| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-valvular Atrial Fibrillation |
|
| MedDRA Classification |
| 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 characterize the relationship between anti IIa activity, a biomarker used to detect
changes in coagulability, and SB424323 dosage. |
|
| E.2.2 | Secondary objectives of the trial |
To compare the safety and tolerability of BID dosing with SB424323 250 mg, 375 mg
500 mg and placebo (all in addition to aspirin 325 mg daily) in subjects with NVAF with a low or intermediate risk for stroke. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria
apply:
1. Male or female ≥18 years of age at the time informed consent is signed.
2. Women must be surgically sterile or postmenopausal (greater than 1 year since their
last menstrual period with an FSH level of greater than 30 IMU/ml). Surgically sterile is defined as a total hysterectomy or bilateral oopherectomy. A tubal ligation
is not acceptable as surgically sterile.
3. Diagnosis of chronic non valvular atrial fibrillation with a low or intermediate risk
for stroke within 6 months of the screening visit confirmed by either ECG or
telemetry.
• Subjects diagnosed with paroxysmal AF, persistent AF or permanent AF are
all eligible for participation in the study. Subjects with atrial flutter do not
qualify for the study.
• Subjects previously diagnosed with hyperthyroidism, with normal thyroid
function and continued AF are eligible for participation in the study.
A subject will be considered at a low or intermediate risk for stroke if one of the
following applies:
• Subjects ≤60 years of age with no heart disease
• Subjects <60 years of age with heart disease but no risk factors (defined as:
heart failure, left ventricular ejection fraction less than 35%, diabetes, history of
hypertension and prior embolic event)
• Subjects ≥60 yrs and ≤75 years of age with no risk factors and no heart disease
4. Is available for participation in the study for at least 20 weeks. |
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria
apply:
1. Previous myocardial infarction, stroke (ischemic or hemorrhagic), TIA or other
cardiovascular event
2. Subjects with mechanical prosthetic valve or rheumatic valvular disease
3. History of hypertension (defined as medical treatment for the disease within the past
year), diabetes (defined as medical treatment for the disease within the past year) or
prior embolic event
4. Subjects with a LVEF less than 35%
5. Subjects that are greater than 75 years of age at the screening visit or subjects that
will become greater than 75 years of age during their participation in the study.
6. Subjects with hepatic disease as defined by any ALT, AST or bilirubin abnormality
at the screening visit.
7. Subjects with chronic liver disease (e.g. Hepatitis C)
8. Renal insufficiency as defined by creatinine clearance less than 30 ml/min
9. Subjects requiring treatment with Class III anti-arrhythmic drugs
10. Subjects with an ongoing requirement for any anti-thrombotic drug therapy such as a
vitamin K antagonist, heparin (standard unfractionated or low molecular weight), heparinoid, direct thrombin inhibitor, GPIIb/IIIA receptor antagonist, thrombolytic
agent or intravenous dextran.
11. Subject requires ongoing treatment with clopidogrel.
12. Subject requires ongoing treatment with amiodarone or dofetilide.
13. Subject requires ongoing treatment with a calcium channel blocker.
14. History of aspirin sensitivity or any contraindication to aspirin
15. History of gastrointestinal bleed or gastrointestinal intolerance when taking aspirin
16. Subjects with a history of hypercoagulable syndrome or vasculitis
17. Subjects with conditions that subject them to an increased risk of bleeding such as:
• Previous gastrointestinal bleeding
• Hemorrhagic disorders
• History of intraocular, spinal, intracranial, retroperitoneal bleeding
• Major surgical procedure or major hemorrhagic event within 30 days prior to
screening visit
18. Subjects with anemia as defined by hemoglobin <12 g/dL.
19. NVAF secondary to other reversible disorders such as thyrotoxicosis.
20. Malignancy within the past five years [other than superficial squamous cell
carcinoma which is non-invasive on pathology, basal cell carcinoma which is
successfully treated with local excision, and/or cervical cancer in situ treated
definitively at least 6 months prior to screening].
21. Life expectancy less than 1 year
22. Has any concurrent medical condition or any clinically significant abnormality
identified on the screening physical examination, laboratory tests or
electrocardiogram, which otherwise contraindicates participation in a clinical trial
with a new chemical entity.
23. Has a history of alcohol abuse, substance abuse or both, within the past year, as
determined by the investigator.
24. Use of any investigational drug or device within 30 days or 5 half lives (whichever is
longer) prior to screening.
25. There is a known hypersensitivity to any drugs chemically related to the
investigational product.
26. In the opinion of the Investigator, has a risk of non-compliance with study
procedures, cannot read, and cannot understand study-related materials.
27. Subjects with known gastric bypass, malabsorption syndrome or short gut syndrome.
28. Subjects that are self identified as being Japanese heritage. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint will be anti IIa activity over the course of the study. |
|
| 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 | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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