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Trial record 1 of 4 for:    hestia 4
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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 : June 10, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE March 16, 2018
First Posted Date  ICMJE April 10, 2018
Last Update Posted Date June 10, 2019
Actual Study Start Date  ICMJE March 28, 2018
Actual Primary Completion Date May 7, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
  • Peak Plasma Concentration (Cmax) of Ticagrelor [ Time Frame: 1,2,4,6 hours post dose ]
    This measure is obtained from observed plasma concentrations
  • Area under plasma concentration curve [ Time Frame: 1,2,4,6 hours post dose ]
    This measure is obtained from the population PK analysis
  • CL/F (Oral clearance) [ Time Frame: 1,2,4,6 hours post dose ]
    This measure is obtained from the population PK analysis.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
  • Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX) [ Time Frame: 1,2,4,6 hours post dose ]
  • 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 ]
    Questionnaire with one five-options question reflecting different degrees of patients willingness to swallow, from "swallowed without problem" to "vomited up medication".
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PK Study of Ticagrelor in Children Aged Less Than 24 Months, With Sickle Cell Disease (HESTIA4)
Official Title  ICMJE 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)
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
Study has an Open-Label design.
Primary Purpose: Other
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Treatment arm
Single dose of ticagrelor based on age
Intervention: Drug: Ticagrelor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 7, 2019)
21
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2018)
23
Actual Study Completion Date  ICMJE May 7, 2019
Actual Primary Completion Date May 7, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 23 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Italy,   Kenya,   Lebanon,   Spain,   United Kingdom
Removed Location Countries Egypt,   Ghana
 
Administrative Information
NCT Number  ICMJE NCT03492931
Other Study ID Numbers  ICMJE D5136C00010
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP