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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- P2Y12 Reaction Units (PRU) - Part B
研究概览
简要总结
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
详细描述
This is a multicenter, open-label, dose-ranging study of ticagrelor followed by a double blind, placebo-controlled extension phase in paediatric patients with sickle cell disease (SCD).
Part A: Patients will be randomised 1:1 to receive one of two dosing schedules consisting of two single weight-adjusted doses of ticagrelor. Pharmacokinetic (PK) parameters and pharmacodynamic (PD) measurements will be determined following each dose. Platelet aggregation will be measured using the VerifyNow™ P2Y12 assay.
Following these 2 single doses, all patients will receive open-label one-week treatment with ticagrelor twice daily to determine tolerability prior to randomisation into Part B.
Part B: In this part patients will be randomised (2:1 ratio) to ticagrelor twice daily or placebo for a 4-week treatment phase.
During the study, patients will be followed for the occurrence of vaso-occlusive crisis (VOC) and for other disease manifestations such as daily pain, analgesic use and complications of SCD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ticagrelor Dose 1a + Dose 2a
Part A: Ticagrelor Dose 1a and ticagrelor Dose 2a single doses + 1 week repeated dosing Part B: Ticagrelor or placebo 4 weeks repeated dosing.
干预措施: Ticagrelor Dose 1a + Dose 2a (Drug)
Ticagrelor Dose 1b + Dose 2b
Part A: Ticagrelor Dose 1b and ticagrelor Dose 2b single doses + 1 week repeated dosing. Part B: Ticagrelor or placebo 4 weeks repeated dosing.
干预措施: Ticagrelor Dose 1b + Dose 2b (Drug)
结局指标
主要结局
P2Y12 Reaction Units (PRU) - Part B
时间窗: PRU measurements are taken after 4 weeks of double blind treatment at the end of Part B.
P2Y12 Reaction Units (PRU) - Part A
时间窗: 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 A
时间窗: 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 B
时间窗: 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
时间窗: 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).
The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
Area Under the Plasma Concentration Time Curve (AUC) - Part B
时间窗: PK measurements (up to 4 hours post-dose) are taken after 4 weeks of double blind treatment at the end of Part B.
The PK parameter presented was derived using a model based analysis and not from a non-compartmental (NCA) analysis.
次要结局
- 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).)
- 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).)
- 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).)
- 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.)
- 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))
- 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).)
- Assessment of AR-C124910XX 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))
- Assessment of AR-C124910XX 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.)
- Oral Clearance (CL/F) - 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).)
- Oral Clearance (CL/F) - 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.)
- 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).)
- Percentage of Days With Pain (Age >=4) - Part B(During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).)
- Mean Intensity of Pain (Age >=4) - Part B(During 4 weeks of study treatment starting from randomization in Part B (week 2) up to 4 weeks (week 6).)
- 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).)