AZD1305 is a novel antiarrhythmic agent being developed for treatment of atrial fibrillation (AF). Potential indications include conversion of AF to sinus rhythm (SR) and maintenance of SR after conversion of AF. The main purpose of this study is to provide proof that AZD1305 prolongs atrial refractoriness in patients with atrial flutter, who are scheduled for a clinically indicated catheter ablation intended to bring cure to their atrial flutter
Conditions
Interventions
Product Code: AZD1305 (AR-H055767)
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intraven
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written Informed Consent 2. Patients with atrial flutter (with a ventricular rate of 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 FSH, LH and plasma oestradiol levels in the postmenopausal range 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. QTc (Fridericia, QTcF) >450 ms measured in sinus rhythm at randomisation 2. Serum potassium below 3.8 or above 5.0 mmol/L or plasma potassium below 3.6 or above 5.0 mmol/L (confirmed within 24 h prior administration of the investigational product) 3. QRS duration >120 ms at randomisation 4. AV-block I (prolonged PQ (PR) interval defined as >220 ms), AV-block II, AV-block III at randomisation 5. Left ventricular ejection fraction (LVEF) 180 mmHg, or diastolic BP >105 mmHg at randomisation 7. Congestive heart failure New York Heart Association (NYHA) class III or IV 8. Glomerular filtration rate (GFR) calculated according to the Cockcroft-Gault formula 13 mm) 13. Known preexcitation with Wolff-Parkinson-White (WPW) syndrome or without arrhythmias 14. Personal or family history of Torsades de Pointes (TdP), any other polymorphic ventricular tachycardia (PVT), sustained ventricular tachycardia, long QT syndrome and/or Brugada syndrome 15. Use of any QT prolonging drugs within five half-lives before administration of investigational product 16. Need for general anaesthesia or DC cardioversion during the ablation procedure 17. Clinically significant deviation in physical findings or laboratory values as judged by the Investigator 18. Significant clinical illness or surgical procedure within 4 weeks preceding the pre-entry visit 19. History of significant mental, renal or hepatic disorder, or other significant disease as judged by the Investigator 20. History of severe allergic disease 21. C-Reactive Protein (CRP) level >15 mg/L 22. Uncontrolled hyperthyroidism/hypothyroidism as judged by the Investigator 23. Blood haemoglobin <100 g/L at randomisation 24. Clinical judgement by the Investigator that the patient should not participate in the study 25. Inability to complete the study according to the Clinical Study Protocol 26. History of drug addiction and/or alcohol abuse 27. Blood or plasma donation within the preceding 12 weeks before administration of investigational product 28. Intake of an investigational product within the preceding 3 months before the administration of the investigational products in this study 29. A suspect or manifest infection according to WHO risk categories 2, 3 and 4 30. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the investigational site).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effects of AZD1305, compared to placebo, on the left atrial effective refractory period (LAERP), in patients undergoing an invasive electrophysiological procedure (EP).;Secondary Objective: 1) Evaluate the effects of AZD1305, compared to placebo, on the right atrial effective refractory period (RAERP) in patients undergoing an invasive EP 2) Evaluate the effects of AZD1305, compared to placebo, on the ventricular effective refractory period (VERP) and other electrophysiological and electrocardiographic variables in patients undergoing an invasive EP 3) Investigate the effects of AZD1305, compared to placebo, on haemodynamic variables in patients undergoing an invasive EP 4) Study the pharmacokinetic-pharmacodynamic relationship between plasma concentration of AZD1305 and QT /QTcF and if data is sufficient LAERP, RAERP and VERP 5) Investigate the safety and tolerability of AZD1305 compared to placebo in this patient population 6) Describe the pharmacokinetics of AZD1305 in this patient population 7) Collect and store DNA samples for potential future exploratory research into genes, which may influence drug response of AZD1305.;Primary end point(s): Left atrial effective refractory period (LAERP) | — |
Countries
Denmark, Finland, Sweden
Outcome results
None listed