E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Patient Reported Outcomes
Date: 2 December 2010, Version 1
Objective: to assess the effect of Lixisenatide (vs. placebo) on overall and cardiovascular health of the patients as reported by patients in response to the questionnaires |
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E.3 | Principal 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.
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E.4 | Principal 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 (1 retest within a week of receipt of the result is permitted with the result of the last sample being decisive).
. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
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) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- 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 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
-Percent change in the urinary albumin/creatinine ratio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 0 to week 203 for secondary endpoints 1 and 2
from baseline to week 108 for secondary endpoint 3 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 298 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belarus |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Denmark |
Egypt |
Estonia |
Finland |
France |
Germany |
Guatemala |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Netherlands |
New Zealand |
Norway |
Panama |
Peru |
Philippines |
Poland |
Portugal |
Romania |
Russian Federation |
Serbia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Tunisia |
Turkey |
Ukraine |
United Arab Emirates |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last Visit Last Subject (LVLS) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 47 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 47 |