A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 1,084
- 主要终点
- Creatinine
研究概览
简要总结
The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
- •Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
- •Previous systemic embolism.
- •Symptomatic congestive heart failure (CHF)
- •Impaired left ventricular systolic function
- •Diabetes mellitus
- •Hypertension requiring anti-hypertensive treatment.
排除标准
- •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
- •Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization
研究组 & 干预措施
1
AZD0837 450 mg
干预措施: AZD0837 (Drug)
2
AZD0837 200 mg
干预措施: AZD0837 (Drug)
3
AZD0837 300 mg
干预措施: AZD0837 (Drug)
4
AZD0837 150 mg
干预措施: AZD0837 (Drug)
5
Vitamin-K antagonist at INR 2-3
干预措施: Vitamin-K antagonist at INR 2-3 (Drug)
结局指标
主要结局
Creatinine
时间窗: 12 weeks according to protocol.(baseline to week 12 visit)
Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Bleeding Events
时间窗: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once
Alanine Aminotransferase (ALAT)
时间窗: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Number of patients while on study drug with ALAT\>=3 times upper limit of normal.l
Bilirubin
时间窗: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)
Number of patients while on study drug with Bilirubin\>=2 times upper limit of normal
次要结局
- Ecarin Clotting Time (ECT)(12 weeks according to protocol.(baseline to week 12 visit))
- Plasma Concentration of AZD0837 (Prodrug)(12 weeks after baseline according to protocol)
- Plasma Concentration of AR-H067637XX (Active Metabolite)(12 weeks after baseline according to protocol)
- Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT(36 weeks according to protocol)
- Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC(36 weeks according to protocol)
- Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC(36 weeks according to protocol)
- Activated Partial Thromboplastin Time (APTT)(12 weeks according to protocol.(baseline to week 12 visit))
- D-Dimer(14 weeks according to protocol.(enrolment to week 12 visit))