Investigation of Platelet Aggregation in Paediatric Patients With Sickle Cell Disease Clinical Trial
— HESTIA 1Official 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
| Verified date | November 2018 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this Phase II dose-ranging study is to investigate pharmacokinetic (PK) and pharmacodynamic (PD) properties of various doses of ticagrelor followed by 4 weeks of twice-daily treatment in paediatric patients with sickle cell disease
| Status | Completed |
| Enrollment | 46 |
| Est. completion date | February 27, 2017 |
| Est. primary completion date | February 27, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 17 Years |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Research Site | Toronto | Ontario |
| Kenya | Research Site | Kisian | |
| Kenya | Research Site | Nairobi | |
| Lebanon | Research Site | Beirut | |
| Lebanon | Research Site | Beirut | |
| Lebanon | Research Site | Tripoli | |
| South Africa | Research Site | Parow | |
| South Africa | Research Site | Rondebosch | |
| United Kingdom | Research Site | Cardiff | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | Manchester | |
| United States | Research Site | Charleston | South Carolina |
| United States | Research Site | Chicago | Illinois |
| United States | Research Site | Detroit | Michigan |
| United States | Research Site | Hershey | Pennsylvania |
| United States | Research Site | Orange | California |
| United States | Research Site | Philadelphia | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca |
United States, Canada, Kenya, Lebanon, South Africa, United Kingdom,
Hsu LL, Sarnaik S, Williams S, Amilon C, Wissmar J, Berggren A; HESTIA1 Investigators. A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell disease: A 2-part phase 2 study. Am J Hematol. 2018 Dec;93(12):1493-1500. doi: 10.1002/ajh.25273. Epub 2018 Oct 2. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Haemorrhagic Events - Part A | From randomisation to Part A (week 0) through Visit 4 (week 2) | ||
| Other | Haemorrhagic Events - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | ||
| Primary | P2Y12 Reaction Units (PRU) - Part A | 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. | ||
| Primary | P2Y12 Reaction Units (PRU) - Part B | PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B. | ||
| Primary | Maximum Plasma Concentration (Cmax) - Part A | 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). | ||
| Primary | Maximum Plasma Concentration (Cmax) - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | ||
| Primary | Area Under the Plasma Concentration Time Curve (AUC) - Part A | The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis. | 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). | |
| Primary | Area Under the Plasma Concentration Time Curve (AUC) - Part B | The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis. | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | |
| Secondary | Assessment of Ticagrelor Concentration - Part A | 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) | ||
| Secondary | Assessment of Ticagrelor Concentration - Part B | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | ||
| Secondary | Assessment of AR-C124910XX Concentration - Part A | AR-C124910XX is the active metabolite of Ticagrelor | 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) | |
| Secondary | Assessment of AR-C124910XX Concentration - Part B | AR-C124910XX is the active metabolite of Ticagrelor | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | |
| Secondary | Oral Clearance (CL/F) - Part A | The PK parameter presented were derived using a model based analysis and not from a non-compartmental (NCA) analysis. | 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). | |
| Secondary | Oral Clearance (CL/F) - Part B | The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis. | PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B. | |
| Secondary | Number of Vaso-occlusive Crises - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | ||
| Secondary | Number of Vaso-occlusive Crises Requiring Hospitalization or Emergency Department Visits - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | ||
| Secondary | Percentage of Days Hospitalized for Vaso-occlusice Crisis or Other Complications of Sickle Cell Disease - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | ||
| Secondary | Percentage of Days With Pain (Age >=4) - Part B | Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | |
| Secondary | Mean Intensity of Pain (Age >=4) - Part B | Pain measured using the Faces Pain Scale, range 0-10 (0, 2, 4, 6, 8, 10), where 0 is no pain | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | |
| Secondary | Percentage of Days of Analgesic Use (Age >= 4) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | ||
| Secondary | Percentage of Days of Opioid Analgesic Use (Age >=4) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). | ||
| Secondary | Percentage of Days of Absence From School or Work (Age >=6) - Part B | During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6). |