A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02214121
• Date of registration: 08/08/2014
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: A Pharmacokinetic (PK) and Pharmacodynamic (PD) Dose-ranging Phase II Study of Ticagrelor in Paediatric Patients With Sickle Cell Disease HESTIA 1
• 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: September 11, 2014
• Target sample size: 46
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02214121
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

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

Key inclusion & exclusion criteria

Inclusion criteria

- Children aged =2 to <18 years of age

- Diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassaemia (HbS/ß0)

Exclusion criteria

- At risk for haemorrhagic or bradycardic events

- Significant hepatic impairment

- Renal failure requiring dialysis

- Concomitant oral or intravenous therapy with strong CYP3A4 (cytochrome) inhibitors,
CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers.

- Surgical procedure planned to occur during the study.

- Patients who are currently pregnant or breastfeeding or planning to become pregnant
during the study.

- Patients who have known hypersensitivity or contraindication to ticagrelor.



Age minimum: 2 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease

Intervention(s)

Drug: Ticagrelor Dose 1a + Dose 2a

Drug: Ticagrelor Dose 1b + Dose 2b

Primary Outcome(s)

Area Under the Plasma Concentration Time Curve (AUC) - Part B [Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.]

P2Y12 Reaction Units (PRU) - Part A [Time Frame: PRU measurements are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14). Up to 8 hours post-dose (6 hours following protocol amendment) Visit 2 and 3, and up to 2 hours Visit 4.]

Maximum Plasma Concentration (Cmax) - Part B [Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.]

Area Under the Plasma Concentration Time Curve (AUC) - Part A [Time Frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).]

Maximum Plasma Concentration (Cmax) - Part A [Time Frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).]

P2Y12 Reaction Units (PRU) - Part B [Time Frame: PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.]

Secondary Outcome(s)

Assessment of AR-C124910XX Concentration - Part A [Time Frame: In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)]

Assessment of AR-C124910XX Concentration - Part B [Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.]

Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Oral Clearance (CL/F) - Part B [Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.]

Percentage of Days of Absence From School or Work (Age >=6) - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Number of Vaso-occlusive Crises - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Oral Clearance (CL/F) - Part A [Time Frame: PK measurements (up to 8 hours post-dose) are taken in conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7) and after repeated dosing at Visit 4 (Day 14).]

Percentage of Days With Pain (Age >=4) - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Assessment of Ticagrelor Concentration - Part A [Time Frame: In conjunction with single doses at Visit 2 (Day 0) and Visit 3 (Day 7), after repeated dosing at Visit 4 (Day 14). Up to 8h post-dose (6h following protocol amendment, no pre-dose) Visit 2 and 3, up to 2h Visit 4 (pre-dose, 1h added following amendment)]

Percentage of Days of Analgesic Use (Age >= 4) - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Assessment of Ticagrelor Concentration - Part B [Time Frame: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.]

Mean Intensity of Pain (Age >=4) - Part B [Time Frame: During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).]

Secondary ID(s)

2014-001006-18

D5136C00007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/05/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02214121