Sitagliptin (MK-0431) vs. Placebo in Patients With Inadequate Glycemic Control on Metformin With Pioglitazone (MK-0431-128)(COMPLETED) - Full Text View

Purpose

This study will examine the safety and efficacy of the addition of sitagliptin (MK-0431) 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: Sitagliptin Drug: Comparator: Placebo Drug: Pioglitazone Drug: Metformin Drug: Glipizide	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK-0431) 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 Diabetes Type 2

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

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Change From Baseline in Hemoglobin A1c (A1C) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
Change from baseline reflects the Week 26 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.

Secondary Outcome Measures:

Change From Baseline in 2-Hour Post-Meal Glucose (PMG) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
Change from baseline reflects the Week 26 value minus the baseline value.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
Change from baseline reflects the Week 26 value minus the baseline value.

Enrollment:	313
Study Start Date:	April 2009
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sitagliptin Sitagliptin 100 mg tablet orally once daily for 26 weeks.	Drug: Sitagliptin Sitagliptin 100 mg tablet orally once daily for 26 weeks. Other Names: Januvia MK-0431 Drug: Pioglitazone Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants 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 pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks. Other Name: Actos Drug: Metformin Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks. Other Name: Glucophage Drug: Glipizide Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country. Other Name: Glucotrol
Placebo Comparator: Placebo Placebo to sitagliptin orally once daily for 26 weeks.	Drug: Comparator: Placebo Placebo to sitagliptin 100 mg tablet orally once daily for 26 weeks. Drug: Pioglitazone Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants 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 pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks. Other Name: Actos Drug: Metformin Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks. Other Name: Glucophage Drug: Glipizide Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country. Other Name: Glucotrol

Arms

Assigned Interventions

Experimental: Sitagliptin

Sitagliptin 100 mg tablet orally once daily for 26 weeks.

Drug: Sitagliptin

Sitagliptin 100 mg tablet orally once daily for 26 weeks.

Other Names:

Januvia
MK-0431

Drug: Pioglitazone

Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants 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 pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks.

Other Name: Actos

Drug: Metformin

Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks.

Other Name: Glucophage

Drug: Glipizide

Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country.

Other Name: Glucotrol

Placebo Comparator: Placebo

Placebo to sitagliptin orally once daily for 26 weeks.

Drug: Comparator: Placebo

Placebo to sitagliptin 100 mg tablet orally once daily for 26 weeks.

Drug: Pioglitazone

Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants 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 pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks.

Other Name: Actos

Drug: Metformin

Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks.

Other Name: Glucophage

Drug: Glipizide

Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country.

Other Name: Glucotrol

Eligibility

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

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

has type 1 diabetes
has taken a dipeptidyl peptidase (DPP-4) inhibitor or a glucagon-like peptide-1 (GLP-1) analogue
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
has had surgery within 30 days of screening or has major surgery planned during the study
is on or is likely to require treatment with corticosteroids for more than 2 weeks
has a history of active liver disease, including hepatitis B or C, cirrhosis, or gallbladder disease
is human immunodeficiency virus (HIV) positive
has congestive heart failure, or has had new or worsening symptoms of coronary heart disease within 3 months prior to screening
has had acute coronary syndrome, coronary artery intervention, or stroke within 3 months of screening
has severe active peripheral vascular disease
has a history of cancer or blood disorder
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

No publications provided by Merck

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fonseca V, Staels B, Morgan JD 2nd, Shentu Y, Golm GT, Johnson-Levonas AO, Kaufman KD, Goldstein BJ, Steinberg H. Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes. J Diabetes Complications. 2013 Mar-Apr;27(2):177-83. doi: 10.1016/j.jdiacomp.2012.09.007. Epub 2012 Oct 30.

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00885352 History of Changes
Other Study ID Numbers:	MK-0431-128, 2009_577
Study First Received:	April 20, 2009
Results First Received:	November 4, 2011
Last Updated:	December 27, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Sitagliptin
Glipizide

Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2013