Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03492931
Recruitment Status : Completed
First Posted : April 10, 2018
Last Update Posted : May 10, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Ticagrelor Phase 1

Detailed Description:

Study design This Phase I paediatric study (in patients aged 0 to <24 months) with ticagrelor is planned to be a multi-centre, open-label, single dose study.

Primary Objective:

To determine the PK properties of ticagrelor after a single oral dose

Secondary Objectives:

To determine the PK properties of the active metabolite (AR-C124910XX) after a single oral dose To assess the acceptability and the palatability of a single oral dose of ticagrelor

Safety Objective:

To assess safety and tolerability of a single oral dose of ticagrelor

Duration of treatment At least 20 eligible patients will receive a single open label oral dose of ticagrelor on Day 1.

Statistical methods A population PK analysis approach will be used to determine the PK parameters of ticagrelor and its metabolite AR-C124910XX in paediatric patients aged 0 to <24 months eg, CL/F (oral clearance) (only for ticagrelor) and AUC.

The PK will also be described by presenting the observed plasma concentrations of Ticagrelor and its active metabolite for all individuals, as well as corresponding descriptive statistics.

No statistical comparisons are planned for the primary or secondary objectives, which will be summarised descriptively

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Study has an Open-Label design.
Primary Purpose: Other
Official 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)
Actual Study Start Date : March 28, 2018
Actual Primary Completion Date : May 7, 2019
Actual Study Completion Date : May 7, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ticagrelor

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Treatment arm
Single dose of ticagrelor based on age
 Drug: Ticagrelor
Patients will receive a single dose of ticagrelor
Other Name: 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Peak Plasma Concentration (Cmax) of Ticagrelor [ Time Frame: 1,2,4,6 hours post dose ]
    This measure is obtained from observed plasma concentrations

  2. Area under plasma concentration curve [ Time Frame: 1,2,4,6 hours post dose ]
    This measure is obtained from the population PK analysis

  3. CL/F (Oral clearance) [ Time Frame: 1,2,4,6 hours post dose ]
    This measure is obtained from the population PK analysis.


Secondary Outcome Measures :
  1. Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX) [ Time Frame: 1,2,4,6 hours post dose ]
  2. Area under plasma concentration curve [ Time Frame: 1,2,4,6 hours post dose ]
  3. Assessment of ticagrelor suspension for palatability [ Time Frame: Day 1, single timepoint assessment ]
    Questionnaire with one five-options question reflecting different degrees of patients willingness to swallow, from "swallowed without problem" to "vomited up medication".


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Day to 23 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  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).
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03492931


Locations
Layout table for location information
Belgium
Research Site
Edegem, Belgium, 2650
Italy
Research Site
Genova, Italy, 16100
Kenya
Research Site
Kisumu, Kenya, 40100
Research Site
Nairobi, Kenya, 00100
Lebanon
Research Site
Beirut, Lebanon, 11-0236
Research Site
Tripoli, Lebanon, 1434
Spain
Research Site
Madrid, Spain, 28007
United Kingdom
Research Site
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
AstraZeneca
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03492931    
Other Study ID Numbers: D5136C00010
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: May 10, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AstraZeneca:
Hb SS disease, Hb S Beta 0 Thalassemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Ticagrelor
 Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs