Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00511108

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus (T2DM)	Drug: Comparator: sitagliptin phosphate Drug: Comparator: pioglitazone Drug: Comparator: placebo to pioglitazone Drug: Comparator: placebo to sitagliptin	Phase I

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 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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Pioglitazone Pioglitazone hydrochloride Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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.
Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
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.

Enrollment:	211
Study Start Date:	July 2007
Study Completion Date:	February 2009
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Arm 1: drug	Drug: Comparator: sitagliptin phosphate sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily. Drug: Comparator: placebo to pioglitazone pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
Active Comparator: 2 Arm 2: active comparator	Drug: Comparator: pioglitazone pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily. Drug: Comparator: placebo to sitagliptin sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
Experimental: 3 Arm 3: drug + active comparator	Drug: Comparator: sitagliptin phosphate sitagliptin phosphate 100 mg as oral tablets. Each patient will be administered 1 tablet once daily. Drug: Comparator: pioglitazone pioglitazone 30 mg will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.
Placebo Comparator: 4 Arm 4: placebo comparator	Drug: Comparator: placebo to pioglitazone pioglitazone 30 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily. Drug: Comparator: placebo to sitagliptin sitagliptin phosphate 100 mg placebos will be supplied as oral tablets. Each patient will be administered 1 tablet once daily.

Eligibility

Ages Eligible for Study:	30 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511108

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

Additional Information:

MedWatch - FDA maintained medical product safety Information This link exits the ClinicalTrials.gov site

Merck: Patient & Caregiver U.S. Product Web Site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00511108 History of Changes
Other Study ID Numbers:	2007_530, MK0431-061
Study First Received:	August 2, 2007
Results First Received:	January 8, 2010
Last Updated:	April 20, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Merck:

Type 2 Diabetes Mellitus (T2DM)

Additional relevant MeSH terms:

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

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 February 09, 2012