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

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: sitagliptin phosphate (+) metformin hydrochloride; Drug: Comparator: FMI sitagliptin/metformin 50 mg/1000 mg FDC tablet; Drug: Comparator: metformin 500 mg; Drug: Comparator: sitagliptin; Drug: Comparator: FMI sitagliptin/metformin 50 mg/500 mg FDC tablet; Drug: Comparator: metformin 1000 mg

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• 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
• 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

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
ACTIVE_COMPARATOR: Treatment A; Individual Tablets of 50 mg sitagliptin and 500 mg metformin	Drug: sitagliptin phosphate (+) metformin hydrochloride; place holder - do not post; Drug: Comparator: metformin 500 mg; A single dose of metformin 500 mg tablets; Other Names: Apotex; Drug: Comparator: sitagliptin; A single 50 mg tablet of sitagliptin
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; Individual Tablets of 50 mg sitagliptin and 1000 mg metformin	Drug: Comparator: sitagliptin; A single 50 mg tablet of sitagliptin; Drug: Comparator: metformin 1000 mg; A single dose of metformin 1000 mg tablets; Other Names: Apotex
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Migoya EM, Miller JL, Gutierrez M, Zheng W, Johnson-Levonas AO, Liu Q, Matthews CZ, Wagner JA, Gottesdiener KM. Bioequivalence of sitagliptin/metformin fixed-dose combination tablets and concomitant administration of sitagliptin and metformin in healthy adult subjects: a randomized, open-label, crossover study. Clin Drug Investig. 2010;30(12):855-66. doi: 10.1007/BF03256914.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2005
• Primary Completion (ACTUAL): December 1, 2005
• Study Completion (ACTUAL): January 1, 2006

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 (ACTUAL): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

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-048; MK0431A-048; 2009_635