A Multi-centre, Double-blind, Randomised, Placebo-controlled, Single-dose, Phase II Study to Assess the Effects on Atrial and Ventricular Refractoriness and Haemodynamics of an Intravenous Infusion of AZD1305 in Patients Undergoing an Invasive Electrophysiological Procedure

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-003455-36-SE
• Date of registration: 07/11/2007
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A Multi-centre, Double-blind, Randomised, Placebo-controlled, Single-dose, Phase II Study to Assess the Effects on Atrial and Ventricular Refractoriness and Haemodynamics of an Intravenous Infusion of AZD1305 in Patients Undergoing an Invasive Electrophysiological Procedure
• Scientific title: A Multi-centre, Double-blind, Randomised, Placebo-controlled, Single-dose, Phase II Study to Assess the Effects on Atrial and Ventricular Refractoriness and Haemodynamics of an Intravenous Infusion of AZD1305 in Patients Undergoing an Invasive Electrophysiological Procedure
• Date of first enrolment: 12/12/2007
• Target sample size: 64
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003455-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Denmark, Finland, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of written Informed Consent

2. Patients with atrial flutter (with a ventricular rate of <100 beats/minute at enrolment), scheduled for curative catheter ablation with cryoablation or radiofrequency ablation

3. Sinus rhythm at randomisation

4. Male or postmenopausal* female, aged 20 to 80 years inclusive.

For the optional genetic component of the study:
5. Provision of specific written Informed Consent for genetic research.

*Postmenopausal patients are defined as women fulfilling at least one of the following criteria:
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 plasma oestradiol levels in the postmenopausal range


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. QTc (Fridericia, QTcF) >450 ms measured in sinus rhythm at randomisation

2. Serum potassium below 3.8 or above 5.0 mmol/L or plasma potassium below 3.6 or above 5.0 mmol/L (confirmed within 24 h prior administration of the investigational product)

3. QRS duration >120 ms at randomisation

4. AV-block I (prolonged PQ (PR) interval defined as >220 ms), AV-block II, AV-block III at randomisation

5. Left ventricular ejection fraction (LVEF) <40% on echocardiography, or other clinically significant abnormality on the echocardiogram as judged by the investigator (not older than 6 months)

6. Systolic blood pressure <100 mmHg or >180 mmHg, or diastolic BP >105 mmHg at randomisation

7. Congestive heart failure New York Heart Association (NYHA) class III or IV

8. Glomerular filtration rate (GFR) calculated according to the Cockcroft-Gault formula <30 mL/min)

9. Use of any antiarrhythmic drug class I and/or III and/or digitalis glucosides within five half-lives before administration of investigational product (for amiodarone within the preceding 3 months)

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. Any clinically significant valvular heart disease

12. Hypertrophic cardiomyopathy or significant left ventricular hypertrophy (free wall or septal thickness >13 mm)

13. Known preexcitation with Wolff-Parkinson-White (WPW) syndrome or without arrhythmias

14. 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

15. Use of any QT prolonging drugs within five half-lives before administration of investigational product

16. Need for general anaesthesia or DC cardioversion during the ablation procedure

17. Clinically significant deviation in physical findings or laboratory values as judged by the Investigator

18. Significant clinical illness or surgical procedure within 4 weeks preceding the pre-entry visit

19. History of significant mental, renal or hepatic disorder, or other significant disease as judged by the Investigator

20. History of severe allergic disease

21. C-Reactive Protein (CRP) level >15 mg/L

22. Uncontrolled hyperthyroidism/hypothyroidism as judged by the Investigator

23. Blood haemoglobin <100 g/L at randomisation

24. Clinical judgement by the Investigator that the patient should not participate in the study

25. Inability to complete the study according to the Clinical Study Protocol

26. History of drug addiction and/or alcohol abuse

27. Blood or plasma donation within the preceding 12 weeks before administration of investigational product

28. Intake of an investigational product within the preceding 3 months before the administration of the investigational products in this study

29. A suspect or manifest infection according to WHO risk categories 2, 3 and 4

30. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at the investigational site).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

AZD1305 is a novel antiarrhythmic agent being developed for treatment of atrial fibrillation (AF). Potential indications include conversion of AF to sinus rhythm (SR) and maintenance of SR after conversion of AF. The main purpose of this study is to provide proof that AZD1305 prolongs atrial refractoriness in patients with atrial flutter, who are scheduled for a clinically indicated catheter ablation intended to bring cure to their atrial flutter

Intervention(s)

Product Code: AZD1305 (AR-H055767)
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: 1) Evaluate the effects of AZD1305, compared to placebo, on the right atrial effective refractory period (RAERP) in patients undergoing an invasive EP

2) Evaluate the effects of AZD1305, compared to placebo, on the ventricular effective refractory period (VERP) and other electrophysiological and electrocardiographic variables in patients undergoing an invasive EP

3) Investigate the effects of AZD1305, compared to placebo, on haemodynamic variables in patients undergoing an invasive EP

4) Study the pharmacokinetic-pharmacodynamic relationship between plasma concentration of AZD1305 and QT /QTcF and if data is sufficient LAERP, RAERP and VERP

5) Investigate the safety and tolerability of AZD1305 compared to placebo in this patient population

6) Describe the pharmacokinetics of AZD1305 in this patient population

7) Collect and store DNA samples for potential future exploratory research into genes, which may influence drug response of AZD1305.

Primary end point(s): Left atrial effective refractory period (LAERP)

Main Objective: Evaluate the effects of AZD1305, compared to placebo, on the left atrial effective refractory period (LAERP), in patients undergoing an invasive electrophysiological procedure (EP).

Secondary ID(s)

2007-003455-36-FI

D3190C00005