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

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: 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: metformin 1000 mg; Drug: Comparator: FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet; Drug: Comparator: metformin 850 mg; Drug: Comparator: FMI sitagliptin/metformin 50 mg/850 mg FDC tablet

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; 50 mg sitagliptin and 500 mg metformin as individual tablets	Drug: sitagliptin phosphate (+) metformin hydrochloride; place holder - do not post; Drug: Comparator: metformin 500mg; A single dose of metformin 500 mg tablet; Other Names: Glucophage; Drug: Comparator: sitagliptin; A single dose of 50 mg sitagliptin tablet; Other Names: Januvia
Experimental: Treatment B; sitagliptin/metformin 50 mg/500 mg tablet	Drug: Comparator: FMI sitagliptin / metformin 50 mg/500 mg FDC tablet; A single dose of FMI sitagliptin/metformin 50 mg/500 mg FDC tablet
Active Comparator: Treatment C; 50 mg sitagliptin and 1000 mg metformin as individual tablets	Drug: Comparator: sitagliptin; A single dose of 50 mg sitagliptin tablet; Other Names: Januvia; Drug: Comparator: metformin 1000 mg; A single dose of metformin 1000 mg tablet; Other Names: Glucophage
Experimental: Treatment D; sitagliptin/metformin 50 mg/1000 mg tablet	Drug: Comparator: FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet; A single dose of FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet
Active Comparator: Treatment E; 50 mg sitagliptin and 850 mg metformin as individual tablets	Drug: Comparator: sitagliptin; A single dose of 50 mg sitagliptin tablet; Other Names: Januvia; Drug: Comparator: metformin 850 mg; A single dose of metformin 850 mg tablet; Other Names: Glucophage
Experimental: Treatment F; sitagliptin/metformin 50 mg/850 mg tablet	Drug: Comparator: FMI sitagliptin/metformin 50 mg/850 mg FDC tablet; A single dose of FMI sitagliptin/metformin 50 mg/850 mg FDC tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: August 18, 2009
• First Submitted That Met QC Criteria: August 18, 2009
• First Posted (Estimate): August 19, 2009

Study Record Updates

• Last Update Posted (Estimate): June 9, 2015
• Last Update Submitted That Met QC Criteria: June 8, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: 0431A-095; MK0431A-095; 2009_636