Pioglitazone Add-on Study in Patients With Type 2 Diabetes Mellitus

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

The purpose of this 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: Comparator: Sitagliptin; Drug: Comparator: Pioglitazone; Drug: Metformin; Drug: Comparator: Placebo

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient has type 2 diabetes mellitus (T2DM)
• Patient is 18 years of age (or older)
• Patient is not pregnant or breast-feeding and does not plan to become pregnant for the duration of the study and poststudy follow-up period

Exclusion Criteria:

• Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis
• Patient required insulin within the prior 8 weeks
• Patient is on a weight loss program and is not in the maintenance phase
• Patient started on a weight loss medication (e.g., orlistat or sibutramine) within the prior 8 weeks
• Patient is on or likely to require treatment with treatment with immunosuppressive agents (e.g., cyclosporin, methotrexate)
• Patient has cirrhosis, active liver disease (other than fatty liver) or symptomatic gallbladder disease
• Patient has chronic myopathy, or a progressive neurological or neuromuscular disorder (e.g., multiple sclerosis or polymyositis)
• Patient has any of the following disorders within the past 6 months:

Acute coronary syndrome (e.g., MI or unstable angina), Coronary artery intervention, Stroke or transient ischemic neurological disorder.

• Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months
• Patient has severe peripheral vascular disease
• Patient has congestive heart failure
• Patient is HIV positive
• Patient has a clinically important hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
• Patient has a history of neoplastic disease
• Patient has a history of alcohol or drug abuse within the past 3 years
• Patient has viral hepatitis (hepatitis B or C)

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: Placebo	Drug: Comparator: Pioglitazone; Pioglitazone 30 mg or 45 mg once daily, Visit 2 through Visit 8; Other Names: ACTOS; Drug: Metformin; Metformin rescue for patients meeting pre-specified glycemic criteria. Metformin 500 mg,once daily, Visit 4 through Visit 8; Drug: Comparator: Placebo; Placebo (to match Sitagliptin 100 mg) once daily, from Visit 4 through Visit 8. Day 1 through Week 24
Active Comparator: Sitagliptin 100 mg	Drug: Comparator: Sitagliptin; Sitagliptin 100 mg once daily, from Visit 4 through Visit 8. Day 1 through week 24; Other Names: Januvia; Drug: Comparator: Pioglitazone; Pioglitazone 30 mg or 45 mg once daily, Visit 2 through Visit 8; Other Names: ACTOS; Drug: Metformin; Metformin rescue for patients meeting pre-specified glycemic criteria. Metformin 500 mg,once daily, Visit 4 through Visit 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24	HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.	Baseline and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24	Change from baseline at Week 24 is defined as Week 24 minus Week 0.	Baseline and week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P; Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006 Oct;28(10):1556-68. doi: 10.1016/j.clinthera.2006.10.007.

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: July 2, 2004
• First Submitted That Met QC Criteria: July 2, 2004
• First Posted (Estimate): July 5, 2004

Study Record Updates

• Last Update Posted (Estimate): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

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; Pioglitazone; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-019; Formally-A0604T2DPT; 2006_410