Paroxysmal, persistent or permanent nonvalvular atrial fibrillation MedDRA version: 8.1 Level: LLT Classification code 10003658 Term: Atrial fibrillation
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed informed consent given by the patient before any study-specific procedures are initiated. Paroxysmal, persistent or permanent nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week; for: Patients not on VKA treatment: the second ECG should be carried out within the 2 weeks prior to randomization. VKA treated patients: the second ECG should be carried out within the 12 weeks prior to randomization. In addition to AF the patient must have one or more risk factors according to the following: Either one of the following risk factors (high risk patient): - Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization) - Previous systemic embolism or at least one of the following risk factors (1 risk factor = moderate risk patient, 2 or more risk factors = high risk patient): - Age =75 years - Symptomatic congestive heart failure (CHF) - Impaired left ventricular systolic function - Diabetes mellitus - Hypertension requiring anti-hypertensive treatment (Hypertensive patients who are enrolled and randomized into the study should be well controlled and have antihypertensive treatment aiming for a blood pressure =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Aged 1 year ago or bilateral oophorectomy. b Reliable form of contraception is defined as: double-barrier method (condoms with spermicide, diaphragm with spermicide), 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 randomization Stroke or transient ischaemic attack (TIA) and/or systemic embolism within the previous 30 days prior to randomization 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 randomization - major surgical procedure or trauma two weeks prior to randomization Diastolic blood pressure (DBP) >100 mmHg or systolic blood pressure (SBP) >180 mmHg with or without antihypertensive treatment Renal impairment (calculated creatinine clearance 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 randomization Planned 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 randomization of treatment in the present study. Participating in any other clinical study within 4 weeks (in UK within 12 weeks) prior to enrolment Treatment with AZD0837 in previous or ongoing AZD0837 study(ies) Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To provide dose-guiding information through evaluation of safety and tolerability of four dosing regimens of AZD0837 in relation to Vitamin-K antagonist (VKA) treatment in atrial fibrillation (AF) patients with moderate to high risk of stroke.;Secondary Objective: To evaluate the pharmacokinetics (PK) of the active form of AZD0837 (AR H067637XX) with special regard to: - Evaluation of the influence of concomitant medications on the PK variables of AR H067637XX in plasma with special regards to estimated systemic exposure - Assessment of the relationship between systemic plasma exposure of AR H067637XX and clinical events (AEs) To evaluate the pharmacodynamic (PD) properties of AZD0837 in the patient population. To evaluate the influence of a genetic variant (C3435T) of the MDR1 gene, coding for the drug transporter P-glycoprotein (P-gp), on PK parameters of AZD0837 and/or its metabolites. To collect and store DNA, for future retrospective research into genes that may influence therapeutic response of AZD0837 and VKA. Appropriate informed consent will be obtained before genetic blood sampling. ;Primary end point(s): Primary outcome variables (safety): - Adverse events (AE), including bleedings - electrocardiogram - vital signs (blood pressure and pulse) - laboratory values - physical examination | — |
Countries
Austria, Denmark, Hungary, Ireland, Sweden, United Kingdom
Outcome results
None listed