A Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration

Study Overview
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Brief Summary
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The primary objective of this study is to assess the pharmacokinetic parameters of saxagliptin and metformin in healthy male Chinese subjects.

Detailed Description
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A Single-centre, Randomized, Open-label, Two-period, Cross-over, Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration of the Individual Components in two cohorts of Healthy Chinese Subjects under Fed Conditions

Official Title
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A Single-centre, Randomized, Open-label, Two-period, Cross-over, Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration of the Individual Components in Two Cohorts of Healthy Chinese Subjects Under Fed Conditions

Conditions
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Type 2 Diabetes Mellitus(T2DM)

Intervention / Treatment
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* Drug: Saxagliptin 5 mg
* Drug: Metformin XR 500 mg
* Drug: Mertformin XR 2 x 500 mg
* Drug: Komboglyze XR 5/500 mg
* Drug: Komboglyze XR 5/1000 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese ethnicity which is defined as having both parents and 4 grandparents who are Chinese Healthy male subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations Men, ages 18 to 40 years, inclusive. The age difference among the subjects is within 10 years Weigh at least 50 kg and have a body mass index (BMI) between 19 and 24 kg/m2 Sexually active fertile men must use effective birth control throughout the study and for up to 90 days after the last dose of investigational product if their partners are women of child bearing potential Exclusion Criteria: Any significant acute or chronic medical illness Current or recent gastrointestinal disease Subjects that have lymphocytopenia or thrombocytopenia History of autoimmune skin disorder Estimatedcreatinine clearance of less than 80 mL/min

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower dose<br>co-administration of a single oral dose of a 5 mg saxagliptin tablet and a 500 mg metformin XR (Glucophage XR®) tablet vs. single FDC tablet consisting of 5 mg saxagliptin and 500 mg metformin XR (Kombiglyze XR) | Drug: Saxagliptin 5 mg<br>* Saxagliptin oral tablet 5mg, single dose<br>Drug: Metformin XR 500 mg<br>* Metformin XR oral tablet 500 mg, single dose<br>Drug: Komboglyze XR 5/500 mg<br>* oral FDC tablet (saxagliptin 5 mg and metformin 500 mg), single dose<br>|
| Experimental: Higher dose<br>co-administration of a single oral dose of a 5 mg saxagliptin tablet and two (2) 500 mg metformin XR (Glucophage XR®) tablets vs. Single FDC tablet consisting of 5 mg saxagliptin and 1000 mg metformin XR (Kombiglyze XR) | Drug: Saxagliptin 5 mg<br>* Saxagliptin oral tablet 5mg, single dose<br>Drug: Mertformin XR 2 x 500 mg<br>* Metformin XR oral tablet 2 x 500 mg, single dose<br>Drug: Komboglyze XR 5/1000 mg<br>* oral FDC tablet (saxagliptin 5 mg and metformin 1000 mg), single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) for saxagliptin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets |  | Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose | 
| Maximum plasma concentration (Cmax) for metformin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets |  | Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose | 
| Area under plasma concentration time curve (AUC) for saxagliptin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets |  | Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose | 
| Area under plasma concentration time curve (AUC) for metformin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets |  | Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) for 5-hydroxy saxagliptin |  | Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose | 
| Area under plasma concentration time curve (AUC) for 5-hydroxy saxagliptin |  | Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose | 
| Safety and tolerability assessment based on medical review of AE reports:physical examination, ECG, heart rate, blood pressure, lab test | Assessment for 5 mg saxagliptin co-administered with up to 1000 mg metformin XR given either separately, or as a single FDC tablet. | Study duration for individual subject (up to 34 days) when the safety data are collected | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, Saxagliptin, Metformin,Fixed dose combination tablet, Bioequivalence, pharmacokinetic, safety, tolerability