Sitagliptin and Pioglitazone Mechanism of Action Study in Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00511108
First received: August 2, 2007
Last updated: April 20, 2010
Last verified: April 2010
  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 1

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:


Further study details as provided by Merck Sharp & Dohme Corp.:

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 Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Additional Information:
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 Sharp & Dohme Corp.:
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 April 16, 2014