Sitagliptin (MK0431) vs. Placebo in Patients With Inadequate Glycemic Control on Metformin With Pioglitazone - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00885352

Purpose

This study will examine the safety and efficacy of the addition of sitagliptin (MK0431) compared to placebo in patients with type 2 diabetes mellitus with inadequate glycemic control who are taking pioglitazone and metformin.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: MK0431C Drug: Comparator: placebo Drug: Comparator: pioglitazone Drug: Comparator: metformin Drug: Comparator: glipizide	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	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 Pioglitazone

Resource links provided by NLM:

MedlinePlus related topics: Diabetes

Drug Information available for: Glipizide Pioglitazone Pioglitazone hydrochloride Sitagliptin Sitagliptin phosphate Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Change from Baseline in HbA1c (Hemoglobin A1c) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in 2-Hour PMG (Post Meal Glucose) [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]
Change from baseline in FPG (Fasting Plasma Glucose) at Week 26 [ Time Frame: 26 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	266
Study Start Date:	April 2009
Estimated Study Completion Date:	November 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Sitagliptin	Drug: MK0431C [Intervention Name: Sitagliptin] Sitagliptin (MK0431) 100 mg tablet once daily for 26 weeks. All patients will be given placebo to sitagliptin for a 2 week period. Drug: Comparator: pioglitazone Patients taking 30 mg or more pioglitazone (and at least 1500 mg metformin) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with pioglitazone will be up to 42 weeks. Drug: Comparator: metformin Patients taking 1500 mg or more metformin (and at least 30 mg pioglitazone) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 1500 mg/day or no metformin at screening will be titrated to a stable dose of at least 1500 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with metformin will be up to 42 weeks. Drug: Comparator: glipizide Patients not meeting specific glycemic controls during the 26-week treatment period will use glipizide as rescue therapy. In countries where glipizide is not available, another sulfonylurea marketed in that country will be used.
2: Placebo Comparator Placebo	Drug: Comparator: placebo Placebo to sitagliptin (MK0431) 100 mg tablets once daily for 26 weeks. Drug: Comparator: pioglitazone Patients taking 30 mg or more pioglitazone (and at least 1500 mg metformin) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with pioglitazone will be up to 42 weeks. Drug: Comparator: metformin Patients taking 1500 mg or more metformin (and at least 30 mg pioglitazone) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 1500 mg/day or no metformin at screening will be titrated to a stable dose of at least 1500 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with metformin will be up to 42 weeks. Drug: Comparator: glipizide Patients not meeting specific glycemic controls during the 26-week treatment period will use glipizide as rescue therapy. In countries where glipizide is not available, another sulfonylurea marketed in that country will be used.

Arms

Assigned Interventions

1: Experimental

Sitagliptin

Drug: MK0431C

[Intervention Name: Sitagliptin] Sitagliptin (MK0431) 100 mg tablet once daily for 26 weeks. All patients will be given placebo to sitagliptin for a 2 week period.

Drug: Comparator: pioglitazone

Patients taking 30 mg or more pioglitazone (and at least 1500 mg metformin) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with pioglitazone will be up to 42 weeks.

Drug: Comparator: metformin

Patients taking 1500 mg or more metformin (and at least 30 mg pioglitazone) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 1500 mg/day or no metformin at screening will be titrated to a stable dose of at least 1500 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with metformin will be up to 42 weeks.

Drug: Comparator: glipizide

Patients not meeting specific glycemic controls during the 26-week treatment period will use glipizide as rescue therapy. In countries where glipizide is not available, another sulfonylurea marketed in that country will be used.

2: Placebo Comparator

Placebo

Drug: Comparator: placebo

Placebo to sitagliptin (MK0431) 100 mg tablets once daily for 26 weeks.

Drug: Comparator: pioglitazone

Patients taking 30 mg or more pioglitazone (and at least 1500 mg metformin) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with pioglitazone will be up to 42 weeks.

Drug: Comparator: metformin

Patients taking 1500 mg or more metformin (and at least 30 mg pioglitazone) at screening will enter a 4 week dose-stable period followed by a 26 week treatment period. Patients who are taking less than 1500 mg/day or no metformin at screening will be titrated to a stable dose of at least 1500 mg once daily over a maximum of 4 weeks followed by a stable-dose period of 10 weeks then a 26 week treatment period. Total treatment with metformin will be up to 42 weeks.

Drug: Comparator: glipizide

Patients not meeting specific glycemic controls during the 26-week treatment period will use glipizide as rescue therapy. In countries where glipizide is not available, another sulfonylurea marketed in that country will be used.

Eligibility

Ages Eligible for Study:	18 Years to 78 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient has type 2 diabetes and is at least 18 years of age and no older than 78 years of age
Patient is male or is a female who is unlikely to conceive children
Patient is on stable doses of a PPARg agonist and metformin OR metformin and a sulfonylurea agent

Exclusion Criteria:

Patient has Type 1 diabetes
Patient has taken a DPP-4 inhibitor or a GLP-1 analogue
Patient is on a weight loss program that is not in the maintenance phase or has started a weight loss medication within 8 weeks of screening
Patient has had surgery within 30 days of screening or has major surgery planned during the study
Patient is on or is likely to require treatment with corticosteroids for more than 2 weeks
Patient has a history of active liver disease, including hepatitis B or C, cirrhosis, or gallbladder disease
Patient is HIV positive
Patient has congestive heart failure, or has had new or worsening symptoms of coronary heart disease within 3 months prior to screening
Patient has had acute coronary syndrome, coronary artery intervention, or stroke within 3 months of screening
Patient has severe active peripheral vascular disease
Patient has a history of cancer or blood disorder
Patient is pregnant or breast feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00885352

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Additional Information:

MedWatch - FDA maintained medical product safety Information This link exits the ClinicalTrials.gov site

PhRMA Clinical Study Results Database - web-based repository for clinical study results This link exits the ClinicalTrials.gov site

Merck: Patient & Caregiver U.S. Product Web Site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers:	2009_577, MK0431-128
Study First Received:	April 20, 2009
Last Updated:	January 27, 2010
ClinicalTrials.gov Identifier:	NCT00885352 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Metabolic Diseases
Glipizide
Molecular Mechanisms of Pharmacological Action
Pioglitazone
Metformin
Physiological Effects of Drugs
Diabetes Mellitus
Endocrine System Diseases

Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010