PK Study of Ticagrelor in Children Aged less than 24 Months, with Sickle Cell Disease (HESTIA4) - HESTIA4

Exclusion Criteria

• 1. History of transient ischaemic attack or cerebrovascular event/accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy.
• 2. Significantly underdeveloped with regards to height, weight or head circumference for age, as judged by the Investigator.
• 3. Severe developmental delay (eg, cerebral palsy or mental retardation).
• 4. Receiving chronic treatment (>3 days/week) with non-steroidal anti-inflammatory drugs (NSAIDs).
• 5. Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
• 6. Moderate or severe hepatic impairment, defined as laboratory values of alanine aminotransferase (ALT) >2 × upper limit of normal (ULN), total bilirubin >2 × ULN (unless judged by the Investigator to be caused by haemolysis), albumin <35 g/L and international normalised ratio (INR) >1.4, or symptoms of liver disease (eg, ascites).
• 7. Renal failure requiring dialysis.
• 8. Active pathological bleeding or increased risk of bleeding complications according to the Investigator.
• 9. Haemoglobin <6 g/dL from test performed at Screening (Visit 1).
• 10. Platelets <100 × 10^9/L from test performed at Screening (Visit 1).
• 11. Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second or third degree atrioventricular block).
• 12. Concomitant oral or intravenous therapy with moderate or strong CYP3A4 inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers that have not been stopped at least 5 half-lives before dose administration.
• 13. Patient breastfed by mother who is under treatment of strong CYP3A4 inhibitors,
• 14. Active untreated malaria. Patients with suspected malaria at Screening (Visit 1) will be tested.
• 15. Surgical procedure planned to occur during the study including 5 days after ticagrelor administration.
• 16. Known hypersensitivity or contraindication to ticagrelor.
• 17. Concern for the inability of the patient or parents to comply with study procedures and/or follow-up.
• 18. Any condition which, in the opinion of the Investigator, would make it unsafe or unsuitable for the patient to participate in this study.
• 19. Previously administered ticagrelor in the present study.
• 20. Participation in another clinical study with an investigational medicinal product (IMP) or device during the last 30 days preceding screening/enrolment.
• 21. Involvement of member of patient’s family in planning and/or conduct of the study (applies to both AstraZeneca personnel and personnel at study centre).