A Study to Evaluate the Safety and Efficacy of Sitagliptin 100 mg in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control (MK-0431-229)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01076075
First received: February 24, 2010
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

This study will evaluate whether the addition of Sitagliptin treatment provides a greater decrease in A1C levels compared to placebo in participants with inadequate glycemic control on sulfonylurea and metformin combination therapy.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin phosphate
Drug: Comparator: placebo to pioglitazone
Drug: Comparator: placebo to Sitagliptin
Drug: Comparator: pioglitazone
Drug: Glimepiride or gliclazide
Drug: Metformin
Drug: Pioglitazone rescue therapy
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, Clinical Trial to Evaluate the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on a Sulfonylurea in Combination With Metformin

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in Hemoglobin A1C (%) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 24 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.

  • Number of Participants With One or More Adverse Events (AEs) - Week 0 to Week 54 [ Time Frame: Week 0 to Week 54 ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Drug Due to An Adverse Event [ Time Frame: Week 0 to Week 54 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change From Baseline in 2-hour Post-Meal Glucose at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 24 value minus the baseline value. Two-hour post-meal glucose was measured following a standard meal.

  • Change From Baseline in Fasting Plasma Glucose at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Change from baseline reflects the Week 24 value minus the baseline value.


Enrollment: 427
Study Start Date: June 2010
Study Completion Date: January 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: placebo/pioglitazone
Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): placebo to Sitagliptin 100 mg + pioglitazone 30 mg
Drug: Comparator: placebo to Sitagliptin
Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): placebo to Sitagliptin once a day for 30 weeks
Drug: Comparator: pioglitazone
Phase B (Weeks 24-54): pioglitazone 30 mg once a day for 30 weeks
Other Name: Actos;
Drug: Glimepiride or gliclazide
Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of glimepiride or gliclazide; Phase B (Weeks 24-54): stable dose, as prescribed by investigator, of glimepiride or gliclazide
Drug: Metformin

Phase A (Weeks 0-24): stable dose, as prescribed

by investigator, of metformin; Phase B (Weeks 24-

54): stable dose, as prescribed by investigator, of

metformin

Drug: Pioglitazone rescue therapy
Phase A (Weeks 0-24): participants not meeting specific glycemic goals will receive pioglitazone (open label) at a dose determined by the investigator. These participants will not initiate Phase B (Weeks 24-54) double blind pioglitazone.
Other Name: Actos
Experimental: Sitagliptin
Phase A (Weeks 0-24): Sitagliptin 100 mg; Phase B (Weeks 24-54): Sitagliptin 100 mg + placebo to pioglitazone
Drug: Sitagliptin phosphate
Phase A (Weeks 0-24): Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): Sitagliptin 100 mg once a day for 30 weeks
Other Name: Januvia
Drug: Comparator: placebo to pioglitazone
Phase B (Weeks 24-54): placebo to pioglitazone 30 mg once a day for 30 weeks
Drug: Glimepiride or gliclazide
Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of glimepiride or gliclazide; Phase B (Weeks 24-54): stable dose, as prescribed by investigator, of glimepiride or gliclazide
Drug: Metformin

Phase A (Weeks 0-24): stable dose, as prescribed

by investigator, of metformin; Phase B (Weeks 24-

54): stable dose, as prescribed by investigator, of

metformin

Drug: Pioglitazone rescue therapy
Phase A (Weeks 0-24): participants not meeting specific glycemic goals will receive pioglitazone (open label) at a dose determined by the investigator. These participants will not initiate Phase B (Weeks 24-54) double blind pioglitazone.
Other Name: Actos

  Eligibility

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

Inclusion Criteria:

  • Type 2 diabetes mellitus
  • Hemoglobin A1C of ≥7.5% and ≤10.5%
  • Currently taking a stable dose of metformin (at least 1500 mg/day) and either glimepiride (at least 2 mg/day) or gliclazide (at least 50% of maximum registered dose) for at least 10 weeks prior to study start
  • Male, or a female who is highly unlikely to conceive

Exclusion Criteria:

  • Type 1 diabetes mellitus or ketoacidosis
  • Taking a dipeptidyl peptidase-4 (DPP-4) inhibitor (such as sitagliptin) or a glucagon-like peptide-1 (GLP-1) mimetic (such as exenatide or liraglutide) or required insulin therapy within 12 weeks prior to study start
  • On a weight loss program not in the maintenance phase or on a weight loss medication
  • History of liver disease, heart failure, heart disease, stroke, high blood pressure, blood disorders, or cancer
  • HIV positive
  • Pregnant
  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: NCT01076075

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

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01076075     History of Changes
Other Study ID Numbers: 0431-229, 2010_513, MK-0431-229
Study First Received: February 24, 2010
Results First Received: June 28, 2012
Last Updated: August 27, 2013
Health Authority: Malaysia: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
India: Ministry of Health

Keywords provided by Merck Sharp & Dohme Corp.:
Type 2 Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Pioglitazone
Sitagliptin
Gliclazide
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014