Investigation of platelet aggregation in paediatric patients with sickle cell disease MedDRA version: 18.1 Level: LLT Classification code 10040644 Term: Sickle cell disease System Organ Class: 100000004850
Conditions
Interventions
Product Name: ticagrelor
Product Code: AZD6140
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: ticagrelor
CAS Num
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Children aged =2 to 16 kg diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/ß0) 2.If treated with an anti-sickling agent such as hydroxyurea, the weight adjusted dose must be stable for 1 month before enrolment Are the trial subjects under 18? yes Number of subjects for this age range: 50 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
Exclusion criteria: 1.Previous history of transient ischemic attack (TIA) or clinically overt cerebrovascular accident (CVA) (ischemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy 2.Findings on TCD: Current or previous values for time averaged mean of the maximum velocity (TAMMV) that are Conditional or Abnormal*. Conditional TAMMV values are =153 cm/sec using imaging TCD (TCDi) technique (corresponding to =170 cm/sec by the non-imaging technique). Both the middle cerebral artery and the internal carotid artery should be considered. Abnormal TAMMV values are =180 cm/sec using TCDi (corresponding to =200 cm/sec by the non-imaging technique) and are an indication for chronic transfusions because of a high stroke risk. Any other criteria that would locally be considered as TCD indications for chronic transfusion would also exclude the patient. 3.Undergoing treatment with chronic RBC transfusion therapy 4.Use of non-steroidal anti-inflammatory drugs (NSAIDs) >3 days per week 5.Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued. 6.Moderate or severe hepatic impairment, defined as Child-Pugh Class B or C,or renal failure requiring dialysis 7.Active pathological bleeding or increased risk of bleeding complications according to Investigator 8.Risk of bradycardic events (known sick sinus syndrome or second or third degree atrioventricular block) 9.Concomitant oral or intravenous therapy with strong CYP3A4 inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers 10.Surgical procedure planned to occur during the study 11.Patients who are currently pregnant or breastfeeding, or planning to become pregnant during the study 12.Known hypersensitivity or contraindication to ticagrelor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterise the relationship between ticagrelor dose and inhibition of platelet aggregation in paediatric patients with Sickle Cell Disease (SCD), using PK-PD modelling, to support dose selection for Phase III; Secondary Objective: To determine the PK properties of ticagrelor in paediatric patients with Sickle Cell Disease (SCD) and to assess impact of weight, age and other demographic on the ticagrelor pharmacokinetics Investigation of efficacy of ticagrelor vs. placebo in paediatric patients with SCD in reducing: Number of Vaso-occlusive crises (VOC) Days hospitalized for VOC or other complications of SCD Days with pain (ages =4 years only) Intensity of pain (ages =4 years only) Days of analgesic use (ages =4 years only) Days of opioid analgesic use Days of absence from school or work (ages =6 years only) To assess safety and tolerability of single and multiple doses of ticagrelor in paediatric patients with SCD To determine the percent of patients with haemorrhagic events requiring medical intervention. ;Primary end point(s): P2Y12 reaction units (PRU), Maximum plasma concentration (Cmax), Area under the plasma concentration time curve (AUC); Timepoint(s) of evaluation of this end point: PRU:Pre-dose, 2, 6 h post-dose at Visit 2 and 3 (after single dosing); Pre-dose, 2h post-dose at Visit 4 (after repeated dosing) Cmax and AUC: Visits 2,3, and 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Concentrations of Ticagrelor an its active metabolite Efficacy endpoints: number of Vaso-occlusive crises, number of Vaso-occlusive crises requiring hospitalization or emergency department visits, days hospitalized for complications of sickle cell disease, days with pain, intensity of pain, days of analgesic use, days of opioid analgesic use, days of absence from school or work Safety endpoints: AEs/Serious Adverse Events (SAE)s, Vital signs, laboratory safety samples, Haemorrhagic events ; Timepoint(s) of evaluation of this end point: Ticagrelor concentration: 1, 2, 4, 6 h post-dose at Visit 2 and 3 (after single dosing); Pre-dose, 1, 2h post-dose at Visit 4 (after repeated dosing). Efficacy endpoints: during 4 weeks of study treatment starting from randomization in Part B. Safety endpoints: vital signs at all study visits (1-9), laboratory samples at Visits 1, 4 and 9, SAEs from enrollment until Visit 9 and AEs, haemorrhagic events from randomization (Visit 2) until Visit 9. | — |
Countries
Canada, Egypt, Ghana, Italy, Kenya, Lebanon, South Africa, Turkey, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed