E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 5 |