A Study to Demonstrate the Bioequivalence of Sitagliptin/Metformin Combination Tablets and Concomitant Administration of Sitagliptin and Metformin as Individual Tablets (0431A-048)

Study Overview
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Brief Summary
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A two-part study to demonstrate the bioequivalence of a single dose of the Final Market Image (FMI) of sitagliptin /metformin (50/500 and 50/1000 mg) Fixed-Dose Combination (FDC) tablet and co-administration of a single dose of sitagliptin (50 mg) and metformin ( 500 or 1000 mg) as individual tablets. Subject will only participate in one part, receiving treatment A and B (Part I) or Treatment C and D (Part II).

Official Title
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An Open-label, Randomized Two-Part, Two-Period Crossover Study to Demonstrate the Definitive Bioequivalence After Administration of Final Market Image (FMI) Sitagliptin /Metformin 50/500 mg and 50/1000 mg Fixed Dose Combination (FDC) and Concomitant Administration of 50 mg Doses of Sitagliptin and 500 or 1000 mg Doses of Metformin as Individual Tablets

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: sitagliptin phosphate (+) metformin hydrochloride
* Drug: Comparator: metformin 500 mg
* Drug: Comparator: sitagliptin
* Drug: Comparator: FMI sitagliptin/metformin 50 mg/500 mg FDC tablet
* Drug: Comparator: FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet
* Drug: Comparator: metformin 1000 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects of reproductive potential test negative for pregnancy and agree to use appropriate contraception Subject is in good health and is a non-smoker Subject is willing to avoid strenuous physical activity during the study Subject agrees to refrain from eating grapefruit or grapefruit products during the study Exclusion Criteria: Subject has a history of neoplastic disease (cancer), stroke, chronic seizures, or major neurological disorder. Subject has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases Subject consumes excessive amounts of alcohol or caffeinated beverages Subject has donated blood, had surgery or participated in another clinical study within the past 4 weeks Subject has a history of significant multiple and/or severe allergies to prescription or non-prescription drugs or food Subject has a history of hypersensitivity to metformin, sitagliptin, or sitagliptin/Metformin Subject is a regular user or past abuser of any illicit drugs Subject is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies during the study. Subject is a nursing mother

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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br>Individual Tablets of 50 mg sitagliptin and 500 mg metformin | Drug: sitagliptin phosphate (+) metformin hydrochloride<br>* place holder - do not post<br>Drug: Comparator: metformin 500 mg<br>* A single dose of metformin 500 mg tablets<br>* Other names: Apotex;Drug: Comparator: sitagliptin<br>* A single 50 mg tablet of sitagliptin<br>|
| Experimental: Treatment B<br>Sitagliptin/metformin 50 mg/500 mg tablet | Drug: Comparator: FMI sitagliptin/metformin 50 mg/500 mg FDC tablet<br>* A single dose of FMI sitagliptin/metformin 50 mg/500 mg FDC tablet<br>|
| Active Comparator: Treatment C<br>Individual Tablets of 50 mg sitagliptin and 1000 mg metformin | Drug: Comparator: sitagliptin<br>* A single 50 mg tablet of sitagliptin<br>Drug: Comparator: metformin 1000 mg<br>* A single dose of metformin 1000 mg tablets<br>* Other names: Apotex;|
| Experimental: Treatment D<br>sitagliptin/metformin 50 mg/1000 mg tablet | Drug: Comparator: FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet<br>* A single dose of FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the plasma concentration vs. time curve (AUC) after administration of sitagliptin/metformin (50/500 and 50/1000 mg/mg) FDC tablet and co-administration of corresponding doses of sitagliptin and metformin as individual tablets |  | 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) of sitagliptin and metformin after administration of sitagliptin/metformin (50/500 and 50/1000 mg/mg) FDC tablet and co-administration of corresponding doses of sitagliptin and metformin as individual tablets |  | 72 hours post dose |