A single-centre, single-blind, randomised, placebo-controlled phase IIa study to investigate the effect of AZD1305 given as an iv infusion on left ventricular performance in patients with left ventricular dysfunctio

• Conditions: eft ventricular function in patient with left ventricular dysfunction.

• Registration Number: EUCTR2008-001254-41-SE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-15
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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.

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.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 AZD130

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To explore if AZD1305 compromises left ventricular function in patients with left ventricular dysfunction.;Secondary Objective: To evaluate the tolerability and safety of AZD1305 given as an intravenous (iv) infusion to patients with left ventricular dysfunction.<br><br>To evaluate the pharmacokinetics of AZD1305, given as an iv infusion, in patients with left ventricular dysfunction.<br><br>To exploratively evaluate the relationship between dose, plasma concentration and QTcF interval, QRS duration and, if possible, left ventricular function.<br><br>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. <br>;Primary end point(s):