Primary Investigator: Arun Kumar, MD
Study Coordinator: Alisa Lau-Sieckman, RN
Status: Active - open to enrollment
Study Title: A randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate cardiovascular outcomes during treatment with lixisenatide in type 2 diabetic patients after an acute coronary syndrome (ACS)
Purpose: The primary objective of this study is to evaluate cardiovascular outcomes with lixisenatide compared to placebo (composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina) in type 2 diabetic patients who experienced an ACS event, at least five days and no more than 12 weeks prior to the screening visit.
1. Men and women who experienced an ACS event (i.e., ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarction [NSTEMI] or unstable angina [UA]) at least five days and no more than 12 weeks prior to the screening visit, and providing that they are discharged from the acute care facility (i.e., emergency room, intensive care unit, etc.).
2. Patients with a history of type 2 diabetes (for patients newly diagnosed, diagnosis will be based on the WHO criteria: i.e., fasting venous plasma glucose concentration ≥ 7.0 mmol/L [126 mg/dL] or two-hour post glucose load venous plasma glucose ≥ 11.1 mmol/L [200 mg/dL], confirmed on two occasions) prior to the screening visit.
Criteria for the entry into the run-in period
1. HbA1c < 6.0% or > 10.0% on last value obtained prior to the screening visit.
2. Fasting plasma glucose >13.9 mmol/L (>250 mg/dL) on last value obtained prior to the screening visit.
3. At the time of screening, age < 30 years.
4. Women of childbearing potential with no effective contraceptive method.
5. Type 1 diabetes mellitus.
6. Use of GPL-1 receptor agonists or DPP-IV inhibitors within three months prior to the screening visit.
7. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (e.g. multiple endocrine neoplasia syndromes).
8. History of metabolic acidosis, including diabetic ketoacidosis within six months prior to screening.
9. Known history of drug or alcohol abuse within 6 months prior to the time of screening.
10. Patients who have undergone a coronary artery bypass graft surgery (CABG) prior to screening, or a percutaneous coronary intervention (PCI) within 30 days prior to screening or a catheterization within 7 days prior to screening.
11. Patients with planned revascularization procedure (PCI or CABG) at the time of screening visit.
12. Conditions/situations such as:
•- Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases.
•- Patients considered by the Investigator or any sub-Investigator as inappropriate for this study for any reason, e.g.:
Those deemed unable to meet specific protocol requirements, such as scheduled visits or being able to do self-injections;
Those with likelihood of requiring treatment during the screening phase and treatment phase with drugs not permitted by the clinical study protocol; and/or
Investigator or any sub-Investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol, etc).
13. Patients who have previously participated in any clinical trial with lixisenatide.
14. Patients who have taken other investigational drugs within one month or five half-lives, whichever is longer.
Criteria related to the current knowledge of lixisenatide
1. Pregnancy or lactation.
2. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, and unstable (i.e., worsening) and not controlled (i.e., prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within six months prior to the screening visit.
3. Allergic reaction to any GLP-1 receptor agonist or to metacresol in the past.
4. Severe chronic renal insufficiency defined by a serum creatinine clearance of < 30 mL/min (calculated by the Cockroft and Gault formula).
1. Determine if patient fits major study criteria.
2. Determine if patient is interested in joining a clinical trial.
3. Call Alisa Lau-Sieckman (beeper 573-443-9259) and/or on-call research nurse (on-call beeper 573-499-8084) or Dr. Kumar to complete screening of patient.