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

NCT03492931 | Completed Phase 1 FDA Drug

• 1 other identifier: D5136C00010
• Study Type: interventional
• Target: 21
• Locations: 6 countries
• Sites: 8

Brief Summary

The purpose of this Phase I study is to investigate the pharmacokinetic properties of ticagrelor in pediatric patients from 0 to less than 24 months with sickle cell disease. Ticagrelor dose level adjustment will require a Protocol amendment and regulatory approval.

Conditions

Sickle Cell Disease

Keywords

Hb SS disease, Hb S Beta 0 Thalassemia

Outcome Measures

Primary Outcomes (3)

• Peak Plasma Concentration (Cmax) of Ticagrelor

  This measure is obtained from observed plasma concentrations

  1,2,4,6 hours post dose

• Area under plasma concentration curve

  This measure is obtained from the population PK analysis

  1,2,4,6 hours post dose

• CL/F (Oral clearance)

  This measure is obtained from the population PK analysis.

  1,2,4,6 hours post dose

Secondary Outcomes (3)

• Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX)

  1,2,4,6 hours post dose

• Area under plasma concentration curve

  1,2,4,6 hours post dose

• Assessment of ticagrelor suspension for palatability

  Day 1, single timepoint assessment

Study Arms (1)

Treatment arm

EXPERIMENTAL

Single dose of ticagrelor based on age

Drug: Ticagrelor

Interventions

Ticagrelor DRUG

Patients will receive a single dose of ticagrelor

Also known as: AR-C124910XX is an active metabolite of ticagrelor given orally in a single dose. It will be measured, but it won't be given directly to subjects.

Treatment arm

Eligibility Criteria

• Age: 1 Day - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Paediatric patients aged \<24 months, diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassemia (HbS/β0), as confirmed by high performance liquid chromatography or haemoglobin electrophoresis.
• Body weight ≥5 kg at the time of screening.
• If treated with an anti-sickling agent such as hydroxyurea, the weight-adjusted dose must be stable for 3 months before screening/enrolment.
• Provision of signed and dated written informed consent from parents/legal guardians prior to any study specific procedures not part of standard medical care.

You may not qualify if:

• 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.
• Significantly underdeveloped with regards to height, weight or head circumference for age, as judged by the Investigator.
• Severe developmental delay (eg, cerebral palsy or mental retardation).
• Receiving chronic treatment (\>3 days/week) with non-steroidal anti-inflammatory drugs (NSAIDs).
• Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
• 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).
• Renal failure requiring dialysis.
• Active pathological bleeding or increased risk of bleeding complications according to the Investigator.
• Haemoglobin \<6 g/dL from test performed at Screening (Visit 1).
• Platelets \<100 × 10\^9/L from test performed at Screening (Visit 1).
• Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second or third degree atrioventricular block).
• 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.
• Patient breastfed by mother who is under treatment of strong CYP3A4 inhibitors,
• Active untreated malaria. Patients with suspected malaria at Screening (Visit 1) will be tested.
• Surgical procedure planned to occur during the study including 5 days after ticagrelor administration.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (8)

Research Site

Edegem, 2650, Belgium

Location

Research Site

Genova, 16100, Italy

Location

Research Site

Kisumu, 40100, Kenya

Location

Research Site

Nairobi, 00100, Kenya

Location

Research Site

Beirut, 11-0236, Lebanon

Location

Research Site

Tripoli, 1434, Lebanon

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• Duniva Inusa BP, Inati A, Maes P, Githanga J, Ogutu B, Abboud MR, Miano M, Cela E, Nduba V, Niazi M, Astrand M, Persson K, Berggren A, Carlson G. Pharmacokinetics and safety of ticagrelor in infants and toddlers with sickle cell disease aged <24 months. Pediatr Blood Cancer. 2021 May;68(5):e28977. doi: 10.1002/pbc.28977. Epub 2021 Feb 25.

  PMID: 33629819 DERIVED

Related Links

• Study results information posted to AstraZeneca Cinical Trials Webiste

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Study has an Open-Label design.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2018
• First Posted: April 10, 2018
• Study Start: March 28, 2018
• Primary Completion: May 7, 2019
• Study Completion: May 7, 2019
• Last Updated: May 10, 2021

Record last verified: 2021-05

Locations

IT (1); GB (1); BE (1); ES (1); LE (2); KE (2)