Atrial fibrillation clinically indicated for cardioversion. MedDRA version: 9.1 Level: LLT Classification code 10003658 Term: Atrial fibrillation
Conditions
Sponsors
AstraZeneca AB, European Regulatory Affairs
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent 2. Male or postmenopausal* female patients, age 20-80 years, inclusive 3. Clinical indication for cardioversion of AF 4. Current episode of AF lasting between 3 hours and 3 months at randomisation. Adequate anticoagulation according to international guidelines (ACC/AHA/ESC, 2006)** or national guidelines * Female patients will be considered postmenopausal if they fulfil criterion a) or b), and if age 1 year ago b) Induced menopause with last menstruation >1 year ago, due to: - Bilateral oophorectomy and/or hysterectomy - Radiation induced oophorectomy - Chemotherapy induced menopause c) Serum Follicle stimulating hormone (FSH), Luteinizing hormone (LH) and/or plasma oestradiol levels in the postmenopausal range as defined by the laboratory ** Fuster et al 2006: Circulation 2006;114:e257-e354 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: 1. Significant clinical illness or surgical procedure within 4 weeks preceding the enrolment visit or within the enrolment period as judged by the Investigator 2. Planned surgical procedure, including percutaneous coronary intervention (PCI), during the study (until the follow-up visit) 3. Estimated glomerular filtration rate (according to the Cockcroft-Gault formula) (GFR) 3xULN 4. Uncontrolled hyperthyroidism or hypothyroidism as judged by the Investigator 5. Blood Haemoglobin (Hb) 180 mmHg 11. Patients with CHF in NYHA class III or IV 12. LVEF 14 mm) 13. History and/or signs of clinically significant sinus and/or AV nodal dysfunction. Bradycardia (30 s) monomorphic ventricular tachycardia 17. QTcF interval >440 ms (the mean heart rate should preferably be 50 to 100 bpm. The QTcF should be calculated at AF as the mean of at least 5 consecutive RR intervals with consecutive QT intervals). 18. Complete bundle branch block (BBB), or any QRS duration =120 ms 19. Use of any antiarrhythmic drug class I or III, QT prolonging drug and/or drug that are strong or moderate inhibitor of CYP3A4 (except for verapamil), as well as St John’s Wort within five half-lives before randomisation (for amiodarone within the 3 months before enrolment) 20. Administration of an investigational drug within the preceding 3 months before randomisation 21. Administration of AZD1305 at any time before randomisation 22. History of drug addiction or alcohol abuse 23. Clinical judgement by the Investigator that the patient should not participate in the study 24. Blood or plasma donation within the preceding 12 weeks before enrolment into the study 25. A suspect or manifest infection according to IATA risk categories A and B 26. Involvement in the planning or conduct of the study (applies to both AstraZeneca staff and staff at the study site) Exclusion from the genetic research may be for any of the exclusion criteria specified in the main study or any of the following: -Previous bone marrow transplant -Received blood transfusion in the 120 days preceding the date of genetic sampling collection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary safety objective: To evaluate the dose-response relationship for QT effects of AZD1305 Primary efficacy objective: To demonstrate a dose-response relationship for AZD1305 given intravenously for conversion of AF to SR, and a statistically significant pair-wise difference for at least one of the dose levels of AZD1305 versus placebo ;Secondary Objective: Investigate the safety and tolerability of diff doses of AZD1305 compared to placebo Compare the proportion of patients with early relapse between diff doses of AZD1305 vs placebo Compare the proportion of patients remaining in SR up to 24 h and up to 13-18 d between diff doses of AZD1305 vs placebo Study the relationship between systemic exposure and response, with special regards to conversion of AF to SR and the effect on the QTcF interval Evaluate the predictability of AZD1305 pharmacokinetics including influence of co-variables Study the importance of co-variables, with respect to efficacy and safety of AZD1305 Evaluate the proportion of patients, who could be discharged within 6 hours (QTcF =500 ms) after start of infusion Additional exploratory objective (optional) - to collect and store DNA samples for potential future expl. genetic research related to: PK, efficacy, safety and tolerability responses to AZD1305; Susceptibility to and prognosis of CV disease;Primary end point(s): - Hearth rhythm (which primarily will be evaluated as the proportion of patients that converted from AF to SR within 90 minutes from start of infusion. Conversion has occurred if SR is maintained for at least 1 minute) - QTcF interval | — |
Countries
Czech Republic, Denmark, Hungary, Netherlands, Sweden
Outcome results
None listed