A Randomised, Placebo-controlled, Double-blind, Parallel-group, Multicentre, Phase IIa Study to Explore the Relationship between QTcF Interval at First Dose (Loading Dose) and at Steady State after Treatment with AZD1305 Extended-release Tablets or Placebo when given to Patients with Documented AF

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

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

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 <30 mL/min
7.Uncontrolled hyperthyroidism or hypothyroidism as judged by the Investigator
8.Blood Haemoglobin (Hb) <100 g/L at randomisation
9.Ongoing AF or atrial flutter at randomisation
10.Any of the following events, or any other significant cardiovascular event as judged by the Investigator, during the last 6 months before randomisation: myocardial infarction, unstable angina pectoris or other signs of myocardial ischaemia, stroke or transient ischaemic attack (TIA), myocardial revascularisation (percutaneous coronary intervention (PCI)), coronary artery bypass graft (CABG), or other revascularisation procedure.
11.Haemodynamically unstable condition as judged by the Investigator, systolic BP <100 mmHg or >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) <40% on echocardiography, or other clinically significant abnormality on the echocardiogram (not older than 6 months) as judged by the Investigator
14.History and/or signs of clinically significant sinus and/or AV nodal dysfunction
15.Sinus bradycardia (<50 beats per minute (bpm)) at randomisation
16.Any clinically significant valvular heart disease
17.Hypertrophic cardiomyopathy or significant left ventricular hypertrophy (free wall or septal thickness >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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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