Clinical trial NCT02532855: A Study to Assess the Addition of Sitagliptin to Metformin Compared With the Addition of Dapagliflozin to Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) and Mild Renal Impairment Who Have Inadequate Glycemic Control on Metformin With or Without a Sulfonylurea (MK-0431-838)
Official title: A Phase III, Multicenter, Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety and Efficacy of the Addition of Sitagliptin Compared With the Addition of Dapagliflozin in Subjects With Type 2 Diabetes Mellitus and Mild Renal Impairment Who Have Inadequate Glycemic Control on Metformin With or Without a Sulfonylurea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-08-26
Enrollment: 614
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the effect of the addition of sitagliptin to metformin with or without a sulfonylurea compared with the addition of dapagliflozin to metformin with or without a sulfonylurea on hemoglobin A1c (A1C) over 24 weeks of treatment as well as the overall safety and tolerability of sitagliptin in comparison to that of dapagliflozin after 24 weeks of treatment. The primary hypothesis is that the change from baseline in A1C in participants treated with the addition of sitagliptin is non-inferior compared to that in participants treated with the addition of dapagliflozin after 24 weeks of treatment.


Eligibility criteria: Inclusion Criteria

* Have T2DM at Screening visit
* Be on metformin monotherapy ≥1500 mg/day alone or in combination with an sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) for ≥8 weeks
* Is a male or a female not of reproductive potential (defined as one who is postmenopausal or has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to Screening visit). If participant is a female of reproductive potential, must agree to remain abstinent from heterosexual activity or agrees to use (or have her partner use) acceptable contraception to prevent pregnancy while receiving blinded study drug and for 14 days after the last dose of blinded study drug

Exclusion Criteria:

* Has a history of type 1 diabetes mellitus or a history of ketoacidosis
* Has a history of secondary causes of diabetes
* Has a known hypersensitivity or intolerance to any dipeptidyl peptidase IV (DPP-4) inhibitor or sodium-glucose cotransporter 2 (SGLT2) inhibitor
* Has been treated with any anti-hyperglycemic agents (AHA) other than metformin and for participants on dual combination therapy, a sulfonylurea within 12 weeks of screening
* Intends to initiate weight loss medication during the study period
* Has undergone bariatric surgery within 12 months of Screening visit
* Has started a weight loss medication or a medication associated with weight changes within the prior 12 weeks.
* Has a history of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, heart failure within 3 months of Screening visit
* Has a history of malignancy ≤5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
* Has human immunodeficiency virus (HIV)
* Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells, or clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
* Has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
* Is currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks prior to Screening visit
* Is on or likely to require treatment for ≥14 consecutive days or repeated courses of corticosteroids
* Is on or likely to require treatment for ≥7 consecutive days with non-steroidal anti-inflammatory drugs
* Is pregnant or breast-feeding, or is planning to conceive during the study, including 14 days following the last dose of blinded study drug
* Is planning to undergo hormonal therapy in preparation to donate eggs during the study, including 14 days following the last dose of blinded study drug
* Routinely consumes \>2 alcoholic drinks per day or \>14 alcoholic drinks per week or engages in binge drinking
* Has donated blood or blood products within 6 weeks of Screening visit or who plans to donate blood or blood products at any time during the study

Primary outcomes:
measure: Change From Baseline in A1C at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Who Experienced One or More Adverse Events
timeFrame: Up to 26 weeks
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Change From Baseline in Incremental 2-hour (2-hr) Postprandial Glucose Excursion (PPGE) at Week 24
timeFrame: Immediately before and 120 minutes after the standard meal at Baseline and Week 24
measure: Change From Baseline in 2-hr Postprandial Glucose (PPG) at Week 24
timeFrame: Immediately before and 120 minutes after the standard meal at Baseline and Week 24
measure: Change From Baseline in Glucagon Area Under the Curve (AUC0-120 Minutes) at Week 24
timeFrame: Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24
measure: Change From Baseline in Insulin AUC0-120 Minutes at Week 24
timeFrame: Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24
measure: Change From Baseline in Postprandial Insulin AUC0-120 Minutes to Glucagon AUC0-120 Minutes Ratio at Week 24
timeFrame: Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24
measure: Percentage of Participants With A1C <7% (53 mmol/Mol) at Week 24
timeFrame: Week 24
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Scott R, Morgan J, Zimmer Z, Lam RLH, O'Neill EA, Kaufman KD, Engel SS, Raji A. A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT-R study. Diabetes Obes Metab. 2018 Dec;20(12):2876-2884. doi: 10.1111/dom.13473. Epub 2018 Aug 16.