Stable Coronary Artery Disease AZD6140 is under development for the prevention of thrombotic events in patients with non-ST and ST elevation coronary syndromes MedDRA version: 9.1 Level: HLT Classification code 10011085 Term: Ischaemic coronary artery disorders
Conditions
Interventions
Product Name: Ticagrelor
Product Code: AZD6140
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ticagrelor
CAS Number: 274693-27-5
Current Sponsor code: AZD6140
Concentration unit: mg mill
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1, Provision of written informed consent 2, Documented stable CAD fulfilling any of the following, and taking ASA daily treament for at least 1 month prior to receiving their first dose of study medication: stable angina pectoris with objective evidence of CAD, previous myocardial infarction history, previous revascularisation history 3, Aged 18 years or older, male or female 4, Females of childbearing potential must: have a negative urine or blood pregancy test at enrolment, currently be using a hormonal contraceptive and agree to continue its use in addition to using barrier local contraception from screening through stuy completion. Women not using hormonal contraception must use double barrier local contraception Genetic substudy Provide written informed consent Radioligand substudy Provide written informed consent 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. Patients who had ACS within 12 months of screening 2. Any of the following requiring antithrombotic treatment (eg, warfarin, clopidogrel, ASA dose other than 75 mg to 100 mg daily) during the study period: atrial fibrillation, mitral stenosis or prosthetic heart valve, coronary stent 3. Concomitant therapy with moderate or strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic index, or strong CYP3A inducers within 14 days of study treatment. For example: Moderate inhibitors: Amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, verapamil Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir. Substrates with narrow therapeutic index: cyclosporine, quinidine. Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine. The sponsor should be consulted for enrollment with any concomitant medicines which are suspected of undergoing moderate/strong drug-drug interaction 4. Increased bleeding risk including: Gastrointestinal (GI) bleeding within 30 days of dosing Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding Major trauma within 30 days of dosing Sustained uncontrolled hypertension (systolic blood pressure [SBP] >180 mmHg or diastolic blood pressure [DBP] >100 mmHg) History of hemorrhagic disorders that can increase the risk of bleeding, eg, haemophilia, von Willebrand’s disease Inability to discontinue required concomitant therapy with non-selective non-steroidal anti-inflammatory drug (NSAID) at screening Patients that have recently used within 30 days of dosing any oral or parenteral antithrombotic agents, with the exception of clopidogrel and ASA. Platelet count less than 100,000 mm3 or hemoglobin (Hb) <10 g/dL 5. Diabetic patients with glycated Hb (HbA1c)=10% 6. Contraindication or other reason that clopidogrel, ASA, or AZD6140 should not be administered (eg, hypersensitivity, active bleeding, major surgery within 30 days of dosing, any bleeding tendency [coagulation defects], acute or chronic liver disease etc.) 7. History of drug addiction or alcohol abuse in the previous 2 years 8. Patient requires dialysis or has a creatinine clearance (CLCR) <30 mL/min as calculated by the Cockcroft-Gault equation. 9. Participation in another investigational drug or device study within 30 days of dosing 10. Current smokers using more than 1 pack per day (or equivalent) of any tobacco containing products in the past 1 month 11. Recent (within 30 days of dosing) blood donation 12. Women who are pregnant or lactating 13. Patients that are scheduled for revascularization (eg, PCI, CABG) during the study period 14. Any acute or chronic unstable condition in the past 30 days or other condition which, in the opinion of the investigator, may either put the patient at risk or influence the result of the study (eg, active cancer, risk for non-compliance, risk for being lost to follow-up) 15. Patients with raised serum potassium (=5.5 mmol/L) 16. Involvement in the planning and conduct of the study (applies to AstraZeneca or delegate staff, and study site staff) 17. Previous enrolment or randomisation of treatment in the present study 18. A suspected/manifested infection according to the World Health Organization (WHO) risk categories 2, 3 and 4 19. Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or human immunodeficiency virus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the effect of AZD6140 on inhibition of platelet aggregation compared with clopidogrel in patients previously identified as non-responsive to clopidogrel;Secondary Objective: ¤ compare inhibition of platelet aggregation (IPA), platelet aggregation and biomarker expression in clopidogrel responsive patients when directly switched from clopidogrel to AZD6140, as opposed to continuing treatment with clopdogrel without interruption ¤ compare IPA, platelet aggregation and biomarker expression in clopidogrel responsive patients when directly switched from AZD6140 to clopidogrel, as opposed to continuing treatment with AZD6140 without interruption ¤ assess the general tolerability of a direct swith from clopidogrel to AD6140 without a washout;Primary end point(s): Pharmacodynamic Primary outcome variables: - Proportion of clopidogrel non-responders who respond to antiplatelet therapy as measured by 20 µM IPA (final extent) at 4 hours post dose at steady state. The primary definition of response to treatment in this trial is IPA > 10%. Pharmacokinetic Exploratory analyses of PK/PD relationships between AZD6140 plasma concentrations and pharmacodynamic parameters may be conducted. Safety Safety will be assessed via the following variables: adverse events (including bleeding events), safety labs (clinical chemistry, haematology and urinalysis), 12-lead electrocardiograms, physical examination and vital signs (blood pressure, pulse and respiratory rate). Genetics The genetic research component will provide data for retrospective analysis. Any result will not form part of the main study database or the Clinical Study Report. Radioligand Pilot data for studying whether AZD6140 affects the binding of clopidogrel active metabolite to the P2Y 12 receptor. | — |
Countries
Denmark, United Kingdom
Outcome results
None listed