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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1. Sit + Met500 / SitMet500 FDC / SitMet850 FDC / Sit + Met850; 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; 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.; Drug: sitagliptin/metformin 50 mg/500 mg tablet; 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.; Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin; 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.; Drug: sitagliptin/metformin 50 mg/850 mg tablet; 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.
EXPERIMENTAL: 2. SitMet500 FDC / Sit + Met850 / Sit + Met500 / SitMet850 FDC; 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; 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.; Drug: sitagliptin/metformin 50 mg/500 mg tablet; 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.; Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin; 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.; Drug: sitagliptin/metformin 50 mg/850 mg tablet; 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.
EXPERIMENTAL: 3. Sit + Met850 / SitMet850 FDC / SitMet500 FDC / Sit + Met500; 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; 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.; Drug: sitagliptin/metformin 50 mg/500 mg tablet; 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.; Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin; 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.; Drug: sitagliptin/metformin 50 mg/850 mg tablet; 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.
EXPERIMENTAL: 4. SitMet850 FDC / Sit + Met500 / Sit + Met850 / SitMet500 FDC; 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; 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.; Drug: sitagliptin/metformin 50 mg/500 mg tablet; 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.; Drug: Co-administration of 50 mg sitagliptin and 850 mg metformin; 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.; Drug: sitagliptin/metformin 50 mg/850 mg tablet; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: March 19, 2010
• First Submitted That Met QC Criteria: March 24, 2010
• First Posted (ESTIMATE): March 26, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 28, 2015
• Last Update Submitted That Met QC Criteria: July 17, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Type 2 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; 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-122; 2010_518