A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134)
- Conditions
- Chemotherapy-Induced Nausea and Vomiting
- Interventions
- Registration Number
- NCT00818259
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 92
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part IIA-aprepitant 80 mg equiv. Dexamethasone 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. Part III-ondansetron Dexamethasone 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. Part IA-fosaprepitant 115 mg/aprepitant Ondansetron 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. Part IA-fosaprepitant 115 mg/aprepitant Dexamethasone 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. Part IB-fosaprepitant 150 mg Ondansetron 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. Part IB-fosaprepitant 150 mg Dexamethasone 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. Part IIA-aprepitant 80 mg equiv. Ondansetron 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. Part IIB-aprepitant 125 mg equiv. Ondansetron 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. Part IIB-aprepitant 125 mg equiv. Dexamethasone 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. Part IV-aprepitant regimen Ondansetron 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. Part IV-aprepitant regimen Dexamethasone 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. Part V-fosaprepitant regimen Ondansetron 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. Part V-fosaprepitant regimen Dexamethasone 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.
- Primary Outcome Measures
Name Time Method Time to Cmax (Tmax) for Aprepitant 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 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 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.
Tmax for Fosaprepitant 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 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.
Maximum Plasma Concentration (Cmax) for Aprepitant 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 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.
Number of Participants Experiencing Adverse Events (AEs) 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.
- Secondary Outcome Measures
Name Time Method Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age Up to 24 hours post dexamethasone dose Blood samples for PK assessment were to be collected at the following time points: Parts II and V - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts III and IV - Immediately after infusion of dexamethsone and 0.5, 1.5, 3, 8 and 24 hr post start of chemotherapy.