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

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

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.

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

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.

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.

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.)

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.

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

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

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.