NCT03492931已完成1 期
A Multi-centre, Phase I, Open-label, Single-dose Study to Investigate Pharmacokinetics (PK) of Ticagrelor in Infants and Toddlers, Aged 0 to Less Than 24 Months, With Sickle Cell Disease (HESTIA4)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Peak Plasma Concentration (Cmax) of Ticagrelor
研究概览
简要总结
The purpose of this Phase I study is to investigate the pharmacokinetic properties of ticagrelor in pediatric patients from 0 to less than 24 months with sickle cell disease.
Ticagrelor dose level adjustment will require a Protocol amendment and regulatory approval.
详细描述
Study design This Phase I paediatric study (in patients aged 0 to <24 months) with ticagrelor is planned to be a multi-centre, open-label, single dose study.
Primary Objective:
To determine the PK properties of ticagrelor after a single oral dose
Secondary Objectives:
To determine the PK properties of the active metabolite (AR-C124910XX) after a single oral dose To assess the acceptability and the palatability of a single oral dose of ticagrelor
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
盲法说明
Study has an Open-Label design.
入排标准
- 年龄范围
- 1 Day 至 23 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Paediatric patients aged <24 months, diagnosed with homozygous sickle cell (HbSS) or sickle beta-zero-thalassemia (HbS/β0), as confirmed by high performance liquid chromatography or haemoglobin electrophoresis.
- •Body weight ≥5 kg at the time of screening.
- •If treated with an anti-sickling agent such as hydroxyurea, the weight-adjusted dose must be stable for 3 months before screening/enrolment.
- •Provision of signed and dated written informed consent from parents/legal guardians prior to any study specific procedures not part of standard medical care.
- •Exclusion criteria
- •History of transient ischaemic attack or cerebrovascular event/accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy.
- •Significantly underdeveloped with regards to height, weight or head circumference for age, as judged by the Investigator.
- •Severe developmental delay (eg, cerebral palsy or mental retardation).
- •Receiving chronic treatment (>3 days/week) with non-steroidal anti-inflammatory drugs (NSAIDs).
- •Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
- •Moderate or severe hepatic impairment, defined as laboratory values of alanine aminotransferase (ALT) >2 × upper limit of normal (ULN), total bilirubin >2 × ULN (unless judged by the Investigator to be caused by haemolysis), albumin <35 g/L and international normalised ratio (INR) >1.4, or symptoms of liver disease (eg, ascites).
- •Renal failure requiring dialysis.
- •Active pathological bleeding or increased risk of bleeding complications according to the Investigator.
- •Haemoglobin <6 g/dL from test performed at Screening (Visit 1).
- •Platelets <100 × 10^9/L from test performed at Screening (Visit 1).
- •Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second or third degree atrioventricular block).
- •Concomitant oral or intravenous therapy with moderate or strong CYP3A4 inhibitors, CYP3A4 substrates with narrow therapeutic indices, or strong CYP3A4 inducers that have not been stopped at least 5 half-lives before dose administration.
- •Patient breastfed by mother who is under treatment of strong CYP3A4 inhibitors,
- •Active untreated malaria. Patients with suspected malaria at Screening (Visit 1) will be tested.
- •Surgical procedure planned to occur during the study including 5 days after ticagrelor administration.
- •Known hypersensitivity or contraindication to ticagrelor.
- •Concern for the inability of the patient or parents to comply with study procedures and/or follow-up.
- •Any condition which, in the opinion of the Investigator, would make it unsafe or unsuitable for the patient to participate in this study.
- •Previously administered ticagrelor in the present study.
- •Participation in another clinical study with an investigational medicinal product (IMP) or device during the last 30 days preceding screening/enrolment.
- •Involvement of member of patient's family in planning and/or conduct of the study (applies to both AstraZeneca personnel and personnel at study centre).
排除标准
- 未提供
研究组 & 干预措施
Treatment arm
Experimental
Single dose of ticagrelor based on age
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Peak Plasma Concentration (Cmax) of Ticagrelor
时间窗: 1,2,4,6 hours post dose
This measure is obtained from observed plasma concentrations
Area under plasma concentration curve
时间窗: 1,2,4,6 hours post dose
This measure is obtained from the population PK analysis
CL/F (Oral clearance)
时间窗: 1,2,4,6 hours post dose
This measure is obtained from the population PK analysis.
次要结局
- Peak Plasma Concentration (Cmax) for active metabolite (AR-C124910XX)(1,2,4,6 hours post dose)
- Area under plasma concentration curve(1,2,4,6 hours post dose)
- Assessment of ticagrelor suspension for palatability(Day 1, single timepoint assessment)
研究者
研究点 (1)
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