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)

NCT ID: NCT01590797

Last Updated: 2018-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 467 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-10
• Study Completion Date: 2014-06-25

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Sitagliptin

Participants treated with sitagliptin 100 mg, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Sitagliptin 100 mg once daily for 24 weeks

Insulin

Intervention Type: BIOLOGICAL

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.

Metformin

Intervention Type: DRUG

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.

Placebo

Participants treated with placebo matching sitagliptin, once daily, for 24 weeks. All participants will be under treatment with a stable dose of insulin with or without metformin for ≥10 weeks before and throughout the study. All participants will receive placebo during the Placebo Run-in period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo once daily for 24 weeks

Insulin

Intervention Type: BIOLOGICAL

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.

Metformin

Intervention Type: DRUG

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.

Interventions

Sitagliptin

Sitagliptin 100 mg once daily for 24 weeks

Intervention Type: DRUG

Placebo

Matching placebo once daily for 24 weeks

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Other Intervention Names

Januvia®; MK-0431

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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. Epub 2016 Dec 9.

Reference Type: RESULT

PMID: 27740719 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

0431-254

Identifier Type: -

Identifier Source: org_study_id