Arterial thrombosis MedDRA version: 9.1 Level: LLT Classification code 10003178 Term: Arterial thrombosis
Conditions
Interventions
Product Code: AZD6140
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ticagrelor
CAS Number: 274693-27-5
Current Sponsor co
Sponsors
AstraZeneca AB, European Regulatory Affairs
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study patients must fulfil all of the following criteria: 1. Provision of written informed consent (by patient or appropriate designee according to local regulations) 2. Documented stable CAD fulfilling any of the following, and taking 75-100mg ASA daily treatment: - Stable angina pectoris with objective evidence of CAD - Previous MI history - Previous revascularization history, (i.e., PCI or coronary artery bypass graft [CABG]) 3. Aged 18 years or older, male or female 4. Females of childbearing potential (i.e., females who are not post-menopausal or surgically sterile) must: - have a negative urine or blood pregnancy test at enrolment and prior to randomisation at Visit 2 - currently be using a hormonal contraceptive and agree to continue its use in addition to using double-barrier local contraception (i.e., intra-uterine device plus spermicidal and condom for male partner) from screening through study completion. For inclusion in the genetic research, patients must sign the informed consent for genetic research. 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: Any of the following is regarded as a criterion for exclusion from the study: 1. Any indication (e.g., atrial fibrillation, mitral stenosis or prosthetic heart valve, coronary stent) for antithrombotic treatment (e.g., warfarin, clopidogrel, ASA dose other than 75 to 100 mg daily) during study period 2. 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 3. Increased bleeding risk including: - Recent (within 30 days) GI bleeding - Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding - Recent (within 30 days of dosing) major trauma - Sustained uncontrolled hypertension (systolic blood pressure [SBP]>180mmHg or diastolic blood pressure [DBP]>100mmHg) - History of hemorrhagic disorders that can increase the risk of bleeding, e.g., 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 screening) any oral or parenteral antithrombotic agents (Section 3.7), with the exception of clopidogrel and ASA - Platelet count less than 100,000 mm3 or hemoglobin <10 g/dL 4. History of congestive heart failure, chronic obstructive pulmonary disease, chronic or active asthma, “interstitial lung disease”, other known pulmonary disease that will influence the cardiopulmonary function test interpretation 5. Diabetic patients with HbA1c=10% 6. Contraindication or other reason that clopidogrel, ASA, or AZD6140 should not be administered (e.g., 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 <30mL/min as calculated by the Cockcroft-Gault equation: (140-age) x WT Creatinine clearance = --------------------------------- (x 0.85 for females) 72 x serum creatinine where WT is weight in kg, serum creatinine is in mg/dL 9. Participation in another investigational drug or device study within 30 days of dosing 10. Recent (within 30 days of dosing) blood donation 11. Women who are pregnant or lactating 12. Patients that are scheduled for revascularization (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The co-primary endpoints are IPA (inhibition of platelet aggregation) at 2 hours after the first dose (final and maximum extent) and the slope of the IPA curves (final and maximum extent) from 4 hours to 72 hours after the last dose.; Main Objective: The primary objective of this study is to determine the onset and offset of antiplatelet effect of AZD6140 compared to clopidogrel by evaluation of: • The percent inhibition of platelet aggregation (IPA) by light transmittance aggregometry (LTA) at 2 hours after 1st dose of study drug • The difference in slope of IPA effect curve by LTA after last dose of study drug ; Secondary Objective: The secondary objectives of this study are to: • Investigate if AZD6140 has any clinically significant cardiopulmonary effect compared to clopidogrel and placebo by assessment of cardiopulmonary function • Assess safety and tolerability of AZD6140 compared with clopidogrel and placebo by evaluation of adverse events, laboratory testing, 12-lead electrocardiogram, vital signs and physical examinations • To evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of AZD6140 and its active metabolite AR –C124910XX by assessment of PK and PD parameters • Determine the effect on platelet aggregation of AZD6140 compared to clopidogrel with respect to onset and offset by measuring 5 and 20 µM ADP induced platelet aggregation | — |
Countries
United Kingdom
Outcome results
None listed