Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus (0431-061)

Type 2 Diabetes Mellitus (T2DM) Clinical Trial

Official title:

A Phase I Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Study the Safety, Efficacy, and Mechanism of Action of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Diet and Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00511108
• Other study ID #: 0431-061
• Secondary ID: MK0431-0612007_5
• Status: Completed
• Phase: Phase 1
• First received: August 2, 2007
• Last updated: June 8, 2015
• Start date: July 2007
• Est. completion date: February 2009

Study information

• Verified date: June 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

A clinical study to determine the safety, efficacy and mechanism of action of sitagliptin alone and in combination with pioglitazone, in patients with type 2 diabetes mellitus who have inadequate glycemic (blood sugar) control.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patient has type 2 diabetes mellitus

• Male

• Female that is highly unlikely to become pregnant

• Patient is not on an antihyperglycemic agent (AHA) (hemoglobin A1c [A1C] 7-10%) or on oral single AHA or low-dose combination therapy (A1C 6.5-9.0%)

Exclusion Criteria:

• Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis

• Patient has required insulin therapy within the past 12 weeks

• Patient is on or has been taking a Peroxisome Proliferator-Activated Receptor-gamma (PPAR -gamma) agent (i.e. Thiazolidinediones [TZDs]) within the prior 12 weeks of the screening visit.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus (T2DM)

Intervention

Drug:
• Comparator: sitagliptin phosphate
sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily.
• Comparator: pioglitazone
pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
• Comparator: placebo to pioglitazone
pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
• Comparator: placebo to sitagliptin
sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Alba M, Ahrén B, Inzucchi SE, Guan Y, Mallick M, Xu L, O'Neill EA, Williams-Herman DE, Kaufman KD, Goldstein BJ. Sitagliptin and pioglitazone provide complementary effects on postprandial glucose and pancreatic islet cell function. Diabetes Obes Metab. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment	Glucagon concentration was measured at 9 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, and 180 minutes. Total AUC was calculated over 3 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.	Baseline and 12 weeks	No
Primary	Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment	Static sensitivity is a measure of the effect of glucose on beta cell secretion and is the ratio between the insulin secretion rate and glucose concentration above the threshold level at steady state.; Percent change from baseline was calculated as the difference between index of static sensitivities at Week 12 and at baseline with respect to the index of static sensitivity at baseline times 100.	Baseline and 12 weeks	No
Secondary	Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment	Glucose concentration was measured at 11 points during an Meal Tolerance Test (MTT), at times -10, 0, 10, 20, 30, 60, 90, 120, 180, 240, 300 minutes. Total AUC was calculated over 5 hours including all sample points starting from 0 minutes using the trapezoid method. The change from baseline reflects Week 12 total AUC minus the Week 0 total AUC.	Baseline and 12 weeks	No

External Links

•   MedWatch - FDA maintained medical product safety Information
•   Merck: Patient & Caregiver U.S. Product Web Site