A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease

Multicenter, Open-label, Randomised, Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor Followed by a Double-blind, Randomised, Parallel-group, Placebo-controlled 4 Weeks Extension Phase in Paediatric Patients With Sickle Cell Disease

The purpose of this Phase II dose-ranging study is to investigate pharmacokinetic (PK) and pharmacodynamic (PD) properties of various doses of ticagrelor followed by 4 weeks of twice-daily treatment in paediatric patients with sickle cell disease

This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double blind, placebo-controlled extension phase in paediatric patients with sickle cell disease (SCD).

Part A: Patients will be randomised 1:1 to receive one of two dosing schedules consisting of two single weight-adjusted doses of ticagrelor. Pharmacokinetic (PK) parameters and pharmacodynamic (PD) measurements will be determined following each dose. Platelet aggregation will be measured using the VerifyNow™ P2Y12 assay.

Following these 2 single doses, all patients will receive open-label one-week treatment with ticagrelor twice daily to determine tolerability prior to randomisation into Part B.

Part B: In this part patients will be randomised (2:1 ratio) to ticagrelor twice daily or placebo for a 4-week treatment phase.

During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC) and for other disease manifestations such as daily pain, analgesic use and complications of SCD.

Inclusion criteria

• Children aged ≥2 to <18 years of age
• Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/β0)

Exclusion criteria

• At risk for haemorrhagic or bradycardic events
• Significant hepatic impairment
• Renal failure requiring dialysis
• Concomitant oral or intravenous therapy with strong CYP3A4 (cytochrome) inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers.
• Surgical procedure planned to occur during the study.
• Patients who are currently pregnant or breastfeeding or planning to become pregnant during the study.
• Patients who have known hypersensitivity or contraindication to ticagrelor.