Bioequivalence Study of Sitagliptin/Metformin Combination Tablet (MK0431A-122)

Study Overview
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Brief Summary
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This study will test the hypothesis that the Final Market Image (FMI) sitagliptin/metformin 50 mg/500 mg and 50 mg/850 mg (Fixed Dose Combination) FDC tablet and co-administration of corresponding doses of sitagliptin and China-sourced metformin as individual tablets will be bioequivalent based on assessment of the AUC(0-t) and Cmax, for both sitagliptin and metformin.

Official Title
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A Bioequivalence Study With Two Tablet Strengths of the Final Market Image (FMI) Sitagliptin/Metformin Fixed Dose Combination (FDC) Tablet

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Co-administration of 50 mg sitagliptin and 500 mg metformin
* Drug: sitagliptin/metformin 50 mg/500 mg tablet
* Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin
* Drug: sitagliptin/metformin 50 mg/850 mg tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is of Chinese descent Subject is in good health Subject is a non-smoker Exclusion Criteria: Subject has a history of stroke or chronic seizures Subject has a history of cancer Subject has had major surgery, donated blood or participated in another investigational study within the past 4 weeks

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. Sit + Met500 / SitMet500 FDC / SitMet850 FDC / Sit + Met850<br>Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: Co-administration of 50 mg sitagliptin and 500 mg metformin sitagliptin/metformin 50 mg/500 mg FDC tablet sitagliptin/metformin 50 mg/850 mg FDC tablet Co-administration of 50 mg sitagliptin and 850 mg metformin | Drug: Co-administration of 50 mg sitagliptin and 500 mg metformin<br>* Co-administration of 50 mg sitagliptin and 500 mg China-sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met500) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/500 mg tablet<br>* Single dose administration of the final marketing image (FMI) sitagliptin/metformin 50 mg/500 mg fixed-dose combination (FDC) tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin<br>* Co-administration of 50 mg sitagliptin and 850 mg China sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met850) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/850 mg tablet<br>* Single dose administration of the FMI sitagliptin/metformin 50 mg/850 mg FDC tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>|
| Experimental: 2. SitMet500 FDC / Sit + Met850 / Sit + Met500 / SitMet850 FDC<br>Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: sitagliptin/metformin 50 mg/500 mg FDC tablet Co-administration of 50 mg sitagliptin and 850 mg metformin Co-administration of 50 mg sitagliptin and 500mg metformin sitagliptin/metformin 50 mg/850 mg FDC tablet | Drug: Co-administration of 50 mg sitagliptin and 500 mg metformin<br>* Co-administration of 50 mg sitagliptin and 500 mg China-sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met500) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/500 mg tablet<br>* Single dose administration of the final marketing image (FMI) sitagliptin/metformin 50 mg/500 mg fixed-dose combination (FDC) tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin<br>* Co-administration of 50 mg sitagliptin and 850 mg China sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met850) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/850 mg tablet<br>* Single dose administration of the FMI sitagliptin/metformin 50 mg/850 mg FDC tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>|
| Experimental: 3. Sit + Met850 / SitMet850 FDC / SitMet500 FDC / Sit + Met500<br>Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: Co-administration of 50 mg sitagliptin and 850 mg metformin sitagliptin/metformin 50 mg/850 mg FDC tablet sitagliptin/metformin 50 mg/500 mg FDC tablet Co-administration of 50 mg sitagliptin and 500mg metformin | Drug: Co-administration of 50 mg sitagliptin and 500 mg metformin<br>* Co-administration of 50 mg sitagliptin and 500 mg China-sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met500) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/500 mg tablet<br>* Single dose administration of the final marketing image (FMI) sitagliptin/metformin 50 mg/500 mg fixed-dose combination (FDC) tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin<br>* Co-administration of 50 mg sitagliptin and 850 mg China sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met850) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/850 mg tablet<br>* Single dose administration of the FMI sitagliptin/metformin 50 mg/850 mg FDC tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>|
| Experimental: 4. SitMet850 FDC / Sit + Met500 / Sit + Met850 / SitMet500 FDC<br>Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: sitagliptin/metformin 50 mg/850 mg FDC tablet Co-administration of 50 mg sitagliptin and 500 mg metformin Co-administration of 50 mg sitagliptin and 850 mg metformin sitagliptin/metformin 50 mg/500 mg FDC tablet | Drug: Co-administration of 50 mg sitagliptin and 500 mg metformin<br>* Co-administration of 50 mg sitagliptin and 500 mg China-sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met500) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/500 mg tablet<br>* Single dose administration of the final marketing image (FMI) sitagliptin/metformin 50 mg/500 mg fixed-dose combination (FDC) tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin<br>* Co-administration of 50 mg sitagliptin and 850 mg China sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met850) after fasting for at least 10 hours.<br>Drug: sitagliptin/metformin 50 mg/850 mg tablet<br>* Single dose administration of the FMI sitagliptin/metformin 50 mg/850 mg FDC tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC(0-t)) for Sitagliptin | AUC (0-t) is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg. | baseline through 72 hours postdose | 
| Cmax for Sitagliptin and Metformin | Cmax is the peak serum concentration of a therapeutic drug after administration; and is used to determine the rate and extent of drug absorption. Cmax is reported for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg. | baseline through 72 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes