E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 10002383 |
E.1.2 | Term | Angina pectoris |
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 demonstrate that over a 6-week treatment period ivabradine is more efficacious than placebo when given in combination with calcium antagonists (amlodipine or nifedipine) in patients with stable chronic effort angina pectoris. |
|
E.2.2 | Secondary objectives of the trial |
- To demonstrate the superiority of ivabradine versus placebo when given in combination with calcium antagonists (amlodipine or nifedipine) on the change of ETT criteria at the trough and at the peak of ivabradine activity over a 6-week treatment period and on the change in the mean number of angina attacks per week,
- To compare the change in the mean consumption of short acting nitrate per week between ivabradine and placebo when given in combination with calcium antagonists (amlodipine or nifedipine) over a 6-week treatment period,
- To assess the change of HR and RPP over a 6-week treatment period of ivabradine versus placebo when given in combination with calcium antagonists (amlodipine or nifedipine) at the trough and at the peak of ivabradine activity,
- To compare the safety and tolerability profile of ivabradine to placebo when given in combination with calcium antagonists (amlodipine or nifedipine) over a 6-week treatment period. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female aged >= 18 years,
- History of chronic stable angina pectoris,
- Normal sinus rythm,
- Patients having been treated by amlodipine or nifedipine for at least 4 weeks before selection,
- Patients with documented coronary artery disease (CAD). |
|
E.4 | Principal exclusion criteria |
- Recent acute myocardial infarction, coronary bypass surgery or percutaneous coronary intervention,
- Resting angina, unstable angina, Prinzmetal angina or microvascular angina,
- Patient with a pacemaker or implanted cardioverter-defibrillator,
- Patient who cannot perform exercise tests,
- Congestive heart failure stage III or IV NYHA, uncontrolled heart failure,
- HR < 60 bpm measured on ECG at rest at selection. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The response to treatment, evaluated over a 6-week treatment period and defined as a decrease of at least 3 angina attacks per week and/or an increase in the time to 1 mm ST segment depression of at least 60 s during a treadmill exercise tolerance test (ETT). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
evaluated over a 6-week treatment period |
|
E.5.2 | Secondary end point(s) |
Changes in other classical exercise tolerance test parameters (secondary efficacy criteria):
1. Change over a 6-week treatment period in all the ETT criteria (TED, TST 1mm, TAO, TLA, HR and RPP) at trough (i.e. 12 +/- 1 hours post dosing) and at peak (i.e. 3 +/- 1 hours postdosing) of ivabradine activity
2. Response to TST 1mm criterion defined as an increase over a 6 week treatment period in the time to 1 mm ST segment depression of at least 60 sec. at the trough of inabradine activity (i.e.12 +/- 1 hours post dosing) and 24+/-2 hours after amlodipine or nifedipine on centrally read values.
Response to angina attack criterion defined as a decrease of at least 3 angina attacks per week over a 6-week treatment period.
4. Clinical evolution of anginal disease (mean number of angina attacks per week, mean short acting nitrates consumption per week over a 6-week treatment period) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
evaluated over a 6-week treatment period |
|
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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 | Information not present in EudraCT |
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 |
Armenia |
Brazil |
Bulgaria |
Chile |
Estonia |
Hungary |
India |
Korea, Republic of |
Latvia |
Lithuania |
Mexico |
Moldova, Republic of |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
Tunisia |
Ukraine |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
Last visit last patient as stated in the protocol |
|
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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |