stable angina pectoris MedDRA version: 7.0 Level: PT Classification code 10002383
Conditions
Interventions
Product Name: Ivabradine
Product Code: S16257-F42
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ivabradine
CAS Number: 155974-00-8
Current Sponsor code: S16257-02
Concentration unit: mg
Sponsors
Institut de Recherches Internationales Servier
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients to be selected will be male or female outpatients between 18 (or the legal age) and 75 years with a history of stable angina pectoris (duration >or= 3 months) with no angina at rest and no angina of class IV of the Canadian Cardiovascular Society classification, treated by atenolol 50 mg o.d. or by any other beta-blocker at equivalent dosage (duration of treatment >or= 3 months) and who still present a positive ETT or symptomatic angina in everyday life. Heart rate (ECG) at rest with atenolol (50 mg o.d.) must be >or= 60 bpm at pre-selection and inclusion. Patients to be included should have three positive exercise tolerance tests (limiting angina pain + ST depression >or= 1 mm within 3 min to 12 min) and stable exercise tolerance test (time to 1 mm ST segment depressions between second selection visit and inclusion visit ETT must be within ± 20% or ±1 min of each other) during the run-in period. 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: - Modification of a selection criteria that would prevent the patient of being included. - Any clinical deterioration during the run-in period, as demonstrated by a significant increase in the mean number of anginal attacks per week and by a significant increase in the mean nitrates consumption per week (increase by more than 5 in the mean number of angina attacks per week and by more than 50% respectively between SEL1 and M0 visits). - HR 130%. - Patient having stopped the ETT preceding inclusion before reaching the positivity criteria for one of the reasons listed in appendix 4 as criteria for early interruption of the exercise test. - Non stability in ST segment depression. - Abnormalities in the laboratory blood tests performed at SEL2 considered to be dangerous for the patient if he/she continued in the study: - severe renal failure (serum creatinine > 200 micromoles per litre), - severe liver function test abnormalities: ALAT or ASAT > 3 times the upper normal values, - electrolyte disorders, particularly kaliema 5.2 mmol/l, - significant anaemia defined as blood haemoglobin lower than 110 grams per litre (in males) or lower than 100 grams per litre (in females).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that after a 4-month treatment period ivabradine (5 mg b.i.d. given orally for 2 months then 7.5 mg b.i.d. given orally for other 2 months) is more efficacious than placebo when given in combination with atenolol alone (50 mg o.d.) in patients with stable chronic effort angina pectoris previously treated by atenolol 50 mg o.d. (or another beta-blocker at a dosage equivalent to 50 mg of atenolol o.d.). ;Secondary Objective: - To demonstrate the superiority of ivabradine (5 mg b.i.d. then 7.5 mg b.i.d. given orally for 2 months each) versus placebo when given in combination with atenolol (50 mg o.d.) on the other ETT criteria over a 4-month period and on all ETT criteria over a 2-month period. - To compare the safety and tolerance profile of ivabradine (5 mg then 7.5 mg b.i.d.) to placebo when given in combination with atenolol.;Primary end point(s): The primary efficacy criterion will be the change from baseline over a 4-month treatment period in the total exercise duration on a treadmill exercise tolerance test (ETT) according to the standard Bruce protocol at the trough of ivabradine and atenolol activity (i.e. 12±1 hours and 24±2 hours post-dosing respectively) on centralised reading values. | — |
Countries
Germany, Hungary, Italy, Norway, Spain, Sweden, United Kingdom
Outcome results
None listed