STUDY TO ASSESS CARDIOVASCULAR OUTCOMES FOLLOWING TREATMENT WITH ERTUGLIFLOZIN IN SUBJECTS WITH TYPE 2 DIABETES MELLITUS AND ESTABLISHED VASCULAR DISEASE
- Conditions
- Type 2 Diabetes MellitusMedDRA version: 20.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2013-002518-11-BG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 8000
1. Subjects = 40 years of age at the time of the initial Screening visit (V1) with a diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines.13
2. HbA1c at the Screening visit (V1) of 7.0 10.5% (53 91 mmol/mol) on stable allowable AHA(s) or on no background AHA for at least 8 weeks prior to the Screening visit (V1).
3. Body Mass Index (BMI) =18.0 kg/m2.
4. Subjects must have evidence or a history of atherosclerosis involving the coronary, cerebral or peripheral vascular systems as follows (must have at least one of the following a-d):
a. Coronary artery disease as indicated by a history of presumed spontaneous myocardial infarction (hospitalized with final diagnosis of myocardial infarction, excluding peri-procedural or definite secondary myocardial infarction [eg, due to profound anemia or hypertensive emergency, troponin increase in sepsis] in which the most recent event occurred at least 3 months (90 days) prior to the Screening visit (V1); OR
b. Coronary artery disease as indicated by a history of coronary revascularization through either a Percutaneous Coronary Intervention (PCI) at least 3 months (90 days) prior to the Screening visit (V1) or Coronary Artery Bypass Graft (CABG) at least 3 months (90 days) prior to the Screening visit (V1); OR
c. Ischemic (presumed thrombotic) cerebrovascular disease as indicated by a history of ischemic stroke (hospitalized with a final diagnosis of non hemorrhagic stroke [includes completion of a standard evaluation for stroke in an acute care facility or stroke clinic without hospital admission] with the most recent event occurring at least 3 months (90 days) prior to the Screening visit (V1) or a history of carotid revascularization at least 3 months (90 days) prior to the Screening visit (V1); OR
d. Peripheral arterial disease as indicated by:
1. Angiographically documented peripheral vascular disease; or
2. Resting ankle/brachial index (ABI) of <0.85 (measured by a certified vascular laboratory) plus symptoms of claudication; or
3. Amputation, peripheral bypass, or peripheral angioplasty of the extremities secondary to ischemia occurring at least 3 months (90 days) prior to the Screening visit (V1).
5. There is adequate documentation of the objective evidence that the subject has established vascular disease such as investigational site's medical records, copies of such records from other institutions, or a letter from a referring physician that specifically states the diagnosis and date of the most recent occurrence of the qualifying event(s) or procedure(s).
6. Subject meets one of the following criteria (a, b or c):
a. Is a male;
b. Is a female not of reproductive potential defined as one who (See Section 4.4.4.1 and Section 4.4.4.2 for reference on childbearing potential):
1. Is postmenopausal: defined as at least 12 months with no menses in women =45 years of age. or
2. Has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to the Screening visit (V1).
c. Is a female of reproductive potential and:
1. Agrees to remain abstinent from heterosexual activity (if this form of birth control is accepted by local regulatory agencies and ethics review committees as the sole method of birth control); or
2. Agrees to use (or have their partner use) acceptable contraception to prevent pregnancy while the subject is receiving investigational product and for 14 days after the last dose of investigational pr
1.Subjects who had been previously randomized into this trial.
2.Subjects experiencing a cardiovascular event(eg,myocardial infarction or stroke)or undergoing coronary angioplasty or peripheral intervention procedure between the Screening visit(V1) and randomization.
3.Subjects undergoing any cardiovascular surgery(eg,valvular surgery)within 3 months(90 days)of the Screening visit(V1).
4.Subjects with any planned coronary revascularization or peripheral intervention procedure or other cardiovascular surgery.
5.Subjects with New York Heart Association(NYHA) Class IV heart failure at the Screening visit(V1).
6.Mean value for triplicate screening sitting systolic blood pressure>160mm Hg and/or diastolic blood pressure>90mm Hg after at least a 5 minute seated rest at the Screening visit(V1), confirmed via 1 repeat triplicate set at the Screening visit(V1) if deemed necessary. For subjects with a mean triplicate value of sitting systolic blood pressure >160mm Hg and/or diastolic blood pressure>90mm Hg after at least a 5 minute seated rest at the Screening visit(V1) the investigator or the treating physician is allowed to adjust background blood pressure medication(s) to lower blood pressure values in order for the subject to be re-assessed for enrollment eligibility.
7.Subject has a clinically significant ECG abnormality at Screening visit(V1) that requires further diagnostic evaluation or intervention(eg,new,clinically significant arrhythmia or a conduction disturbance).
8.History of type 1 diabetes mellitus or a history of ketoacidosis.
9.History of other specific types of diabetes (eg, genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical induced, and post organ transplant).
10.Subject has active, obstructive uropathy or indwelling urinary catheter.
11.Subject has a history of malignancy =5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
Note(1) A subject with a history of malignancy>5 years prior to signing informed consent should have no evidence of residual or recurrent disease.
Note(2) A subject with any history of melanoma, leukemia, lymphoma, or renal cell carcinoma is excluded.
12.Subject routinely consumes>2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking.
Note(1): One alcoholic drink is defined as 5 oz (150 mL) of wine, or 12 oz(350 mL) of beer,or 1.5 oz (50 mL)of 80 proof liquor.
Note(2): Binge drinking is defined as a pattern of 5 or more alcoholic drinks (male), or 4 or more alcoholic drinks (female) in about 2 hours.
13.Any clinically significant malabsorption condition.
14.Subjects with a known hypersensitivity or intolerance to any SGLT2 inhibitor.
15.Screening fasting plasma or finger stick glucose >270 mg/dL(15 mmol/L), confirmed by a single repeat following counseling on exercise and diet.
16.History of one or more severe hypoglycemic episodes within 6 months of Screening(V1) or a severe hypoglycemic episode occurring during the interval between the Screening visit(V1) and randomization.
17.Fasting triglycerides >600 mg/dL(6.78 mmol/L) at Screening(V1), confirmed by a single repeat if deemed necessary. For subjects with fasting triglycerides >600mg/dL the investigator or treating physician is allowed to adjust background lipid altering medication(s) to lower fasting triglycerides in order for the subject to be re-assessed for enr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method