An Open-Label, Dose-Ranging Study of Prasugrel in Pediatric Patients With Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
研究概览
简要总结
The purpose of this study is to determine the correct prasugrel dosage to be given to children with sickle cell disease (SCD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Are male or female with SCD [(homozygous sickle cell (HbSS) and hemoglobin S beta ^0 thalassemia (HbS β^0 thalassemia)]
- •Have a body weight ≥12 kilograms (kg) and are ≥2 to <18 years of age at the time of screening
- •If participants are ≥2 and ≤16 years of age, have had a transcranial Doppler within the last year
- •Participants on hydroxyurea must be on a stable dose for the 60 days prior to enrollment without signs of hematologic toxicity at screening
- •Have a legal representative that is in competent mental condition to provide written informed consent on behalf of the study participant before entering the study. The child may be required to give documented assent, if required by local regulations.
- •If sexually active, has a negative pregnancy test at screening (if female) and agrees to use a reliable method of birth control during the study (for both males and females)
排除标准
- •Known to have hemoglobin C sickle cell (HbSC) or hemoglobin S beta ^plus thalassemia (HbS β^+ thalassemia) genotypes
- •Vaso-occlusive crisis (VOC) requiring medical attention within 15 days prior to screening
- •Have a concomitant medical illness (for example, terminal malignancy) that in the opinion of the investigator is associated with reduced survival
- •Hepatic dysfunction characterized by alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN)
- •Renal dysfunction requiring chronic dialysis or creatinine ≥ 1.5 milligrams per deciliter (mg/dL)
- •Contraindication for antiplatelet therapy
- •History of intolerance or allergy to approved thienopyridines (clopidogrel, ticlopidine, or prasugrel)
- •Participants with a hematocrit <18%
- •History of abnormal or conditional transcranial Doppler [velocity in middle cerebral or carotid artery ≥170 centimeters per second (cm/sec)] within the last year
- •Any history of bleeding diathesis
- •Any history of renal papillary necrosis
- •Active internal bleeding
- •History of spontaneous gastrointestinal bleeding
- •Gross hematuria or > 300 red blood cells (RBC)/high-powered field (HPF) on urinalysis at the time of screening
- •Any history of vitreous hemorrhage
- •Prior history of hemorrhagic or ischemic stroke, a transient ischemic attack (TIA), or other intracranial hemorrhage
- •Have clinical findings, in the judgment of the investigator, associated with an increased risk of bleeding
- •Platelet count <100,000 per microliter (μl) of blood
- •Have had recent surgery (within 30 days prior to screening) or are scheduled to undergo surgery within the next 60 days
- •History of dysfunctional uteral bleeding, in the judgment of the investigator
- •Treatment with packed RBC or whole blood transfusion therapy within 30 days prior to dosing
- •Any nonsteroidal anti-inflammatory drug (NSAID) use within 5 days prior to screening
- •Any aspirin, warfarin, thienopyridine, or other antiplatelet medication use within 10 days prior to dosing
- •Anticipated use of aspirin, warfarin, thienopyridine, or other antiplatelet medication during the study period
研究组 & 干预措施
Part A: Prasugrel Single Dose
Prasugrel 0.03 milligrams per kilogram (mg/kg) to 0.60 mg/kg dosage to be titrated up or down based on desired platelet inhibition, administered orally [oral-disintegrating tablet (ODT)], single dose given up to 3 occasions, at different strengths, with up to 18 days between doses.
干预措施: Prasugrel (Drug)
Part B: Prasugrel Once-Daily Dose
Daily prasugrel dose (mg/kg) that is expected to achieve mean platelet activation inhibition of 30% administered orally, once daily for 10-18 days and then followed by prasugrel dose (mg/kg) that is expected to achieve mean platelet activation inhibition of 50% administered orally, once daily for 10-18 days, for a total of 20-36 days.
干预措施: Prasugrel (Drug)
结局指标
主要结局
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Active Metabolite (Pras-AM)
时间窗: Parts A and B: 0.5, 1, 1.5, 2, 4 hours postdose
AUC of Pras-AM from time 0 up to the last sampling time of 4 hours postdose \[AUC(0-tlast)\] is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and is reported for doses administered on site (0.06, 0.08, and 0.12 mg/kg) during Part B (once-daily repeated dosing phase) of the study. Four participants received the same dose at multiple visits where pharmacokinetic samples were collected.
Percentage of Platelet Inhibition as Measured by VerifyNow™P2Y12 (VN)
时间窗: Part A: 4 hours postdose and Part B: at steady state (14 ± 4 days after the start of each new dosage)
Accumetrics VN assay: A point-of-care device that measures platelet aggregation. Percentage of platelet inhibition is reported by dose administered \[0.03, 0.05, 0.07, 0.09, 0.11, 0.13, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, and 0.6 milligrams per kilogram (mg/kg)\] during Part A (single-dose range finding phase) and also during the once-daily repeated dosing phase in Part B, at steady state, 14 ± 4 days after each new dose (0.06, 0.08, and 0.12 mg/kg) is administered. One participant received the same dose at multiple visits (Part A) and one participant received the same daily dose during both dosing periods in Part B.
次要结局
- Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Prasugrel Inactive Metabolite(Part A: 0.5, 1, 1.5, 2, 4 hours postdose)
- Number of Participants With Pain(Part B: Baseline and Day14 ± 4 days postdose in each dosing period)
- Number of Participants With Hemorrhagic Events Requiring Medical Intervention(Part B: Baseline up to Day 36)