Excercise angina in patients with Coronary Artery Disease MedDRA version: 14.0 Level: LLT Classification code 10014292 Term: Effort angina System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Ranexa
Product Name: Ranexa
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Trade Name: Ranexa
Product Name: Ranexa
Sponsors
Menarini International Operations Luxembourg SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female patients (females of childbearing potential must be using adequate contraceptive precautions such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner). • Patients aged = 18 years. • Patients with coronary artery disease confirmed by angiography, prior MI, prior revascularization (PCI, CABG) and with exercise angina not controlled by the standard therapy. • ST-segment depression = 1mm during exercise ECG. • Capacity to perform the exercise test. • Able and willing to sign informed consent and to comply with study procedures. • Written informed consent prior to enrolment into the study. • Females of childbearing potential or within two years from the menopause must have a negative urine pregnancy test Inclusion criterion at visit 1 • Reproducible ST-segment depression = 1mm during two exercise tests performed 1 week apart (difference in exercise no more than 20%). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Angina at rest. • ECG abnormalities at rest (left bundle-branch block, resting ST-segment depression = 1mm, tachyarrhythmia). • Presence of factors that preclude satisfactory interpretation of the ECG (e.g. resting ST-segment depression = 1mm in any lead, left bundle-branch block, digoxin therapy) or repolarisation and conduction abnormalities. • Heart failure (class III or IV NYHA). • Moderate-severe hypertension (SBP>160 mmHg and/or DBP>100 mmHg). • Hypotension. • Acute coronary syndrome or coronary revascularization procedure within the prior 3 months before enrolment. • Females who are pregnant or nursing. • Any clinically relevant haematological or biochemical abnormality on routine screening, according to Investigator’s judgment. • Severe concurrent pathology, including terminal illness (cancer, AIDS, etc.). • Renal impairment defined as creatinine clearance 3 times greater than normal upper limit or total serum bilirubin > 1.5 times greater than normal upper limit • Pre-existing QT prolongation (including congenital long QT syndrome, uncorrected hypokalemia). • Patients on QT-prolonging drugs such as Class Ia (e.g., quinidine) and Class III (e.g., dofetilide, sotalol, dronedarone) antiarrhythmics, and antipsychotics (e.g., thioridazine, ziprasidone). • Existing contraindications for exercise testing (e.g. acute myocarditis or pericarditis, DVT, severe aortic stenosis) • Dementia, psychosis, alcoholism (>350 g ethanol/week) or chronic abuse of medicines, drugs or psychoactive substances. • Conditions which in the Investigator’s opinion may interfere with the study’s execution or due to which the patient should not participate for safety reasons. • Risk of low patient cooperation. • Inability or unwillingness to issue the informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Change in treadmill total exercise duration with ranolazine or placebo at peak ranolazine plasma levels (4 hrs after dosing) ;Timepoint(s) of evaluation of this end point: After 24 weeks of full-dose treatment.;Main Objective: The primary study objective will be to verify whether ranolazine 750 mg b.i.d. is effective in increasing exercise capacity (exercise treadmill time at peak).;Secondary Objective: The secondary study objectives will be to verify whether ranolazine is effective in reducing angina frequency and nitroglycerin consumption/week. The assessment of safety by evaluation of adverse events, laboratory findings and physical examination will also be considered a secondary study objective. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: If not specified has to be intended at each visit when the parameter is assessed;Secondary end point(s): - Change in treadmill total exercise duration with ranolazine or placebo at peak ranolazine plasma levels (4 hrs after dosing) after 4 (Visit 6) and 12 (Visit 7) weeks of full-dose treatment. - Change in time to 1 mm ST-segment depression at peak ranolazine plasma levels. - Change in time to angina at peak ranolazine plasma levels. - Number of angina attacks/week. - Number of sublingual nitroglycerin consumption/week. | — |
Countries
Austria, Bulgaria, Germany, Greece, Ireland, Italy, Spain, Switzerland, United Kingdom
Contacts
Public ContactStudy Medical Expert (SME)
Menarini International Operations Luxembourg SA
Outcome results
None listed