A Study in China Evaluating the Safety and Efficacy of Adding Sitagliptin to Stable Therapy With Insulin With or Without Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-254)

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 Insulin Therapy, Alone or in Combination With Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01590797
• Other study ID #: 0431-254
• Status: Completed
• Phase: Phase 3
• Start date: July 10, 2012
• Est. completion date: June 25, 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 insulin 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 insulin alone or in combination with metformin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 467
• Est. completion date: June 25, 2014
• Est. primary completion date: June 11, 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 pre-mixed, intermediate-acting, or long-acting insulin at a dose of at least 12 U/day, either alone or in combination with metformin >=1500 mg/day 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 been treated with any antihyperglycemic therapies other than a protocol-required insulin (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

• is currently on treatment with daily use (one or more injections per day) of

pre-prandial short-acting or rapid-acting insulin

• has a history of 2 or more episodes of hypoglycemia resulting in seizure,

coma, or loss of consciousness, or has had recurrent episodes of hypoglycemia over the past 8 weeks

• has a history of intolerance or hypersensitivity, or has any contraindication to sitagliptin, insulin, 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 once daily for 24 weeks
• Placebo
Matching placebo once daily for 24 weeks

Biological:
• Insulin
Participants can be on on pre-mixed (mixture of rapid- and long-acting insulin) or intermediate- or long-acting insulin at a dose of at least 12 U/day.

Drug:
• Metformin
At randomization, participants will be stratified according to their use of metformin (on or not on). All participants receiving metformin will be required to be on a daily dose of metformin at least 1500 mg per day.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

Shankar RR, Bao Y, Han P, Hu J, Ma J, Peng Y, Wu F, Xu L, Engel SS, Jia W. Sitagliptin added to stable insulin therapy with or without metformin in Chinese patients with type 2 diabetes. J Diabetes Investig. 2017 May;8(3):321-329. doi: 10.1111/jdi.12585. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin		Baseline and Week 24
Primary	Number of Participants With One or More Adverse Events	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to Week 26
Primary	Number of Participants Discontinuing Study Medication Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to Week 24
Secondary	Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin		Baseline and Week 24
Secondary	Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin		Baseline and Week 24