E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal persistent or permanent non-valvular atrial fibrillation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
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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 evaluate safety and tolerability of long-term treatment with AZD0837 compared to Vitamin-K antagonist (VKA) in non-valvular atrial fibrillation patients (AF) with a moderate to high risk of stroke and systemic embolic events. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetics of AZD0837 and its metabolites with special regard to the variability.
To evaluate the effect of AZD0837 on d-dimer levels compared to VKA in AF patients with a moderate to high risk of stroke and systemic embolic events.
To evaluate the effect of AZD0837 on Activated Partial Thromboplastin Time (APTT) and Ecarin coagulation time (ECT) in patients with AF and a moderate to high risk of stroke and systemic embolic events.
Exploratory: To explore anticoagulation-related quality of life and satisfaction among patients given AZD0837 compared to patients given VKA agents using the Duke Anticoagulation Satisfaction Scale (DASS). To explore general treatment satisfaction with AZD0837 compared to VKA agents using the Treatment Satisfaction Questionnaire for Medication (TSQM) including effectiveness, side effects, convenience and global satisfaction
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Provision of informed consent
Patients who fulfilled the inclusion criteria in study D1250C00008 and completed the planned study treatment period in study D1250C00008 without safety concerns regarding continued treatment, as assessed by the investigator
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E.4 | Principal exclusion criteria |
Aged <18 years at inclusion
Weight <40 kg at enrolment
Childbearing potential, ie women must be either post-menopausal a, permanently sterilized or, if of childbearing potential, must have a negative pregnancy test prior to initiation of study drug and use a reliable form of contraception b before and during the participation in the study. Women must not be breast feeding a Post menopausal patients are defined as patients with natural or induced menopause with last menstruation >1 year ago or bilateral oophorectomy b Reliable form of contraception is defined as: oral contraceptive, implant, long term injectable contraceptive, intrauterine device or tubal ligation. However, female patients using hormonal anti-conception method (oral, transdermal, vaginal ring or combination injectables) must agree to use an additional barrier method for contraception (condom or diaphragm)
AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
Known contraindication to VKA treatment
Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
Myocardial infarction, heart surgery (eg coronary artery bypass graft, CABG) or percutaneous transluminal coronary angioplasty (PTCA) within the previous three months prior to inclusion
Stroke and/or systemic embolism within the previous 30 days prior to inclusion
Conditions associated with increased risk of major bleeding for example: - history of intracranial bleeding - history of bleeding gastrointestinal disorder and/or endoscopically verified ulcer disease within the last year prior to inclusion - major surgical procedure or trauma two weeks prior to inclusion
Diastolic blood pressure (DBP) >100 mmHg or systolic blood pressure (SBP) >180 mmHg with or without antihypertensive treatment
Renal impairment (calculated creatinine clearance <30 ml/min) at the time of enrolment
Known hepatic disease and/or ALAT >3xULN at enrolment
History or presence of Human Immunodeficiency Virus (HIV) or infectious hepatitis including known HbSAg positive or antibodies against Hepatitis C
Known Gilberts syndrome
Anaemia (Hb<100 g/L = 6.2 mmol/L)
Platelet count <100 x 109/L
Treatment with antiplatelet other than ASA ≤100 mg/day or fibrinolytic agents within 10 days before inclusion
Planned (at the time of enrolment) cardioversion or surgery during the study
Other serious disease that give a calculated survival less than 12 months or any condition making a patient too frail to participate in the study
Known drug addiction and/or alcohol abuse
Inability to complete the study according to the protocol
Previous enrolment or inclusion of treatment in the present study. Participating in any other clinical study, except study D1250C00008, within 4 weeks (in UK within 12 weeks) prior to enrolment
Treatment with AZD0837 in previous or ongoing AZD0837 study, except study D1250C00008
Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome variables: - Safety AE (including bleedings) laboratory safety values physical examination electrocardiogram (ECG) vital signs (Blood pressure (BP) and pulse)
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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 | 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 | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
AZD0837 doses will be blinded to patient and investigator in the first part of the study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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.8.6 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 | Yes |
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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End of trial is defined as the date of database lock. After this time, no patient will be expose to study-related activities. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |