E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Left ventricular function in patient with left ventricular dysfunction. |
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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 |
To explore if AZD1305 compromises left ventricular function in patients with left ventricular dysfunction. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the tolerability and safety of AZD1305 given as an intravenous (iv) infusion to patients with left ventricular dysfunction.
To evaluate the pharmacokinetics of AZD1305, given as an iv infusion, in patients with left ventricular dysfunction.
To exploratively evaluate the relationship between dose, plasma concentration and QTcF interval, QRS duration and, if possible, left ventricular function.
To collect and store DNA samples (from all randomised patients who give additional informed consent) for potential future exploratory research into genes which may influence drug response of AZD1305.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent 2. Male patients and postmenopausal women aged 20-80 years 3. LVEF 30- 45% on echocardiography.Patients with an ejection fraction >45% can be included if he/she has a well documented diagnosis of cardiac failure/cardiomyopathy with a previous EF below 45% and is judged to have normal ejection fraction due to optimised medical treatment. 4. In SR without diagnosis of AF during the dosing days. 5. No significant changes in the medication for heart failure, during the preceding 1 month before enrolment (e.g. ACE inhibitors, AT1 blockers, beta-receptor blockers and/or aldosterone antagonists, diuretics) as judged by the investigator 6. deleted 7. Provision of written informed consent for genetic research (optional). 1. Women will be considered postmenopausal if they fulfil criterion a) and/or b), and criterion c): a) Natural menopause with last menstruation >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/or plasma oestradiol levels in the postmenopausal range as defined by the laboratory.
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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. Severe or clinically unstable heart failure (NYHA III-IV) 3. Haemodynamically unstable condition as judged by the investigator, systolic blood pressure (BP) <100 mmHg or >180 mmHg, or diastolic BP >105 mmHg at enrolment 4. AV-block I (prolonged PQ (PR) interval defined as >220 ms), AV-block II, AV-block III, bundle branch block (BBB) 5. QRS duration >120 ms at randomization 6. QTcF interval >450 ms measured at randomization 7. Any of the following events, or any other significant cardiovascular event as judged by the investigator, during the last 3 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) or coronary artery bypass grafting (CABG)) 8. Significant clinical illness or surgical procedure within 4 weeks preceding the pre-entry visit 9. 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 10. History of past or ongoing severe allergic disease, significant mental, renal or hepatic disorder, or other significant disease as judged by the investigator 11. Known preexcitation 12. History and/or signs of clinically significant sinus node dysfunction, or sinus rhythm with a heart rate (HR) below 45 or above 100 beats per minute 13. Pacemaker or Implantable Cardioverter Defibrillator (ICD) therapy 14. Significant aortic stenosis or hypertrophic obstructive cardiomyopathy 15. C-Reactive Protein (CRP) >15 mg/L 16. Potassium in serum or plasma below 3.8 or above 5.3 mmol/L 17. Blood Haemoglobin (Hb) <100 g/L at randomisation 18. Glomerular filtration rate (GFR) calculated according to the Cockcroft-Gault formula1 <30 mL/min 1.Estimated glomerular filtration rate (GFR) for men and women as follows: 1.Estimated glomerular filtration rate (GFR) for men and women as follows: Creatinine Clearance men=1.23 x (140 - age (years) x weight (kg)/serum creatinine (µmol/l) Creatinine Clearance women=1.04 x (140 - age (years) x weight (kg)/(serum creatinine (µmol/l) 19. Intake of “over-the-counter”-drugs, including herbals, such as St John’s worth (within 3 weeks), vitamins, minerals and also grapefruit (including grapefruit juice) within one week before the first administration of AZD1305 20. Use of any antiarrhythmic drug (e.g. class I and/or III, sotalol, digitalis glycoside, verapamil and amiodarone) 21. Use of QT prolonging drug and/or drug that inhibits CYP3A4, as well as St John’s Worth within five half-lives before administration of AZD1305 22. History of drug addiction and/or alcohol abuse and/or positive drug screen 23. Clinical judgement by the investigator that the patient should not participate in the study 24. A suspect or manifest infection according to IATA risk categories A and B 25. Regular use of nicotine (smoking, snuff, nicotine chewing gum or nicotine plaster) daily (average of >7 cigarettes or snuff portions per week) 26. Blood or plasma donation within the preceding 12 weeks before the administration of AZD1305 or other investigational product 27. Intake of an investigational drug within the preceding 3 months before the first administration of AZD1305 28. Intake of AZD7009 (predecessor of AZD1305) and/or AZD1305 at any time before administration of investigational product 29. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 30. Previous randomization of treatment in the present study.
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of the study is defined as the "last visit of the last patient 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 | 9 |
E.8.9.1 | In the Member State concerned days | |