Monotherapy Study in Patients With Type 2 Diabetes Mellitus (0431-021)

A Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of MK0431 Monotherapy in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

The purpose of this clinical study is to determine the safety and efficacy of an investigational drug in patients with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Sitagliptin (MK0431); Drug: Metformin - Rescue; Drug: Sitagliptin; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 741
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with type 2 diabetes mellitus
• Patient is not pregnant or breastfeeding
• Male or female patient unlikely to conceive
• Patient not on an antihyperglycemic drug

Exclusion Criteria:

• Patient has history of type 1 diabetes mellitus
• Patient has history of ketoacidosis
• Patient requires insulin within 8 weeks prior to start of study
• Patient on weight loss program and is not in maintenance phase
• Patient taking weight loss medication within 8 weeks prior to start of study
• Patient on or likely to require = 14 days or repeated courses of corticosteroids
• Patient taking immunosuppressive/immunomodulating medication
• Patient taking digoxin or other cardiac medication
• Patient has undergone surgical general anesthesia within 30 days prior to start of study
• Patient taking investigational drug within 8 weeks prior to start of study
• Patient is diagnosed with liver disease
• Patient has chronic myopathy, progressive neurological/neuromuscular disorder
• Patient has with severe cardiac conditions within the last 6 months
• Patient is Human immunodeficiency virus (HIV) positive
• Patient has hematological disorder
• Patient has history of malignancy
• Patient has history of alcohol or drug abuse within the past 3 years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sitagliptin 100 mg/100 mg; Phase A and B: Oral tablets of sitagliptin 100 mg Once a Day (q.d )	Drug: Sitagliptin (MK0431); Phase A: Sitagliptin 100 mg once a day for 24 weeks. Phase B: Sitagliptin 100 mg once a day for 80 weeks.; Other Names: Januvia; MK0431; Drug: Metformin - Rescue; Phase A: Patients not meeting specific glycemic goals will receive open-label metformin as 500 mg, 850 mg, and 1000 mg oral tablets titrated at the discretion of the investigator. Phase B: These patients will not initiate Phase B double-blind medication.; Other Names: Glucophage; Glucophage XR; Metformin; Glumetza; Fortamet; Riomet
Active Comparator: Sitagliptin 200 mg/200 mg; Phase A and B: Oral tablets of sitagliptin 200 mg q.d	Drug: Metformin - Rescue; Phase A: Patients not meeting specific glycemic goals will receive open-label metformin as 500 mg, 850 mg, and 1000 mg oral tablets titrated at the discretion of the investigator. Phase B: These patients will not initiate Phase B double-blind medication.; Other Names: Glucophage; Glucophage XR; Metformin; Glumetza; Fortamet; Riomet; Drug: Sitagliptin; Phase A: Sitagliptin 200 mg once a day for 24 weeks. Phase B: Sitagliptin 200 mg once a day for 80 weeks.; Other Names: Januvia; MK0431
Placebo Comparator: Placebo/Sitagliptin 100 mg; Phase A: Oral tablets of placebo matching sitagliptin 100 mg q.d. Phase B: Oral tablets of sitagliptin 100 mg q.d.	Drug: Metformin - Rescue; Phase A: Patients not meeting specific glycemic goals will receive open-label metformin as 500 mg, 850 mg, and 1000 mg oral tablets titrated at the discretion of the investigator. Phase B: These patients will not initiate Phase B double-blind medication.; Other Names: Glucophage; Glucophage XR; Metformin; Glumetza; Fortamet; Riomet; Drug: Placebo; Phase A: Placebo matching Sitagliptin 100 mg once a day for 24 weeks. Phase B: Sitagliptin 100 mg once a day for 80 weeks.; Drug: Placebo; Phase A: Placebo matching Sitagliptin 200 mg once a day for 24 weeks. Phase B: Sitagliptin 200 mg once a day for 80 weeks.
Placebo Comparator: Placebo/Sitagliptin 200 mg; Phase A: Oral tablets of placebo matching sitagliptin 200 mg q.d. Phase B: Oral tablets of sitagliptin 200 mg q.d.	Drug: Metformin - Rescue; Phase A: Patients not meeting specific glycemic goals will receive open-label metformin as 500 mg, 850 mg, and 1000 mg oral tablets titrated at the discretion of the investigator. Phase B: These patients will not initiate Phase B double-blind medication.; Other Names: Glucophage; Glucophage XR; Metformin; Glumetza; Fortamet; Riomet; Drug: Placebo; Phase A: Placebo matching Sitagliptin 100 mg once a day for 24 weeks. Phase B: Sitagliptin 100 mg once a day for 80 weeks.; Drug: Placebo; Phase A: Placebo matching Sitagliptin 200 mg once a day for 24 weeks. Phase B: Sitagliptin 200 mg once a day for 80 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in A1C at Week 24	A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.	Weeks 0-24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in FPG at Week 24	Change from baseline at Week 24 is defined as Week 24 FPG minus Week 0 FPG.	Weeks 0-24
Change From Baseline in 2-hour Post-meal Glucose (2-hr PMG) at Week 24	Change from baseline at Week 24 is defined as Week 24 2-hr PMG minus Week 0 2-hr PMG.	Weeks 0-24
Change From Baseline in A1C at Week 104	A1C is measured as a percent. Thus, this change from baseline reflects the Week 104 A1C percent minus the Week 0 A1C percent.	Weeks 0-104
Change From Baseline in FPG at Week 104	Change from baseline at Week 104 is defined as Week 104 FPG minus Week 0 FPG.	Weeks 0-104
Change From Baseline in 2-hr PMG at Week 104	Change from baseline at Week 104 is defined as Week 104 2-hr PMG minus Week 0 2-hr PMG.	Weeks 0-104

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006 Dec;29(12):2632-7. doi: 10.2337/dc06-0703.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): July 1, 2005
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: July 9, 2004
• First Submitted That Met QC Criteria: July 12, 2004
• First Posted (Estimate): July 13, 2004

Study Record Updates

• Last Update Posted (Estimate): July 3, 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: 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: 0431-021; Formally-C0604MT2D; MK0431-021; 2006_413