Clinical trial NCT01590771: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-05-03
Enrollment: 498
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Number of Participants Who Experienced an Adverse Event
timeFrame: Up to 26 weeks
measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone or in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Change From Baseline in A1C Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone
timeFrame: Baseline and Week 24
measure: Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and a Sulfonylurea in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Change From Baseline in 2-hr PMG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone
timeFrame: Baseline and Week 24
measure: Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Change From Baseline in FPG Levels at Week 24 in Participants Receiving Sitagliptin and Sulfonylurea Alone
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
Study officials:
References:
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.