Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052)

A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and a PPARg Agonist

A clinical study to determine the safety and efficacy of sitagliptin in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin/peroxisome proliferator-activated receptor gamma (PPARg) agonist combination therapy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: sitagliptin; Drug: rosiglitazone; Drug: metformin; Drug: glipizide; Drug: Comparator: Placebo

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient has type 2 diabetes mellitus
• Patient is inadequately controlled while taking two oral antidiabetic medications

Exclusion Criteria:

• Patient has a history of type 1 diabetes mellitus or history of ketoacidosis
• Patient required insulin therapy within the prior 3 months
• Patient has been taking Byetta (R) (exenatide) within the prior 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: rosiglitazone; Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.; Other Names: Avandia; Drug: metformin; Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.; Drug: glipizide; Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.); Other Names: Glucotrol; Drug: Comparator: Placebo; Placebo to sitagliptin 100mg tablet each day for 54 weeks.
Experimental: 1; Sitagliptin	Drug: sitagliptin; Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.; Other Names: Januvia; Drug: rosiglitazone; Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.; Other Names: Avandia; Drug: metformin; Subjects taking 1500mg or greater metformin at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 1500mg/day or no metformin at screening will be titrated to a stable dose of at least 1500mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks.; Drug: glipizide; Subjects not meeting specific glycemic controls during the 54-week treatment period will use glipizide as rescue therapy. Glipizide will be titrated in 5mg doses up to a maximum 40mg each day. (In Canada, the rescue therapy will be a sulfonylurea agent marketed in that country.); Other Names: Glucotrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18	HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.	Baseline and 18 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18	Change from baseline at Week 18 is defined as Week 18 minus Week 0	Baseline and 18 Weeks
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18	Change from baseline at Week 18 is defined as Week 18 minus Week 0	Baseline and Week 18
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54	HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.	Baseline and Week 54
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54	Change from baseline at Week 54 is defined as Week 54 minus Week 0	Baseline and Week 54
Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54	Change from baseline at Week 54 is defined as Week 54 minus Week 0.	Baseline and Week 54

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Dobs AS, Goldstein BJ, Aschner P, Horton ES, Umpierrez GE, Duran L, Hill JS, Chen Y, Golm GT, Langdon RB, Williams-Herman DE, Kaufman KD, Amatruda JM, Ferreira JC. Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes. J Diabetes. 2013 Mar;5(1):68-79. doi: 10.1111/j.1753-0407.2012.00223.x.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2006
• Primary Completion (Actual): September 25, 2007
• Study Completion (Actual): June 11, 2008

Study Registration Dates

• First Submitted: July 7, 2006
• First Submitted That Met QC Criteria: July 7, 2006
• First Posted (Estimate): July 11, 2006

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: April 6, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitus
• 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; Rosiglitazone; Sitagliptin Phosphate; Glipizide
• Other Study ID Numbers: 0431-052; MK0431-052; 2006_507

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No