Clinical trial NCT01590797: 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)
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
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: 467
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 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.


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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1C (HbA1C) Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Number of Participants With One or More Adverse Events
timeFrame: Up to Week 26
measure: Number of Participants Discontinuing Study Medication Due to an AE
timeFrame: Up to Week 24
Secondary outcomes:
measure: Change From Baseline in HbA1C Levels at Week 24 in Participants Receiving Insulin in Combination With Metformin
timeFrame: Baseline and Week 24
measure: Change From Baseline in 2-Hour Post Meal Glucose Levels at Week 24 in Participants Receiving Insulin Alone or in Combination With Metformin
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.