A clinical study of the level of drug (Ticagrelor) in blood in infants and toddlers, aged 0 to less than 24 months with Sickle Cell Disease

Phase 1

Conditions: Sickle Cell Disease
MedDRA version: 20.0 Level: LLT Classification code 10040644 Term: Sickle cell disease System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2017-003641-14-BE

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 21

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 × 10E9/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, as defined in Appendix E of the protocol.
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).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the PK properties of ticagrelor after a single oral dose;<br> Secondary Objective: - To determine the PK properties of the active metabolite (AR-C124910XX) after a single oral dose<br> - To assess the acceptability and the palatability of a single oral dose of ticagrelor<br> - To assess safety and tolerability of a single oral dose of ticagrelor<br> ;Primary end point(s): Observed ticagrelor plasma concentrations as well as PK parameters obtained using a population PK analysis approach, eg, CL/F (oral clearance), Cmax, and AUC;Timepoint(s) of evaluation of this end point: 1, 2, 4 and 6 hours postdose

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): a- Observed plasma concentrations of the active metabolite (AR-C124910XX) as well as PK parameters obtained using a population PK analysis approach, eg, Cmax, and AUC<br> b- Observer assessment of acceptability and palatability<br> ;<br> Timepoint(s) of evaluation of this end point: a - 1, 2, 4 and 6 hours postdose<br> b - during administration of dose<br>

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