Sitagliptin Metformin/PPARg Agonist Combination Therapy Add-on (0431-052)

• ClinicalTrials.gov Identifier: NCT00350779
• Recruitment Status: Completed
• First Posted: July 11, 2006
• Results First Posted: July 3, 2009
• Last Update Posted: May 12, 2017
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

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/peroxisome proliferator-activated receptor gamma (PPARg) agonist combination therapy.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: sitagliptin; Drug: Comparator: Placebo; Drug: rosiglitazone; Drug: metformin; Drug: glipizide	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 262 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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 (MK0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and a PPARg Agonist
• Actual Study Start Date: June 12, 2006
• Actual Primary Completion Date: September 25, 2007
• Actual Study Completion Date: June 11, 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Sitagliptin	Drug: sitagliptin; Sitagliptin 100mg tablet each day for 54 weeks. All subjects will be given placebo to sitagliptin for a 2 week period.; Other Name: Januvia; Drug: 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.; Other Name: Avandia; Drug: 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: 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.); Other Name: Glucotrol
Placebo Comparator: 2; Placebo	Drug: Comparator: Placebo; Placebo to sitagliptin 100mg tablet each day for 54 weeks.; Drug: 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.; Other Name: Avandia; Drug: 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: 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.); Other Name: Glucotrol

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in HbA1c (Hemoglobin A1C) at Week 18 [ Time Frame: Baseline and 18 Weeks ]
   HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.

Secondary Outcome Measures :

1. Change From Baseline in FPG (Fasting Plasma Glucose) at Week 18 [ Time Frame: Baseline and 18 Weeks ]
   Change from baseline at Week 18 is defined as Week 18 minus Week 0
2. Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 18 [ Time Frame: Baseline and Week 18 ]
   Change from baseline at Week 18 is defined as Week 18 minus Week 0
3. Change From Baseline in HbA1c (Hemoglobin A1C) at Week 54 [ Time Frame: Baseline and Week 54 ]
   HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
4. Change From Baseline in FPG (Fasting Plasma Glucose) at Week 54 [ Time Frame: Baseline and Week 54 ]
   Change from baseline at Week 54 is defined as Week 54 minus Week 0
5. Change From Baseline in 2-hour PMG (Post-meal Glucose) at Week 54 [ Time Frame: Baseline and Week 54 ]
   Change from baseline at Week 54 is defined as Week 54 minus Week 0.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 78 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme LLC

More Information

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

Dobs AS, Goldstein BJ, Aschner P, Horton ES, Umpierrez GE, Duran L, Hill JS, Chen Y, Golm GT, Langdon RB, Williams-Herman DE, Kaufman KD, Amatruda JM, Ferreira JC. Efficacy and safety of sitagliptin added to ongoing metformin and rosiglitazone combination therapy in a randomized placebo-controlled 54-week trial in patients with type 2 diabetes. J Diabetes. 2013 Mar;5(1):68-79. doi: 10.1111/j.1753-0407.2012.00223.x.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00350779
• Other Study ID Numbers: 0431-052; MK0431-052; 2006_507
• First Posted: July 11, 2006
• Results First Posted: July 3, 2009
• Last Update Posted: May 12, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Keywords provided by Merck Sharp & Dohme LLC:

Type 2 Diabetes Mellitus

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Sitagliptin Phosphate; Rosiglitazone; Glipizide; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action