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)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo
* Drug: Gliclazide
* Drug: Glimepiride
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin<br>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<br>* Sitagliptin 100 mg oral tablet once daily for 24 weeks<br>* Other names: MK-0431;Drug: Gliclazide<br>* Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study.<br>Drug: Glimepiride<br>* Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study.<br>Drug: Metformin<br>* Participants will continue ongoing open-label therapy with metformin (at least 1500 mg daily) throughout the study.<br>|
| Placebo Comparator: Placebo<br>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<br>* Matching placebo to sitagliptin oral tablet once daily for 24 weeks<br>Drug: Gliclazide<br>* Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study.<br>Drug: Glimepiride<br>* Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study.<br>Drug: Metformin<br>* Participants will continue ongoing open-label therapy with metformin (at least 1500 mg daily) throughout the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin | A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0. | Baseline and Week 24 | 
| Number of Participants Who Experienced an Adverse Event | 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. | Up to 26 weeks | 
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 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. | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin | This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0. | Baseline and Week 24 | 
| Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin | This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. | Baseline and Week 24 | 
| Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin | A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0. | Baseline and Week 24 | 
| Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone | A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0. | Baseline and Week 24 | 
| Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and a Sulfonylurea in Combination With Metformin | This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0. | Baseline and Week 24 | 
| Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone | This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0. | Baseline and Week 24 | 
| Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin | This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. | Baseline and Week 24 | 
| Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone | This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. | Baseline and Week 24 |