Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With AVE0010 (Lixisenatide) (ELIXA)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Acute Coronary Syndrome

Treatments: Drug: Placebo; Drug: Lixisenatide (AVE0010)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01147250

EFC11319

2009-012852-26 (EudraCT Number)

U1111-1116-5558 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

• To demonstrate that lixisenatide can reduce cardiovascular (CV) morbidity and mortality (composite endpoint of CV death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina) compared to placebo in type 2 diabetic participants who recently experienced an acute coronary syndrome (ACS) event.

Secondary Objectives:

To demonstrate that when compared to placebo, lixisenatide can reduce:

• composite endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, or hospitalization for heart failure.
• composite endpoint of CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization procedure.
• urinary albumin excretion (based on the urinary albumin/creatinine ratio).

To assess the safety and tolerability of lixisenatide.

Full description

The estimated maximum study duration for the first randomized participant was approximately 204 weeks (± 14 days), with a median follow-up over all participants of approximately 91 weeks, broken down as follows:

• placebo-run-in period: 7 days (+ 3 days)
• double-blind study treatment period: 203 weeks (± 14 days) (with about a 37 months of recruitment period)
• post-treatment follow-up period: 3 days (± 1 day)

All participants were followed from randomization until the end of study, which should occur when the last randomized participant had been followed for approximately 10 months. The actual end date of the study was "event driven" and the study end when there were approximately 844 positively-adjudicated primary cardiovascular outcome events.

Enrollment: 6,068 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men and women who experienced a spontaneous ACS event (i.e., ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation MI (NSTEMI) or unstable angina) with a documented elevation above the normal reference range of a cardiac biomarker (Troponin or Creatinine Kinase (CK)-MB) and the clinical presentation consistent with an ACS which lead to admission to an acute care facility, within 180 days following the ACS event and prior to screening.
• Participants with a history of type 2 diabetes (for participants newly diagnosed, diagnosis was based on the World Health Organization (WHO) criteria: i.e., either a fasting venous plasma glucose concentration ≥ 7.0 mmol/L [126 mg/dL] or 2-hour post glucose load venous plasma glucose ≥ 11.1 mmol/L [200 mg/dL], confirmed on 2 occasions) prior to the screening visit.

Exclusion criteria

• Type 1 diabetes mellitus or history of ketoacidosis within 6 months prior to screening.
• Glycosylated hemoglobin (HbA1c) <5.5 % or >11% measured at screening visit.
• Required to use incretin-based agents (e.g., Glucagon-like peptide -1 (GLP-1) agonists or Dipeptidyl Peptidase-4 (DPP-4) inhibitors) other than the study drug during the double-blind treatment period.
• Participants who had undergone coronary artery bypass graft (CABG) surgery following the qualifying ACS event.
• Participants who had undergone percutaneous coronary intervention (PCI) within 15 days prior to screening.
• Participants with planned revascularization procedure (PCI or CABG) or coronary angiogram within 90 days after screening visit.
• 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).
• 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.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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6,068 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo matched to lixisenatide once daily (QD) up to end of treatment.

Treatment:

Drug: Placebo

Lixisenatide

Experimental group

Description:

Lixisenatide 10 mcg QD for 2 weeks post-randomization, then at a maintenance dose of 20 mcg QD up to end of treatment.

Treatment:

Drug: Lixisenatide (AVE0010)