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)

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01590771
• Other study ID #: 0431-253
• Status: Completed
• Phase: Phase 3
• Start date: July 9, 2012
• Est. completion date: June 24, 2014

Study information

• Verified date: July 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 498
• Est. completion date: June 24, 2014
• Est. primary completion date: June 10, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sitagliptin
Sitagliptin 100 mg oral tablet once daily for 24 weeks
• Placebo
Matching placebo to sitagliptin oral tablet once daily for 24 weeks
• Gliclazide
Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study.
• Glimepiride
Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study.
• Metformin
Participants will continue ongoing open-label therapy with metformin (at least 1500 mg daily) throughout the study.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 wi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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