Cardiovascular events in patients with Type 2 diabetes MedDRA version: 19.1 Level: HLT Classification code 10012654 Term: Diabetic complications cardiovascular System Organ Class: 100000004860
Conditions
Interventions
Trade Name: Trulicity
Product Name: Dulaglutide
Product Code: LY2189265
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: [1] Men or women with type 2 diabetes based on: a) a previous diagnosis of type 2 diabetes; or b) newly detected type 2 diabetes based on the American Diabetes Association criteria (ADA 2011) as either two of the following criteria or one of the following criteria that is confirmed on a second day: - fasting plasma glucose =7.0 mmol/L (126 mg/dL), or - 2-hour plasma glucose =11.1 mmol/L (200 mg/dL) following a 75-gram oral glucose load, as described by the World Health Organization (WHO 2006), or - HbA1c =6.5% (=48 mmol/mol) [2] HbA1c value of =9.5% (=81 mmol/mol) at screening [3] Are taking: a) no glucose-lowering drugs; OR b) 1 or 2 classes of oral glucose-lowering drugs; with or without basal insulin daily [as defined below in (d)]; if one of the oral glucose-lowering drugs is a DPP-IV inhibitor, the patient must be willing to stop the DPP-IV inhibitor after eligibility is confirmed; OR c) 1 or 2 classes of oral glucose-lowering drugs with a GLP-1 analog; with or without basal insulin daily [as defined below in (d)]; the patient must be willing to stop the GLP-1 analog after eligibility is confirmed; OR d) basal insulin daily defined as 1 to 2 injections per day of either glargine, determir, neutral protamine Hagedorn (NPH), or another approved basal insulin. [4] No change in the number or class of glucose-lowering drugs, no change in excess of doubling or halving the dose of these drugs, and if on insulin, no change in the dose of insulin in excess of 20% of the average daily dose, for at least 3 months before screening [5] If age =50 years and established clinical vascular disease defined as 1 or more of the following: - a history of MI - a history of ischemic stroke - a history of coronary, carotid, or peripheral artery revascularization. If prior coronary artery bypass grafting (CABG), the CABG should have been performed >2 years prior to randomization. If prior carotid or peripheral artery revascularization, the revascularization should have been performed >2 years prior to randomization. - hospitalization for unstable angina with ECG changes (new or worsening ST or T wave changes), or myocardial ischemia on imaging, or need for percutaneous coronary intervention (PCI); OR - If age =55 years and subclinical vascular disease defined as 1 or more of the following: - a history of myocardial ischemia by a stress test or with cardiac imaging, with or without history of exertional angina - >50% vascular stenosis with imaging of the coronary, carotid, or lower extremity arteries, with or without claudication history - ankle-brachial index <0.9 - 2 consecutive values or a documented history of persistent eGFR<60 mL/minute/1.73m2 - a history of hypertension with documented LV hypertrophy on an ECG or echocardiogram - documented history of persistent microalbuminuria or macroalbuminuria; or 2 consecutive urine samples demonstrating micro- or macroalbuminuria OR - If age
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria: [1] Uncontrolled diabetes requiring immediate therapy (such as diabetic ketoacidosis) at screening or randomization, in the judgment of the physician. [2] Have experienced a severe hypoglycemic episode within 1 year prior to randomization. [3] Have experienced an acute coronary or cerebrovascular event within 2 months prior to randomization. [4] Are currently planning a coronary, carotid, or peripheral artery revascularization. [5] Have known chronic renal failure (defined as a known eGFR <15 mL/minute/1.73m2) or are on chronic dialysis at screening. [6] Have a known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction) or have undergone gastric bypass (such as bariatric) surgery. [7] Have a past history of chronic, acute, or idiopathic pancreatitis or signs/symptoms of pancreatitis. [8] Have severe hepatic dysfunction such as portal hypertension or cirrhosis, acute or chronic hepatitis, signs or symptoms of any other liver disease, or an alanine transaminase (ALT) level =3.0 times the upper limit of normal (ULN) for the reference range at screening. [9] Have a) any self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial or part of multiple endocrine neoplasia MEN 2A or 2B syndrome), or b) any known self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia. This includes patients with a family history of MEN 2A or 2B whose family history for the syndrome is RET negative. The only exception for this exclusion will be patients whose family members with MEN 2A or 2B have a known RET mutation and the potential patient for the study is negative for that RET mutation. [10] Have a calcitonin value =20 pg/mL according to the central laboratory measurement at screening. [11] Are previous organ transplant recipients or are awaiting an organ transplant (corneal transplants [keratoplasty] are allowed). [12] Are taking a weight loss drug (over-the-counter or prescription) and are unwilling or unable to discontinue the drug at the time of screening or are taking pramlintide at the time of screening. [13] History of, an active, or untreated malignancy, in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years prior to, or are receiving or planning to receive therapy for cancer, at screening. [14] Females who are pregnant or have a positive pregnancy test at screening, or who have given birth within the past 90 days, or who are breastfeeding. [15] Females of childbearing potential (that is, females who are between menarche and less than 1-year past the last menses with an intact uterus) who do not agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. Menopause is the absence of menses for =1 year and/or surgically or chemically induced. [16] Are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to test the hypothesis that once-weekly injection of 1.5-mg Dulaglutide reduces the occurrence of the composite primary endpoint of death from CV causes, nonfatal myocardial infarction (MI), or nonfatal stroke when added to the glucose-lowering regimen of patients with type 2 diabetes, compared to the addition of a once-weekly placebo injection. ; Secondary Objective: The secondary efficacy objectives are to assess the effects of add-on therapy with 1.5-mg Dulaglutide compared to placebo on the occurence of: - the composite microvascular endpoint of diabetic retinopathy requiring laser therapy, vitrectomy, or anti-VEGF therapy, development of clinical proteinuria, a 30% decline in estimated glomerular filtration rate (eGFR), or need for chronic renal replacement therapy - hospitalization for unstable angina - each component of the composite primary endpoint - all cause mortality - heart failure (HF) requiring hospitalization or an urgent HF visit The prespecified safety objectives are to assess the effects of add-on therapy with 1.5-mg Dulaglutide compared to placebo on the incidence of: - acute pancreatitis - any cancer (excluding basal and squamous cell skin cancer) - medullary thyroid carcinoma (MTC) - C-cell hyperplasia - discontinuation of study drug for any reason - severe hypoglycemia - allergic/hypersensitivity reactions ;Primary end point(s): The primary efficacy measure is the time to first occurrence (after randomization) of the composite of death from CV causes, nonfatal MI, or nonfatal stroke.;Timepoint(s) of evaluation of this end point: Throughout the duration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy measures include time (after randomization) to: - first occurrence of the composite microvascular endpoint of diabetic retinopathy requiring laser therapy, vitrectomy or anti-VEGF therapy, development of clinical proteinuria, a 30% decline in estimated glomerular filtration rate (eGFR), or need for chronic renal replacement therapy - first hospitalization for unstable angina - first occurrence of each component of the composite primary endpoint - death -first occurrence of heart failure (HF) requiring hospitalization or an urgent HF visit ;Timepoint(s) of evaluation of this end point: Throughout the duration of the study | — |
Countries
Argentina, Australia, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Germany, Hungary, India, Korea, Democratic People's Republic of, Latvia, Lithuania, Mexico, New Zealand, Peru, Poland, Romania, Russian Federation, South Africa, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly and Company
Outcome results
None listed