Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes

Treatments: Drug: Placebo matching with Sitagliptin; Drug: Placebo matching with Dapagliflozin; Drug: Placebo matching with Saxagliptin; Drug: Dapagliflozin; Drug: Sitagliptin; Drug: Saxagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02284893

CV181-363

2014-001102-17 (EudraCT Number)

Details and patient eligibility

About

Study will evaluate if a combination of saxagliptin and dapagliflozin added concurrently to metformin in combination with diet and exercise is superior to sitagliptin added to metformin in combination with diet and exercise in reducing mean HbA1c over a treatment period of 26 weeks.

Enrollment: 461 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control, defined as a central laboratory glycosylated hemoglobin (HbA1c) ≥8.0% and ≤ 10.5 % obtained at the screening visit
• Subjects should have been taking the same daily dose of metformin ≥ 1500 mg for at least 8 weeks prior to the enrollment visit and with no intake of other antihyperglycemic therapy for more than 14 days (consecutive or not) during 12 weeks prior to screening
• BMI > 20.0 kg/m2 at the enrollment visit
• Males and Females, age ≥18 years old at time of screening visit
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug
• Women must not be breastfeeding

Exclusion Criteria:

• Clinically diagnosed with Type I diabetes, known diagnosis of Maturity Onset Diabetes of Young (MODY), secondary diabetes mellitus or diabetes insipidus

• History of diabetic ketoacidosis

• Any of the following cardiovascular (CV)/Vascular Diseases within 3 months of the enrollment visit

  • Myocardial infarction
  • Cardiac surgery or revascularization (coronary artery bypass surgery Coronary Artery Bypass Graft [(CABG)]/percutaneous transluminal coronary angioplasty percutaneous transluminal coronary angioplasty [(PTCA)])
  • Unstable angina
  • Unstable congestive heart failure (CHF)
  • Transient ischemic attack (TIA) or significant cerebrovascular disease
  • Unstable or previously undiagnosed arrhythmia
  • Congestive heart failure, defined as New York Heart Association (NYHA) Class III and IV, unstable or acute congestive heart failure and/or known left ventricular ejection fraction of ≤ 40%

• Renal Disease

• Hepatic Diseases

• Hematological and Oncological Disease/Conditions

• Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women

• Abnormal Free T4

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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461 participants in 2 patient groups

A1:Saxagliptin / Placebo + Dapagliflozin / Placebo

Experimental group

Description:

Saxagliptin 5 mg and matching placebo 0 mg (once daily) plus Dapagliflozin 10 mg and matching placebo 0 mg (once daily)

Treatment:

Drug: Saxagliptin

Drug: Placebo matching with Saxagliptin

Drug: Placebo matching with Dapagliflozin

Drug: Dapagliflozin

A2: Sitagliptin / placebo

Experimental group

Description:

Sitagliptin 100 mg and matching placebo 0 mg (once daily)

Treatment:

Drug: Sitagliptin

Drug: Placebo matching with Sitagliptin