Type 2 diabetes mellitus MedDRA version: 21.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Men or women at least 40 years old with a diagnosis of T2DM (WHO 2019). [2] Established CVD, including at least 1 of the following (a-c): a. Coronary artery disease (CAD) with ANY of the following: - Documented history of spontaneous MI - =50% stenosis in 1 or more major coronary arteries, determined by invasive angiography - =50% stenosis in 2 or more major coronary arteries, determined by computed tomography coronary angiography (CTCA), or - History of surgical or percutaneous coronary revascularization procedure; b. Cerebrovascular disease – ANY of the following: - Documented history of ischemic stroke - Carotid arterial disease with =50% stenosis, documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography - Carotid stenting or surgical revascularization; c. Peripheral arterial disease with EITHER of the following: - Intermittent claudication and ankle-brachial index =65 years) yes F.1.3.1 Number of subjects for this age range 6250
Exclusion criteria
Exclusion criteria: [8] Have type 1 diabetes mellitus. [9] Have uncontrolled diabetes requiring immediate therapy (such as diabetic ketoacidosis) at screening or randomization, in the judgment of the physician. [10] Have had 1 or more events of severe hypoglycemia and/or 1 or more events of hypoglycemia unawareness within 6 months prior to screening. [11] Are currently planning treatment for diabetic retinopathy and/or macular edema. [12] Have been hospitalized for CHF within 2 months prior to screening. [13] Have chronic New York Heart Association Functional Classification IV CHF. [14] Are currently planning a coronary, carotid, or peripheral artery revascularization. [15] Had chronic or acute pancreatitis any time prior to screening, irrespective of etiology. [16] Have a known clinically significant gastric emptying abnormality such as severe gastroparesis or gastric outlet obstruction or have undergone or currently planning any gastric bypass (bariatric) surgery or restrictive bariatric surgery. [17] Have acute or chronic hepatitis, signs or symptoms of any other liver disease, an alanine aminotransferase (ALT) level =3X the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. [18] Have known chronic severe renal failure (defined as a known eGFR <15 mL/minute/1.73 m2) or are on chronic dialysis. [19] Have evidence of a significant, uncontrolled endocrine abnormality (eg, thyrotoxicosis or adrenal crises). [20] Have a family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (MTC) or personal history of nonfamilial MTC. [21] Have a serum calcitonin level at screening of: (based on central laboratory results) - =20 ng/L at Visit 1, if eGFR =60 mL/min/1.73 m2, or - =35 ng/L at Visit 1, if eGFR <60 mL/min/1.73 m2. [22] Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years. An exception for this criterion is basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer. [23] Have a history of any other condition (such as known drug or alcohol abuse or psychiatric disorder) that, in the opinion of the investigator, may preclude the patient from following and completing the protocol. [24] Have had a transplanted organ (corneal transplants [keratoplasty] allowed) or awaiting an organ transplant. [25] Have any other condition (eg, hypersensitivity) that is a contraindication to any incretin or GLP-1 RAs. [26] Have had an MI, percutaneous coronary revascularization procedure, ischemic stroke, carotid stenting or surgical revascularization, nontraumatic amputation or peripheral vascular procedure (eg, stenting or surgical revascularization) less than 60 days prior to screening. [27] Have had coronary artery bypass graft surgery less than 5 years prior to Screening. [37] Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hematological conditions that may interfere with HbA1c measurement. [28] Treatment with GLP-1 RA, or pramlintide in a period of 3 months prior to Visit 1. [29] Discontinuation of GLP-1 RA, or pramlintide due to intolerability any time prior to Visit 1. [30] Exclusion Criterion [30] has been deleted. [31] Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with thi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy of maximally tolerated tirzepatide dose up to 15 mg QW compared to QW dulaglutide 1.5 mg on time to first occurrence of the composite endpoint of death from CV causes, MI, or stroke (MACE-3) when both are added to standard of care in patients with T2DM and high CV risk. Primary analysis will be an assessment of NI of tirzepatide to dulaglutide for MACE-3. After establishing NI, superiority of tirzepatide compared to dulaglutide for MACE-3 will be evaluated. ;Secondary Objective: To assess the superiority of tirzepatide up to 15 mg QW compared to dulaglutide 1.5 mg QW for time to death due to any cause, time to CV death, time to first occurrence of MI and time to first occurrence of stroke. ;Primary end point(s): Time to first occurrence of a component event of a MACE-3. ;Timepoint(s) of evaluation of this end point: An independent CEC will adjudicate all primary endpoint events. The primary endpoint is the time from randomization to first occurrence of CEC-confirmed CV death, MI, or stroke. Patients will be followed until approximately 1615 patients experience at least 1 component of the primary composite endpoint of CV death, MI, or stroke. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary efficacy measures are: • Time to death due to any cause; • Time to CV death; • Time to first occurrence of MI; • Time to first occurrence of stroke. • Time to first occurrence of the expanded composite CV outcome, defined as either CV death, MI, stroke, coronary revascularization, hospitalization for unstable angina • Cumulative number of CV deaths and total (first and recurrent) HF events requiring hospitalization and/or urgent HF visits Additional secondary measures are: • Proportion of patients with more than 10% weight loss from screening after 36 months; • Change from baseline in: o weight, BMI, and waist circumference o HbA1c o urinary albumin to creatinine ratio o blood lipids: total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides; • Time to first occurrence of: o coronary, carotid, or peripheral revascularizations, individually and as composite o hospitalization due to unstable angina o composite endpoint of new or worsening nephropathy • Cumulative number of primary composite events of CV death and total (first and recurrent) MI and/or stroke; • Cumulative number of CV deaths and total (first and recurrent) HF events requiring hospitalization and/or urgent HF visits. Maximally tolerated tirzepatide dose will be measured based on: • Incidence of TEAEs and permanent discontinuation of study drug due to AEs • Incidence of: o pancreatitis o severe gastrointestinal events o any malignancy (including medullary and papillary thyroid cancers) o severe hypoglycemic events o immune-mediated reactions including serious allergic and hypersensitivity reactions o hepatobiliary events (eg, acute cholecystitis, acute cholelithiasis and drug-induced liver injury) o acute renal failure or exacerbation of chronic renal failure o diabetic retinopathy complications o supraventricular arrhythmias and cardiac conduction disorders • Mean change from baseline: o blood | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed