A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Sulfonylurea With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-253)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01590771
First received: May 1, 2012
Last updated: April 16, 2015
Last verified: April 2015
  Purpose

A study to compare safety and efficacy of sitagliptin and placebo therapy when added to stable sulfonylurea alone or in combination with metformin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis of this study is that after 24 weeks, the addition of sitagliptin compared with placebo provides greater reduction in hemoglobin A1C (HbA1C) in T2DM participants on sulfonylurea alone or in combination with metformin.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin
Drug: Placebo
Drug: Gliclazide
Drug: Glimepiride
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial in China to Study the Safety and Efficacy of the Addition of Sitagliptin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sulfonylurea Therapy, Alone or 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 A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

  • Number of Participants Who Experienced an Adverse Event [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: Yes ]
    An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.

  • Number of Participants Who Discontinued Study Drug Due to an Adverse Event [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]
    An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.


Secondary Outcome Measures:
  • Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.

  • Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

  • Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

  • Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.

  • Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and a Sulfonylurea in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.

  • Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.

  • Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

  • Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.


Enrollment: 498
Study Start Date: July 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Sitagliptin 100 mg once daily for 24 weeks. Participants will continue pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during run-in period.
Drug: Sitagliptin
Sitagliptin 100 mg oral tablet once daily for 24 weeks
Other Names:
  • Januvia®
  • MK-0431
Drug: Gliclazide
Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study.
Drug: Glimepiride
Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study.
Drug: Metformin
Participants will continue ongoing open-label therapy with metformin (at least 1500 mg daily) throughout the study.
Placebo Comparator: Placebo
Matching placebo once daily for 24 weeks. Participants will continue pre-study gliclazide or glimepiride with or without metformin for ≥10 weeks before and throughout the study.
Drug: Placebo
Matching placebo to sitagliptin oral tablet once daily for 24 weeks
Drug: Gliclazide
Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study.
Drug: Glimepiride
Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study.
Drug: Metformin
Participants will continue ongoing open-label therapy with metformin (at least 1500 mg daily) throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • has T2DM
  • is currently on a stable regimen of gliclazide or glimepiride, either alone or in combination with metformin for ≥ 10 weeks
  • has a Visit 1/Screening HbA1C between 7.5% and 11.0%
  • is a male, or a female who is highly unlikely to conceive during the study and for 14 days after the last dose of study medication

Exclusion Criteria:

  • has a history of type 1 diabetes mellitus or a history of ketoacidosis
  • has been treated with any antihyperglycemic therapies other than a sulfonylurea (alone or with metformin) within the prior 12 weeks or has ever

been treated with a dipeptidyl peptidase-4 inhibitor or a glucagon-like peptide-1 mimetic or analogue

  • has a history of intolerance or hypersensitivity, or has any contraindication to sitagliptin, gliclazide/glimepiride, or metformin
  • is on a weight loss program and not in the maintenance phase, or has started a weight loss medication or has undergone bariatric surgery within 12 months
  • has undergone a surgical procedure within 4 weeks or has planned major surgery during the study
  • has a medical history of active liver disease
  • has had new or worsening signs or symptoms of coronary heart disease within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder
  • has a diagnosis of congestive heart failure with New York Heart Association Class III - IV cardiac status
  • has a systolic blood pressure ≥ 160 mmHg or a diastolic blood pressure ≥ 90 mmHg
  • has human immunodeficiency virus (HIV)
  • has severe peripheral vascular disease
  • is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
  • has a history of malignancy ≤ 5 years before the study, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
  • has a clinically important hematological disorder (such as aplastic anemia,

myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

  • is pregnant or breast feeding, or is expecting to conceive or donate eggs during the study, including 14 days after the last dose of study medication
  • is a user of recreational or illicit drugs or has had a recent history of drug abuse
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01590771     History of Changes
Other Study ID Numbers: 0431-253
Study First Received: May 1, 2012
Results First Received: April 16, 2015
Last Updated: April 16, 2015
Health Authority: China: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 25, 2015