Sitagliptin (MK-0431) vs. Placebo in Patients With Inadequate Glycemic Control on Metformin With Pioglitazone (MK-0431-128)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Phase III Randomized, Placebo-Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin (MK-0431) in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Metformin and Pioglitazone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00885352
• Other study ID #: 0431-128
• Secondary ID: 2009_577
• Status: Completed
• Phase: Phase 3
• First received: April 20, 2009
• Last updated: July 27, 2015
• Start date: April 2009
• Est. completion date: November 2010

Study information

• Verified date: July 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

This study will examine the safety and efficacy of the addition of sitagliptin (MK-0431) compared to placebo in patients with type 2 diabetes mellitus with inadequate glycemic control who are taking pioglitazone and metformin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

Inclusion Criteria:

• has type 2 diabetes and is at least 18 years of age and no older than 78 years of age

• is male or is a female who is unlikely to conceive children

• is on stable doses of a peroxisome proliferator-activated receptor gamma agonist and metformin OR metformin and a sulfonylurea agent

Exclusion Criteria:

• has type 1 diabetes

• has taken a dipeptidyl peptidase (DPP-4) inhibitor or a glucagon-like peptide-1 (GLP-1) analogue

• is on a weight loss program that is not in the maintenance phase or has started a weight loss medication within 8 weeks of screening

• has had surgery within 30 days of screening or has major surgery planned during the study

• is on or is likely to require treatment with corticosteroids for more than 2 weeks

• has a history of active liver disease, including hepatitis B or C, cirrhosis, or gallbladder disease

• is human immunodeficiency virus (HIV) positive

• has congestive heart failure, or has had new or worsening symptoms of coronary heart disease within 3 months prior to screening

• has had acute coronary syndrome, coronary artery intervention, or stroke within 3 months of screening

• has severe active peripheral vascular disease

• has a history of cancer or blood disorder

• is pregnant or breast feeding

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

Intervention

Drug:
• Sitagliptin
Sitagliptin 100 mg tablet orally once daily for 26 weeks.
• Comparator: Placebo
Placebo to sitagliptin 100 mg tablet orally once daily for 26 weeks.
• Pioglitazone
Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks.
• Metformin
Participants taking 1500 mg or more metformin oral tablet(s) and at least 30 mg pioglitazone or 4 mg rosiglitazone daily at screening will enter a 4-week dose-stable period followed by a 2-week single-blind placebo run-in, and a 26-week treatment period. Participants who are taking less than 1500 mg/day metformin at screening will be titrated to a stable dose of at least 1500 mg metformin once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with metformin will be up to 42 weeks.
• Glipizide
Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (A1C) at Week 26	Change from baseline reflects the Week 26 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.	Baseline and Week 26	No
Secondary	Change From Baseline in 2-Hour Post-Meal Glucose (PMG) at Week 26	Change from baseline reflects the Week 26 value minus the baseline value.	Baseline and Week 26	No
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	Change from baseline reflects the Week 26 value minus the baseline value.	Baseline and Week 26	No