Non-ST Segment Elevation Acute Coronary Syndromes MedDRA version: 7.0 Level: LLT Classification code 10051592
Conditions
Interventions
Product Code: AZD6140
Pharmaceutical Form: Film-coated tablet
CAS Number: 274693-27-5
Current Sponsor code: AZD6140
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Non-ST segment elevation ACS (index event) within the previous 48 hours documented by ischaemic symptoms of >10 minutes’ duration at rest, plus at least one of the following criteria described in either a or b: a. Biochemical marker evidence of MI: - Troponin T or I > local MI decision limit on at least one occasion during the first 24 hours after admission for the index clinical event. - CK-MB, preferably CK-MB mass, >local MI decision limit on at least one occasion during the first 24 hours after admission for the index clinical event. - In the absence of troponin or CK-MB, total CK >2x local MI decision limit during the first 24 hours after admission for the index clinical event. b. ECG changes indicative of ischaemia: - ST segment depression >0.5 mm (0.05 mV) in 2 or more contiguous leads. - Transient ST segment elevation 1 mm (0.1 mV) in 2 or more contiguous leads. - T-wave abnormalities - inversion >1 mm (0.1 mV) in 2 or more contiguous leads. 2. Provision of written informed consent. 3. Females and males aged 18 years and over. 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
Exclusion criteria: 1. Persistent ST segment elevation >20 minutes. 2. More than 48 hours from onset of symptoms of non-ST segment elevation ACS to expected initiation of therapy (first dose). 3. PCI within the 48 hours prior to the index event or PCI within the 48 hours prior to randomisation. 4. Coronary angiography in the 48 hours prior to randomisation showing no significant narrowing of the coronary arteries or 180 mmHg or diastolic >100 mmHg with or without anti-hypertensive treatment (as demonstrated by repeated BP measurements >180/100 mmHg including the final BP measurement before randomisation). e. Haemorrhagic disorder. f. Major surgical procedure or trauma within the 30 days prior to randomisation. g. Intracranial aneurysm or vascular malformation. 6. Chronic oral anticoagulation required eg, atrial fibrillation, mitral stenosis, rheumatic valve disease, prosthetic heart valves; or concomitant oral anticoagulation therapy within the 7 days prior to randomisation. 7. Chronic daily dosing with non-selective NSAIDs required eg, rheumatoid arthritis. 8. Thrombolytic therapy administered for STEMI or any other condition in the 7 days prior to randomisation. 9. Contraindications for ASA treatment, including allergy or intolerance that would prevent its use during the study. 10. Concomitant therapy with digoxin or strong cytochrome P450 3A4 inhibitors or cytochrome P450 3A4 substrates with a narrow therapeutic index. 11. Known lactose intolerance. 12. Serum creatinine level >3.0 mg/dL (265 mmol/L). 13. Known active liver disease or Visit 1 elevated liver function tests of ALT >2x ULN or total bilirubin >1.5x ULN (local laboratory reference ranges). 14. Haemoglobin (Hb) level <100 g/L (6.2 mmol/L). 15. Platelet count <100x109/L. 16. CABG within the 3 months prior to randomisation. 17. Non-haemorrhagic stroke within the 30 days prior to randomisation. 18. Active cancer (excluding skin basal cell carcinoma). 19. Female of childbearing potential (female patients must be either post-menopausal for 1 year, or surgically sterile). 20. Patients with disease or disorders which in the opinion of the investigator, may either put the patient at risk because of participation in the study or inappropriately influence the result of the study, or the patient’s ability to participate in the study. 21. Inability to complete the study according to the protocol, eg, inability to complete questionnaires in local language. 22. Participation in another investigational drug study within one month prior to randomisation or previous randomisation in this study. 23. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational site). 24. Previous enrolment or randomisation of treatment in the present study. - Additional exclusion criteria for patients participating in the PK/PD sub-study: 25. Concomitant treatment with GpIIb/IIIa receptor antagonists within 24 hours (tirofiban, integrilin) or 7 days (abciximab) prior to randomisation. 26. Concomitant tre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the safety and tolerability of different doses of AZD6140 in the presence of acetyl salicylic acid (ASA), compared with clopidogrel plus ASA in patients with non-ST segment elevation ACS by evaluation of total bleeding events (excluding minimal bleeds) observed within the first 4 weeks of treatment (Day 29). ;Secondary Objective: ·To assess the pharmacodynamic effects of AZD6140 in the presence of ASA compared to clopidogrel plus ASA (in clopidogrel-naïve patients). ·To compare the platelet aggregation response to AZD6140 on Day 1 in clopidogrel-naïve patients and clopidogrel pre-treated patients. ·To evaluate the pharmacokinetics of AZD6140 and its active metabolite AR-C124910XX. ·To evaluate the relationship between AZD6140 pharmacokinetics and platelet aggregation inhibition. ·To evaluate the relationship between AZD6140 and AR-C124910XX exposures and the occurrence of major and minor bleeding. ·To compare the safety and tolerability of AZD6140/ASA with clopidogrel/ASA. ·To assess the safety and tolerability of the AZD6140 loading dose. ·To evaluate the effect of AZD6140 on the inflammatory markers and comparing the changes to those achieved with clopidogrel. ·;Primary end point(s): Total bleeding events (excluding minimal bleeds) observed within the first four weeks of treatment Total bleeding events (excluding minimal) at Days 57 and 85, plus overall bleeding rate using total patient exposure Each individual bleeding category (excluding minimal), separately Discontinuations due to bleeding adverse events Bleeding (excluding minimal) associated with coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) vs bleeding (excluding minimal) not associated with CABG or PCI Number of transfusions, categorised as 1 unit, 2-3 units or equal to or more than 4 units. | — |
Countries
Czech Republic, Denmark, Finland, Spain
Outcome results
None listed