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

• ClinicalTrials.gov Identifier: NCT00511108
• Recruitment Status: Completed
• First Posted: August 3, 2007
• Results First Posted: March 5, 2010
• Last Update Posted: May 12, 2017
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 211 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Actual Study Start Date: July 11, 2007
• Actual Primary Completion Date: February 24, 2009
• Actual Study Completion Date: February 24, 2009

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Glucagon 3-hour Total Area Under the Curve (AUC) After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ]
   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.
2. Percent Change From Baseline in Index of Static Beta-cell Sensitivity to Glucose After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ]

   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 :

1. Change From Baseline in Glucose 5-hour Total AUC After 12 Weeks of Treatment [ Time Frame: Baseline and 12 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

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

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00511108
• Other Study ID Numbers: 0431-061; MK0431-061; 2007_530
• First Posted: August 3, 2007
• Results First Posted: March 5, 2010
• Last Update Posted: May 12, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

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 Phosphate; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action