Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AZD3366 in Healthy Subjects, Japanese and Chinese Subjects

Exclusion Criteria

• 1. Subjects having history of the following are excluded:
• • Any clinically important disease or disorder which, may put the subject at risk, or influence the results or the subject’s ability to participate in the study.
• • History or presence of gastrointestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
• • Hemophilia, von Willebrand´s disease, lupus anticoagulant or other diseases/syndromes that can either alter or increase the propensity of bleeding.
• • Any clinically significant non-traumatic bleed or clinically significant enhanced bleeding.
• • Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD3366 or to ASA or ticagrelor.
• 2. Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, coagulation parameters, including but not limited to the list below:
• • Alanine aminotransferase > upper limit of normal (ULN)
• • Aspartate aminotransferase > ULN
• • Creatinine > ULN
• • White blood cell count < lower limit of normal (LLN)
• • Hemoglobin < LLN
• • Platelet count < 150,000/µL
• • Total bilirubin 1.2 x > ULN
• 3. Subjects with positive serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus.
• 4. Any abnormal vital signs, after 10 minutes supine rest, as defined in the list below, at the Screening Visit and/or Day -1:
• − Systolic blood pressure (BP) < 90 mmHg or > 140 mmHg.
• − Diastolic BP < 50 mmHg or > 90 mmHg.
• − Heart rate <45 or >85 beats per minute.
• 5. Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG, which may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology.
• 6. Current smokers or those who have smoked or used nicotine products within the previous 3 months, or history of alcohol abuse or excessive intake of alcohol.
• 7. Use of drugs with enzyme inducing properties such as St John’s Wort within 3 weeks prior to the first administration of IMP.
• 8. Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega-dose vitamins and minerals during the 2 weeks prior to the first administration of IMP or 5 x the half-life of the drug (whichever is longer).
• 9. Plasma donation within one month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
• 10. COVID-19 vaccination has been administered and a period of less than 14 days has elapsed after the second dose of the vaccine prior to randomization.
• 11. Received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days (or 5 half-lives, whichever is longer) of the first administration of IMP in this study.
• 12. Scheduled surgery, including dental surgery, within 8 weeks of the scheduled completion date of the study.
• 13. Anti-platelet therapy, anticoagulation therapy (i.e., warfarin, factor Xa inhibitors, direct thrombin inhibitors, or heparin), or thrombolytic use, in the past month prior to randomization or planned use during the duration of the study.
• 14. Use of non-steroidal anti-inflammatory drugs (including ibuprofen) within 3 days prior to the randomization.
• 15. Use of potent cytochrome 3A4/3A5 and/or P-glycoprotein inhibiting or inducing drugs during the 2 weeks prior to the first administration of IMP or 5 x the half-life of the drug (whichever is longer).
• 16. Subjects who are vegans.
• 17. Subjects who cannot communicate reliably with the investigator.
• 18. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.