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

NCT00885352 | Completed Phase 3 Results

• 2 other identifiers: 0431-1282009_577
• Study Type: interventional
• Target: 313
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Change From Baseline in 2-Hour Post-Meal Glucose (PMG) at Week 26

  Baseline and Week 26

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

  Baseline and Week 26

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Sitagliptin 100 mg tablet orally once daily for 26 weeks.

Drug: Sitagliptin; Drug: Pioglitazone; Drug: Metformin; Drug: Glipizide

Placebo

PLACEBO COMPARATOR

Placebo to sitagliptin orally once daily for 26 weeks.

Drug: Comparator: Placebo; Drug: Pioglitazone; Drug: Metformin; Drug: Glipizide

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg tablet orally once daily for 26 weeks.

Also known as: Januvia, MK-0431

Sitagliptin

Comparator: Placebo DRUG

Placebo to sitagliptin 100 mg tablet orally once daily for 26 weeks.

Placebo

Pioglitazone DRUG

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.

Also known as: Actos

Placebo; Sitagliptin

Metformin DRUG

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.

Also known as: Glucophage

Placebo; Sitagliptin

Glipizide DRUG

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.

Also known as: Glucotrol

Placebo; Sitagliptin

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Fonseca V, Staels B, Morgan JD 2nd, Shentu Y, Golm GT, Johnson-Levonas AO, Kaufman KD, Goldstein BJ, Steinberg H. Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes. J Diabetes Complications. 2013 Mar-Apr;27(2):177-83. doi: 10.1016/j.jdiacomp.2012.09.007. Epub 2012 Oct 30.

  PMID: 23116881 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Pioglitazone; Metformin; Glipizide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Biguanides; Guanidines; Amidines; Sulfonylurea Compounds; Sulfones

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2009
• First Posted: April 21, 2009
• Study Start: April 15, 2009
• Primary Completion: November 10, 2010
• Study Completion: November 10, 2010
• Last Updated: May 23, 2017
• Results First Posted: February 1, 2012

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share