A pharmacokinetic (PK) and pharmacodynamic (PD) dose-ranging Phase II study of ticagrelor followed by a 4 weeks extension phase in paediatric patients with sickle cell disease

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2014-001006-18-GB
• Date of registration: 18/06/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A pharmacokinetic (PK) and pharmacodynamic (PD) dose-ranging Phase II study of ticagrelor followed by a 4 weeks extension phase in paediatric patients with sickle cell disease
• Scientific title: Multicenter, open-label, randomised, pharmacokinetic (PK) and pharmacodynamic (PD) dose-ranging Phase II study of ticagrelor followed by a double-blind, randomised, parallel-group, placebo-controlled 4 weeks extension phase in paediatric patients with sickle cell disease
• Date of first enrolment: 27/08/2014
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001006-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Part A is open label and Part B is double blind part; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Egypt, Ghana, Italy, Kenya, Lebanon, South Africa, Turkey, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: AstraZeneca

• Name: Information Center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
1.Children aged =2 to <18 years of age and body weight >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:
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Product Name: ticagrelor
Product Code: AZD6140
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: ticagrelor
CAS Number: 274693-27-5
Current Sponsor code: AZD6140
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Granules for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): P2Y12 reaction units (PRU), Maximum plasma concentration (Cmax), Area under the plasma concentration time curve (AUC)

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.

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 Outcome(s)

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.

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

Secondary ID(s)

D5136C00007

NCT02214121

Source(s) of Monetary Support

AstraZenenca AB

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 29/07/2017
• Date Completed: 27/02/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001006-18/results