Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on - Full Text View

Sponsored by:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00350779

Purpose

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/PPARg agonist combination therapy.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Comparator: sitagliptin Drug: Comparator: Placebo Drug: Comparator: rosiglitazone Drug: Comparator: metformin Drug: Comparator: glipizide	Phase III

MedlinePlus related topics: Diabetes

Drug Information available for: Glipizide Metformin Metformin hydrochloride Rosiglitazone Rosiglitazone Maleate Sitagliptin phosphate Sitagliptin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel 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 a PPARg Agonist

Further study details as provided by Merck:

Primary Outcome Measures:

HbA1c after 18 weeks, safety and tolerability. [ Time Frame: 18 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

2-hour PPG, C-peptide, insulin, and proinsulin following a standard meal challenge and FPG after 18 weeks; HbA1c after 54 weeks. [ Time Frame: 18 Weeks and 54 Weeks ] [ Designated as safety issue: No ]

Enrollment:	300
Study Start Date:	June 2006
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Sitagliptin	Drug: Comparator: sitagliptin Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period. Drug: Comparator: 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. Drug: Comparator: 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: Comparator: 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.)
2: Placebo Comparator Placebo	Drug: Comparator: Placebo Placebo to sitagliptin 100mg tablet each day for 54 weeks. Drug: Comparator: 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. Drug: Comparator: 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: Comparator: 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.)

Arms

Assigned Interventions

1: Experimental

Sitagliptin

Drug: Comparator: sitagliptin

Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.

Drug: Comparator: 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.

Drug: Comparator: 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: Comparator: 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.)

2: Placebo Comparator

Placebo

Drug: Comparator: Placebo

Placebo to sitagliptin 100mg tablet each day for 54 weeks.

Drug: Comparator: 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.

Drug: Comparator: 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: Comparator: 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.)

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00350779

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More 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

Responsible Party:	Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers:	2006_507, MK0431-052
Study First Received:	July 7, 2006
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00350779
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

Type 2 Diabetes Mellitus

Study placed in the following topic categories:

Glipizide
Metabolic Diseases
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases

Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Rosiglitazone
Sitagliptin

Additional relevant MeSH terms:

Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009