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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00885352
First received: April 20, 2009
Last updated: August 1, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Comparator: Placebo
Drug: Pioglitazone
Drug: Metformin
Drug: Glipizide
Phase 3

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 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in Hemoglobin A1c (A1C) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 26 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.


Secondary Outcome Measures:
  • Change From Baseline in 2-Hour Post-Meal Glucose (PMG) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 26 value minus the baseline value.

  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 26 value minus the baseline value.


Enrollment: 313
Study Start Date: April 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Sitagliptin 100 mg tablet orally once daily for 26 weeks.
Drug: Sitagliptin
Sitagliptin 100 mg tablet orally once daily for 26 weeks.
Other Names:
  • Januvia
  • MK-0431
Drug: 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.
Other Name: Actos
Drug: 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.
Other Name: Glucophage
Drug: 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.
Other Name: Glucotrol
Placebo Comparator: Placebo
Placebo to sitagliptin orally once daily for 26 weeks.
Drug: Comparator: Placebo
Placebo to sitagliptin 100 mg tablet orally once daily for 26 weeks.
Drug: 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.
Other Name: Actos
Drug: 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.
Other Name: Glucophage
Drug: 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.
Other Name: Glucotrol

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00885352

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

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00885352     History of Changes
Other Study ID Numbers: 0431-128, 2009_577
Study First Received: April 20, 2009
Results First Received: November 4, 2011
Last Updated: August 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glipizide
Metformin
Pioglitazone
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014