E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes patients with a recent acute coronary syndrome (ACS) event
|
|
E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes patients with a recent acute coronary syndrome (ACS) event
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007649 |
E.1.2 | Term | Cardiovascular disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 determine whether aleglitazar reduces cardiovascular mortality and morbidity (defined as non-fatal myocardial infarction (MI) and non-fatal stroke) in patients with a recent ACS event and T2D |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effects of aleglitazar on other clinical endpoints of cardiovascular risk
• To evaluate the effects of aleglitazar on glycemic control, the lipoprotein profile, blood pressure, and biomarkers of cardiovascular risk.
• To evaluate the tolerability and long-term safety profile of aleglitazar (with special attention to known PPAR class adverse events such as fluid retention, heart failure, fractures, renal function, musculoskeletal adverse events and liver enzymes elevation). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females aged > 18 years
2. Known/established T2D or newly diagnosed T2D
(confirmed prior to randomization according to the
American Diabetes Association diagnostic criteria in Protocol Section 4.4)
3. Hospitalization for an ACS event (refer to definition in the protocol) and randomization between hospital discharge and 8 weeks after the ACS index event (day of hospitalization). In case of any subsequent ACS event, procedure related MI or coronary bypass surgery occurring during the run-in period, randomization should occur when the patient’s conditions are deemed stable by the investigator but no later than 8 weeks from this new event. However, for these patients, the maximum allowed duration from index event to randomization is 12 weeks.
4. Ability and willingness to give written informed consent
and to comply with the requirements of the study |
|
E.4 | Principal exclusion criteria |
1. Concomitant treatment with a thiazolidinedione and/or
fibrate
2. Prior intolerance to a thiazolidinedione and/or fibrate
3. Triglycerides (fasting) > 400 mg/dL (> 4.5 mmol/L)
4. Patients with clinically apparent liver disease, eg, jaundice, choleastasis, hepatic impairment, active hepatitis or asymptomatic ALT > 3x ULN
5. Anemia defined as hemoglobin < 10 g/dL (< 100 g/L, 6.21 mmol/L) or hematocrit < 30 %
6. eGFRMDRD < 45 ml/min/1.73m2
7. Symptomatic congestive heart failure classified as NYHA
class II-IV
8. Hospitalization in the 12-month period preceding the index event for a primary diagnosis of heart failure
9. Peripheral edema which in the judgment of the investigator is believed to be clinically severe
10. Systemic corticosteroid therapy for > 2 weeks, within 3
months prior to screening examination
11. Any serious medical condition that according to the
investigator could interfere with the conduct of the study
12. Serious comorbid disease in which the life expectancy of
the patient is shorter than the duration of the trial (e.g. acute systemic infection, cancer or other serious illnesses). Treated basal-cell carcinoma before randomization is not excluded
13. Unwillingness or inability to comply with study requirements (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency)
14. Positive pregnancy test, breast feeding women or women
of childbearing potential not using highly effective methods of contraception
15. Participation in any clinical trial with an investigational
drug or device within one month prior to the screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the time to first
occurrence of any component of the composite endpoint as
adjudicated by the Clinical Events Committee. Components of
the primary endpoint are:
- Cardiovascular death
- Non-fatal myocardial infarction
- Non-fatal stroke |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout study, approximately 4.5 years |
|
E.5.2 | Secondary end point(s) |
1. Glycemic control, lipoprotein profile, blood pressure, biomarkers of cardiovascular risk
2. Tolerability and long-term safety profile |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For 1: Throughout study, months 1, 3, 6, 9, 12 and then every 6 months thereafter
For 2: Throughout study, approximately 4.5 years |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 274 |
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 |
Australia |
Brazil |
Canada |
China |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
India |
Italy |
Malaysia |
New Zealand |
Poland |
Romania |
Russian Federation |
United States |
|
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
|
The end of the study is defined as the date of the last patient last visit, or the date at which the last data point, which is required for statistical analysis (i.e. key safety and efficacy results for decision making), is received, whichever is the later date. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |