A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease (HESTIA 1)

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease

Treatments: Drug: Ticagrelor Dose 1b + Dose 2b; Drug: Ticagrelor Dose 1a + Dose 2a

Study type: Interventional

Funder types: Industry

Identifiers

NCT02214121

D5136C00007

2014-001006-18 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 46 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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46 participants in 2 patient groups

Ticagrelor Dose 1a + Dose 2a

Other group

Description:

Part A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing.

Treatment:

Drug: Ticagrelor Dose 1a + Dose 2a

Ticagrelor Dose 1b + Dose 2b

Other group

Description:

Part A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing.

Treatment:

Drug: Ticagrelor Dose 1b + Dose 2b