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)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sitagliptin
Placebo
Gliclazide
Glimepiride
Metformin
Sponsored by

About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sitagliptin
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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
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
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
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
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
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
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
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
This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01590771
Brief Title
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)
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 9, 2012 (Actual)
Primary Completion Date
June 10, 2014 (Actual)
Study Completion Date
June 24, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
498 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitagliptin
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
Januvia®, MK-0431
Intervention Description
Sitagliptin 100 mg oral tablet once daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to sitagliptin oral tablet once daily for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Gliclazide
Intervention Description
Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study.
Intervention Type
Drug
Intervention Name(s)
Glimepiride
Intervention Description
Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Participants will continue ongoing open-label therapy with metformin (at least 1500 mg daily) throughout the study.
Primary Outcome Measure Information:
Title
Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin
Description
A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.
Time Frame
Baseline and Week 24
Title
Number of Participants Who Experienced an Adverse Event
Description
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.
Time Frame
Up to 26 weeks
Title
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Description
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.
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin
Description
This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin
Description
This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin
Description
A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone
Description
A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and a Sulfonylurea in Combination With Metformin
Description
This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone
Description
This change from baseline reflects the 2-hr PMG level at Week 24 minus the 2-hr PMG level at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin
Description
This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.
Time Frame
Baseline and Week 24
Title
Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone
Description
This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.
Time Frame
Baseline and Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility 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
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
27502307
Citation
Ba J, Han P, Yuan G, Mo Z, Pan C, Wu F, Xu L, Hanson ME, Engel SS, Shankar RR. Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined with metformin. J Diabetes. 2017 Jul;9(7):667-676. doi: 10.1111/1753-0407.12456. Epub 2016 Sep 13.
Results Reference
result
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0431-253&kw=0431-253&tab=access
Learn more about this trial
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)
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