NON-PERMANENT ATRIAL FIBRILLATION MedDRA version: 14.1 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: RANEXA 375 mg
Product Name: RANOLAZINE
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: RANOLAZINE
CAS Number: 95635-55-5
Other descriptive name: RANEXA 375
Concentration
Sponsors
Menarini Ricerche S.p.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients 18 years and older; 2. Patients with persistent AF suitable for electrical direct current cardioversion (DCC); NOTE: According to the ESC classification, persistent AF is defined as a continuous AF with a minimum duration of 7 days or requiring termination by cardioversion. Prior to randomisation, successful electrical cardioversion and maintenance of sinus rhythm at 2 hours shall be documented; 3. A female of childbearing potential may be enrolled providing she: - has a negative pregnancy test at baseline and - is routinely using an effective method of birth control resulting in a low failure rate (e.g.. hormonal contraception, intrauterine device, condoms in combination with a spermicidal cream, total sexual abstinence orsterilisation) until end of study which corresponds to the follow-up safety call, 2 weeks after end of treatment; 4. Able to give written informed consent before any study related procedure; 5. Able to attend all the visits scheduled in the study and able to independently record transtelephonic electrocardiograms (TT-ECGs) after being instructed by the Investigator. 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 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1. Patients with first diagnosed AF (namely first onset of AF irrespective of duration of arrhythmia or presence and severity of AF related symptoms) or patients with paroxysmal AF (namely self-terminating AF usually within 48 hours although it may continue for up to 7 days); 2. Patients with long-standing persistent AF (for this protocol defined as AF longer than 6 months) or permanent AF (i.e. AF accepted by the patient and by the physician); 3. Patients having known concurrent temporary secondary causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, pneumonia, hypoxemia, acute pericarditis or myocarditis; 4. Patients having undergone atrial catheter ablation for AF; 5. Patients carrying a pacemaker; 6. Patients with electrolytes imbalances that may cause cardiac arrhythmias, e.g. potassium 5.5 mmol/L; 7. Patients with severe renal impairment (creatinine clearance 2.5x upper limits of normal at screening or severe hepatic impairment of any kind; 9. Patients taking potent CYP3A4 inhibitors (e.g. Itraconazole, Ketoconazole, Voriconazol, Posaconazol, HIV protease inhibitors, Clarithromycin, Telithromycin, Nefazodone); 10. Patients taking CYP3A4 inducers (e.g. Rifampicin, Phenytoin, Phenobarbital, Carbamazepine, St. John's Wort); 11. Patients taking class I or Class III antiarrhythmic agents within 3 days of planned randomisation. NOTE: intravenous flecainide or propafenone are allowed up to 72 hours and 24 hours from the planned randomisation, respectively; 12. Patients taking beta-blockers unless used on stable doses for at least 2 weeks prior to the planned randomisation NOTE: Single doses of Intravenous beta-blockers are allowed up to 10 hours from the planned randomisation; 13. Patients taking Dronedarone or oral Amiodarone within 2 weeks and 3 months of planned randomisation, respectively. NOTE: Intravenous administration of Amiodarone is prohibited within 72 hours from planned randomisation; 14. Patients with a history of ECG abnormalities that in the opinion of the Investigator render the subject unsuitable for the trial, including history of congenital or a family history of long QT syndrome and a QTc interval =450 msec at Screening; 15. Patients with congestive heart failure NYHA grade III and IV; 16. Patients known to be hypersensitive to Ranolazine or to any of the components of the formulation; 17. Pregnant or breast feeding women; 18. Patients with any serious intercurrent illness (including psychiatric and neurological disorders) which, in the opinion of the Investigator, is incompatible with the protocol; 19. Abuse of alcohol (hazardous consumption defined as >30 g ethanol/day in men and >20 g/day in women), analgesics, or psychotropic drugs; 20. Patients concurrently participating in another study, or who have received an investigational drug within 30 days prior to screening; 21. Patients unable to communicate well with the Investigator and to comply with the requirements of the entire study. 22. Patients with known cytochrome CYP2D6 enzyme deficiency (poor metabolisers). 23. Patients taking Metformin at a total daily dose greater than 1000 mg. 24. Patients taking Simvastatin at a total daily dose greater than 20 mg daily.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Ranolazine administered as 3 different doses regimens (375, 500, 750 MG BID) versus placebo in the maintenance of sinus rhythm after electrical cardioversion in patients with nonpermanent AF (defined as a continuous AF with a minimum duration of 7 days to a maximum of 6 months or requiring termination by cardioversion);Secondary Objective: - To evaluate the dose-effect relationship of Ranolazine to support the choice of the dose to be studied in a subsequent phase III study. - To assess the safety of Ranolazine versus placebo after electrical cardioversion in patients with non permanent AF.;Primary end point(s): - Time (median [days]) from randomisation to the first documented AF recurrence. Documented recurrence is defined as AF detected on TTECGs by the Core Central Lab or on 12-Lead ECGs performed during a study visit (scheduled or unscheduled).;Timepoint(s) of evaluation of this end point: Max evaluation period of 4 months (112 days). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time (median [days]) from randomisation to first documented and confirmed AF recurrence. Confirmed AF recurrence is defined as a documented AF which is confirmed by a consecutive ECG performed at least 1 hour after its first documentation. - Time (median [days]) from randomisation to first documented AF recurrence in the subpopulation of patients who are still in sinus rhythm 2 days after the electrical cardioversion. - Dose-effect relationship comparing the time (median, days) from randomisation to first documented AF recurrence between Ranolazine doses.;Timepoint(s) of evaluation of this end point: Max evaluation period of 4 months (112 days). | — |
Countries
Germany, Italy, Spain, United Kingdom
Contacts
Public ContactClinical Research Corporate Directo
Menarini Ricerche S.p.A
Outcome results
None listed