A Multicenter, Open-Label, 5-Part Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Aprepitant and Fosaprepitant Dimeglumine in Pediatric Patients Receiving Emetogenic Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 92
- 主要终点
- Time to Cmax (Tmax) for Aprepitant
研究概览
简要总结
This study will determine the appropriate dosing regimen of aprepitant and fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric participants from 0 months to 17 years of age.
详细描述
Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after intravenous administration; the pharmacological effect of fosaprepitant is attributed to aprepitant. The birth to one year old cohort will be initiated in Parts III and IV upon completion of Part II (Steps A and B) in participants <6 months of age.
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is 0 (at least 37 weeks gestation) to 17 years of age
- •Is scheduled to receive moderately to highly nausea-inducing chemotherapy or participant did not tolerate a previous chemotherapy regimen that is planned to be repeated
- •Is expected to receive ondansetron
- •Female participants who have begun menstruating must have a negative pregnancy test
- •Weighs ≥3.0 kg if <6 months of age, ≥6.0 kg if >6 months of age, and ≥7.5 kg if > 2 years of age
- •Has a pre-existing venous catheter
排除标准
- •Uses any illicit drugs or abuses alcohol
- •Is pregnant or breast feeding
- •Has a symptomatic central nervous system (CNS) tumor
- •Has an infection or other uncontrolled disease other than cancer
- •Has known history of heart QT wave prolongation
研究组 & 干预措施
Part IA-fosaprepitant 115 mg/aprepitant
Day 1, fosaprepitant intravenous (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Ondansetron (Drug)
Part IA-fosaprepitant 115 mg/aprepitant
Day 1, fosaprepitant intravenous (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Dexamethasone (Drug)
Part IB-fosaprepitant 150 mg
Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Ondansetron (Drug)
Part IB-fosaprepitant 150 mg
Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Dexamethasone (Drug)
Part IIA-aprepitant 80 mg equiv.
Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Ondansetron (Drug)
Part IIA-aprepitant 80 mg equiv.
Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Dexamethasone (Drug)
Part IIB-aprepitant 125 mg equiv.
Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Ondansetron (Drug)
Part IIB-aprepitant 125 mg equiv.
Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Dexamethasone (Drug)
Part III-ondansetron
Ondansetron administered IV per local standard of care on Days 1, 2, and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethasone is optional with the exception of the birth to one year old cohort.
干预措施: Dexamethasone (Drug)
Part IV-aprepitant regimen
Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; Birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; Birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to one year old cohort.
干预措施: Ondansetron (Drug)
Part IV-aprepitant regimen
Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; Birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; Birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to one year old cohort.
干预措施: Dexamethasone (Drug)
Part V-fosaprepitant regimen
Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Ondansetron (Drug)
Part V-fosaprepitant regimen
Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Time to Cmax (Tmax) for Aprepitant
时间窗: Up to 72 hours post fosaprepitant/aprepitant dose
Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Cmax for Fosaprepitant
时间窗: Up to 72 hours post fosaprepitant dose
Cmax is a measure of the maximum amount of fosaprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant
时间窗: Up to 24 hours post fosaprepitant/aprepitant dose
AUC is a measure of the amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for pharmacokinetic (PK) assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hours (hr) post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy.
Maximum Plasma Concentration (Cmax) for Aprepitant
时间窗: Up to 72 hours post fosaprepitant/aprepitant dose
Cmax is a measure of the maximum amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Apparent Terminal Half-life (t1/2) for Aprepitant
时间窗: Up to 72 hours post fosaprepitant/aprepitant dose
t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Tmax for Fosaprepitant
时间窗: Up to 72 hours post fosaprepitant dose
Tmax is a measure of the amount of time after dosing to when the maximum concentration of fosaprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Number of Participants Discontinuing Study Drug Due to an AE
时间窗: Day 1 up to Day 3
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. The number of participants who discontinued from the study due to an AE are summarized.
Number of Participants Experiencing Adverse Events (AEs)
时间窗: Up to 14 days after last dose of study drug (Up to 17 days)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for the occurrence AEs for up to 14 days after last dose of study drug.
次要结局
- Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age(Up to 24 hours post dexamethasone dose)