PK Study of Ticagrelor in Children Aged Less Than 24 Months, With Sickle Cell Disease (HESTIA4)

• Register: ClinicalTrials.gov
• Last refreshed on: 17 May 2021
• Main ID: NCT03492931
• Date of registration: 16/03/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: PK Study of Ticagrelor in Children Aged Less Than 24 Months, With Sickle Cell Disease (HESTIA4) HESTIA4
• Scientific title: A Multi-centre, Phase I, Open-label, Single-dose Study to Investigate Pharmacokinetics (PK) of Ticagrelor in Infants and Toddlers, Aged 0 to Less Than 24 Months, With Sickle Cell Disease (HESTIA4)
• Date of first enrolment: March 28, 2018
• Target sample size: 21
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03492931
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Belgium, Egypt, Ghana, Italy, Kenya, Lebanon, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Paediatric patients aged <24 months, diagnosed with homozygous sickle cell (HbSS) or
sickle beta-zero-thalassemia (HbS/ß0), as confirmed by high performance liquid
chromatography or haemoglobin electrophoresis.

2. Body weight =5 kg at the time of screening.

3. If treated with an anti-sickling agent such as hydroxyurea, the weight-adjusted dose
must be stable for 3 months before screening/enrolment.

4. Provision of signed and dated written informed consent from parents/legal guardians
prior to any study specific procedures not part of standard medical care.

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).



Age minimum: N/A
Age maximum: 23 Months
Gender: All

Health Condition(s) or Problem(s) studied

Sickle Cell Disease

Intervention(s)

Drug: Ticagrelor

Primary Outcome(s)

CL/F (Oral clearance) [Time Frame: 1,2,4,6 hours post dose]

Area under plasma concentration curve [Time Frame: 1,2,4,6 hours post dose]

Peak Plasma Concentration (Cmax) of Ticagrelor [Time Frame: 1,2,4,6 hours post dose]

Secondary Outcome(s)

Area under plasma concentration curve [Time Frame: 1,2,4,6 hours post dose]

Assessment of ticagrelor suspension for palatability [Time Frame: Day 1, single timepoint assessment]

Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX) [Time Frame: 1,2,4,6 hours post dose]

Secondary ID(s)

D5136C00010

Source(s) of Monetary Support

Please refer to primary and secondary sponsors