T-HALF) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. |  | 48 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | 3 days after dosing | 
| Active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin, from 5 mg Saxagliptin/500 mg Metformin XR FDC tablet & from 5 mg Onglyza administered together with 500 mg Glifage® XR in single-dose fed & fasted state pharmacokinetics in healthy subjects | Amount of the active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin (BMS-510849), from the 5 mg Saxagliptin/500 mg Metformin XR FDC tablet and from 5 mg Onglyza™ administered together with 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) in single-dose fed and fasted state pharmacokinetics in healthy subjects | 3 days after dosing |