The main purpose of this study is to investigate the feasibility to use a loading dose as a tool for identifying patients who may have an exaggerated QT response to AZD1305 and would therefore not be candidate for long term treatment.
Conditions
Interventions
Product Code: AZD1305 (AR-H055767)
Pharmaceutical Form: Prolonged-release tablet
Current Sponsor code: AZD1305
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent 2. Male subjects and postmenopausal women aged 20-80 years 3. Documented AF 4. SR, for a minimum of 2 hours and a maximum of 90 days, at randomisation 5. Effective oral anticoagulation according to international and/or national guidelines. In self-terminating AF with a duration of less than 48 hours, decision on anticoagulation should be made according to guidelines (Fuster et al 2006) For the optional genetic component of the study: 6. Provision of written informed consent for genetic research 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. Clinically significant deviation in physical findings or laboratory values as judged by the Investigator. 2. Significant clinical illness or surgical procedure within four weeks preceeding the pre-entry visit (Visit 1) 3. History of severe allergic disease, significant mental, renal or hepatic disorder, or other significant disease as judged by the Investigator 4. History of severe skin reactions due to use of electrodes 5. C-Reactive Protein (CRP) >15 mg/L 6. Estimated Creatinine clearance/glomerular filtration rate (GFR) according to the Cockcroft-Gault formula 180 mmHg, or diastolic BP >105 mmHg at randomisation 12. Congestive heart failure New York Heart Association (NYHA) class III or IV 13. Left ventricular ejection fraction (LVEF) 13 mm) 18. Pacemaker or Implantable Cardioverter Defibrillator (ICD) therapy 19. Known preexcitation 20. 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 21. QTc (Fridericia, QTcF ) interval >450 ms measured in SR at randomisation 22. QRS duration >120 ms at randomisation 23. AV-block I (prolonged PQ (PR) interval >220 ms), AV-block II, AV-block III, or complete bundle branch block (BBB) at randomisation 24. Serum potassium below 3.8 or above 5.3 mmol/L, or plasma potassium below 3.6 or above 5.3 mmol/L at randomisation 25. Use of any antiarrhythmic drug class I and/or III, digitalis glycoside, QT prolonging drug and/or drug that inhibits CYP3A4, as well as St John’s Worth within five half-lives before administration of AZD1305 or other IP (for amiodarone within the 3 months before enrolment). 26. Intake of an investigational drug within the preceeding 3 months before administration of AZD1305 or other IP 27. Intake of AZD7009 and/or AZD1305 at any time before administration of AZD1305 or other IP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to explore the relationship between QTcF at first dose (loading dose) and QTcF at steady state after treatment with AZD1305, in order to identify outliers with regards to QTcF response when given to patients with documented AF but presently in stable SR for at least 2 h and a maximum of 28 days.;Secondary Objective: The secondary objectives of the study are to: · investigate the safety and tolerability of AZD1305 compared to placebo · evaluate the Pharmacokinetics (PK) of AZD1305 with special regard to: - evaluation of the influence of concomitant medication and demographic variables on the PK variables of AZD1305 - assessment of the relationship between exposure of AZD1305 and QTcF · evaluate the use of trans telephonic monitoring (TTM) measured as patient compliance, number of unscheduled recordings and correlation between symptoms and rhythm collect blood samples for future DNA analysis in the optional genetic research part of the study ;Primary end point(s): The primary variable for this study is QTcF as measured by the Investigator following the loading dose, at Study Day 4, at Study Day 6 and at Study Day 10 | — |
Countries
Denmark, Slovakia, Sweden
Outcome results
None listed