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

Sponsor:	Sanofi-Aventis
Information provided by (Responsible Party):	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT01147250

Purpose

Primary Objective:

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

Secondary Objectives:

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

composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, or hospitalization for heart failure
composite endpoint of cardiovascular 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.

Condition	Intervention	Phase
Acute Coronary Syndrome	Drug: lixisenatide (AVE0010) Drug: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official 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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Angina Heart Failure

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome Measures:

Time to the first occurrence of the primary cardiovascular (CV) event: CV death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, positively adjudicated by the Cardiovascular Events Adjudication Committee (CAC) [ Time Frame: week 0 to week 203 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to the first occurrence of cardiovascular (CV) death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure positively adjudicated by the CAC [ Time Frame: week 0 to week 203 ] [ Designated as safety issue: No ]
Time to the first occurrence of cardiovascular (CV) death, non-fatal MI, non-fatal stroke, hospitalization for unstable angina, hospitalization for heart failure, coronary revascularization procedure positively adjudicated by the CAC [ Time Frame: week 0 to week 203 ] [ Designated as safety issue: No ]
Percent change in the urinary albumin/creatinine ratio [ Time Frame: From baseline to 108 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	6000
Study Start Date:	June 2010
Estimated Study Completion Date:	May 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lixisenatide Titration period (week 0 to 2): 10 µg lixisenatide (0.10 mL injection) once a day in the morning within 1 hour prior to breakfast Maintenance period (week 2 to 176): 20 µg lixisenatide (0.20 mL injection) once a day in the morning within 1 hour prior to breakfast	Drug: lixisenatide (AVE0010) Pharmaceutical form:sterile aqueous solution Route of administration: subcutaneous
Placebo Comparator: placebo Run-in period (week -1 to 0): 10 µg volume-matched placebo ( 0.10 mL injection) once a day in the morning within 1 hour prior to breakfast Titration period (week 0 to 2): 10 µg volume-matched placebo (0.10 mL injection) once a day in the morning within 1 hour prior to breakfast Maintenance period (week 2 to 176): 20 µg volume-matched placebo (0.20 mL injection) once a day in the morning within 1 hour prior to breakfast	Drug: placebo Pharmaceutical form:sterile aqueous solution Route of administration: subcutaneous

Arms

Assigned Interventions

Experimental: Lixisenatide

Titration period (week 0 to 2): 10 µg lixisenatide (0.10 mL injection) once a day in the morning within 1 hour prior to breakfast Maintenance period (week 2 to 176): 20 µg lixisenatide (0.20 mL injection) once a day in the morning within 1 hour prior to breakfast

Drug: lixisenatide (AVE0010)

Pharmaceutical form:sterile aqueous solution

Route of administration: subcutaneous

Placebo Comparator: placebo

Run-in period (week -1 to 0): 10 µg volume-matched placebo ( 0.10 mL injection) once a day in the morning within 1 hour prior to breakfast Titration period (week 0 to 2): 10 µg volume-matched placebo (0.10 mL injection) once a day in the morning within 1 hour prior to breakfast Maintenance period (week 2 to 176): 20 µg volume-matched placebo (0.20 mL injection) once a day in the morning within 1 hour prior to breakfast

Drug: placebo

Pharmaceutical form:sterile aqueous solution

Route of administration: subcutaneous

Detailed Description:

The estimated maximum study duration for the first randomized patient will be approximately 204 weeks (± 14 days), with a median follow-up over all patients 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 patients will be followed from randomization until the end of study, which should occur when the last randomized patient has been followed for approximately 10 months. The actual end date of the study will be "event driven"and the study will end when there are approximately 844 positively-adjudicated primary cardiovascular outcome events.

Eligibility

Ages Eligible for Study:	30 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Men and women who experienced a spontaneous acute coronary syndrome (ACS) event [i.e., ST-segment elevation myocardial infarction (STEMI)] or non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (USA)] with a documented elevation above the normal reference range of a cardiac biomarker (Troponin or CK-MB) and the clinical presentation consistent with an acute coronary syndrome which leads to admission to an acute care facility, within 180 days following the ACS event and prior to screening.
Patients with a history of type 2 diabetes (for patients newly diagnosed, diagnosis will be 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.
HbA1c <5.5 % or >11% measured at screening visit.
Required to use incretin-based agents (eg, GLP-1 agonists or DPP-4 inhibitors) other than the study drug during the doubleblind treatment period.
Patients who have undergone CABG surgery following the qualifying ACS event.
Patients who have undergone PCI within 15 days prior to screening.
Patients 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 (eg, 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 patient's potential participation in a clinical trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147250

Contacts

Contact: For site information, send an email with site number to

Contact-Us@sanofi-aventis.com

Show 765 Study Locations

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

Clinical Sciences & Operations

Sanofi-Aventis

More Information

No publications provided

Responsible Party:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT01147250 History of Changes
Other Study ID Numbers:	EFC11319, 2009-012852-26, U1111-1116-5558
Study First Received:	June 17, 2010
Last Updated:	May 14, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris

Vascular Diseases
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on May 24, 2012