A randomized double blind, placebo-controlled clinical trial to assess the effects of taspoglutide (RO5073031) on cardiovascular outcomes in subjects with inadequately controlled type 2 diabetes and established cardiovascular disease - T-EMERGE 8

INTERVENTION: Product Name: Taspoglutide Product Code: RO5073031/F04‐04 Pharmaceutical Form: Solution for injection INN or Proposed INN: Taspoglutide CAS Number: 275371‐94‐3 Current Sponsor code: RO5073031/F04‐04 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: Taspoglutide Product Code: RO5073031/F04‐01 Pharmaceutical Form: Solution for injection INN or Proposed INN: Taspoglutide CAS Number: 275371‐94‐3 Current Sponsor code: RO5073031/F04‐01 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: Patients with Type 2 diabetes ; MedDRA version: 12.0 Level: LLT Classification code 10067585 Term: Type 2 diabetes mellitus PRIMARY OUTCOME: Main Objective: The primary objective is to determine the effect of taspoglutide in addition to standard of care on cardiovascular outcomes in type 2 diabetic subjects with established cardiovascular disease in order to rule out an unacceptable (80%) increase in cardiovascular events.; Primary end point(s): The primary endpoint of the study is the time to first occurrence of any component of a cardiovascular composite endpoint (CV death, MI, stroke, resuscitated cardiac arrest, hospitalization for unstable angina or hospitalization for heart failure) adjudicated by an independent cardiovascular event adjudication committee; (CV‐EAC). For this primary cardiovascular endpoint a noninferiority test will be applied to the data from the intent‐to‐treat (ITT) population to confirm the hypothesis that the hazard ratio comparing the taspoglutide and placebo groups falls below and excludes a 1.80 upper bound of the 95% confidence interval.; Therefore, if the upper limit of the 95% CI of the HR is less than 1.80, non‐inferiority will be concluded. If this initial objective is met the trial may be adapted, using existing statistical methods, with increases in the sample size and study duration in order to exclude, in sequence, a 30% increase in cardiovascular events (i.e. the upper 95% CI being less than a HR = 1.3) followed by (if met) an assessment of superiority. Secondary Objective: To assess the effects of taspoglutide in addition to standard of care on:; • A secondary CV composite endpoint: the individual components of the composite primary endpoint plus any revascularization procedure and hospitalization for other CV events; • Each of individual components of the composite CV primary endpoint; • Total mortality; • Metabolic and renal function parameters INCLUSION CRITERIA: 1. Men and women > 18 years old at screening. Women of childbearing potential will be required to use two approved birth control methods during the entire course of the study. 2. Known type 2 diabetes (T2D) or newly diagnosed T2D according to the 1997 American Diabetes Association diagnostic criteria* *Fasting plasma glucose (FPG) values =126 mg/dl, or symptomatic hyperglycemia and a casual glucose =200 mg/dl OR 2‐h plasma glucose =200 mg/dl after a 75 g oral glucose load Diabetes may be managed with diet alone, or with any approved glucose‐lowering therapies except for those listed in exclusion criteria 11 and 12. The diabetes reatment will follow the local usual standard of care 3. HbA1C =6.5% and =10% at screening 4. Body mass index (BMI) = 23 kg/m2 at screening 5. Subjects with established cardiovascular (CV) disease with onset =1 month prior to screening and who are stable in the Investigator’s judgment, based on the presence of at least o