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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: Comparator: sitagliptin phosphate; Drug: Comparator: placebo to pioglitazone; Drug: Comparator: pioglitazone; Drug: Comparator: placebo to sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Alba M, Ahren 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. 2013 Dec;15(12):1101-10. doi: 10.1111/dom.12145. Epub 2013 Jul 19.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2007
• Primary Completion (Actual): February 24, 2009
• Study Completion (Actual): February 24, 2009

Study Registration Dates

• First Submitted: August 2, 2007
• First Submitted That Met QC Criteria: August 2, 2007
• First Posted (Estimate): August 3, 2007

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitus (T2DM)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Pioglitazone; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-061; MK0431-061; 2007_530

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD 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