A Study to Demonstrate the Bioequivalence of Sitagliptin/Metformin Combination Tablets and Co-administration of Sitagliptin and Metformin as Individual Tablets (0431A-095)

Study Overview
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Brief Summary
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A three part study to demonstrate the bioequivalence of a single dose of the Final Market Image (FMI) of sitagliptin/metformin 50/500, 50/850 and 50/1000 mg Fixed-Dose Combination (FDC) tablet and co-administration of corresponding doses of sitagliptin and metformin as individual tablets. Subject will only participate in one part, receiving treatment A and B (Part I), Treatment C and D (Part II) or Treatment E and F (Part III).

Official Title
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A 3-Part, Open-Label, Randomized, 2-Period Crossover Study to Demonstrate the Definitive Bioequivalence After Administration of the FMI Sitagliptin/Metformin 50/500 mg, 50/850 mg and 50/1000 mg FDC Tablet and Co-administration of Corresponding Doses of Sitagliptin and 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 500mg
* 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: FMI sitagliptin/metformin 50 mg/850 mg FDC tablet
* Drug: Comparator: metformin 1000 mg
* Drug: Comparator: metformin 850 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 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 is a nursing mother Subject consumes excessive amounts of alcohol or caffeine Subject has donated blood, had surgery or participated in another clinical study within the past 4 weeks

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

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>50 mg sitagliptin and 500 mg metformin as individual tablets | Drug: sitagliptin phosphate (+) metformin hydrochloride<br>* place holder - do not post<br>Drug: Comparator: metformin 500mg<br>* A single dose of metformin 500 mg tablet<br>* Other names: Glucophage;Drug: Comparator: sitagliptin<br>* A single dose of 50 mg sitagliptin tablet<br>* Other names: Januvia;|
| 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>50 mg sitagliptin and 1000 mg metformin as individual tablets | Drug: Comparator: sitagliptin<br>* A single dose of 50 mg sitagliptin tablet<br>* Other names: Januvia;Drug: Comparator: metformin 1000 mg<br>* A single dose of metformin 1000 mg tablet<br>* Other names: Glucophage;|
| 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>|
| Active Comparator: Treatment E<br>50 mg sitagliptin and 850 mg metformin as individual tablets | Drug: Comparator: sitagliptin<br>* A single dose of 50 mg sitagliptin tablet<br>* Other names: Januvia;Drug: Comparator: metformin 850 mg<br>* A single dose of metformin 850 mg tablet<br>* Other names: Glucophage;|
| Experimental: Treatment F<br>sitagliptin/metformin 50 mg/850 mg tablet | Drug: Comparator: FMI sitagliptin/metformin 50 mg/850 mg FDC tablet<br>* A single dose of FMI sitagliptin/metformin 50 mg/850 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-time curve (AUC) after administration of sitagliptin/metformin (50/500; 50/850; 50/1000 mg/mg) FDC tablet and co-administration of corresponding doses of sitagliptin and metformin as individual tablets. |  | Up to 72 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) for metformin after administration of sitagliptin/metformin (50/500; 50/850, 50/1000 mg/mg) FDC tablet and co-administration of corresponding doses of sitagliptin and metformin as individual tablets. |  | Up to 72 hours postdose |