The purpose of this study was to determine the appropriate dosing regimen of fosaprepitant, when administered with ondansetron (with or without dexamethasone), for the prevention of CINV in children from birth to \<17 years of age. Fosaprepitant is a prodrug to aprepitant. All participants who completed the randomized Cycle 1 could elect to receive open-label fosaprepitant during optional Cycles 2-6.
Under Amendment 01, 0517-029 enrolled participants in the following age cohorts: 2-\<6, 6-\<12 and 12-17 years old. The study was randomized, partially-blinded, with parallel group assignment. Participants were randomized to one of three fosaprepitant doses or the control group. (Amendment 02 and Amendment 03 were country-specific amendments in Brazil that were required as per local regulations with no change in study design.) Under Amendment 04, the 12-17 year-old cohort was closed since that cohort fully enrolled. An additional fosaprepitant dose was added and all participants were allocated to this one treatment group. Amendment 04 was open-label and enrolled participants in the following age cohorts: 0-\<2, 2-\<6 and 6-\<12 years old.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
240
Administered intravenously (IV) as a single dose
Administered IV as a single dose
Administered IV according to local labeling and/or local standard of care
Administered IV according to local labeling and/or local standard of care
Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Area Under the Concentration-time Curve of Aprepitant From Time 0 to 24 Hours (AUC 0-24hr) in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Cmax of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Tmax of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
t1/2 of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
C24hr of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
C48hr of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
CL/F of Aprepitant in Participants 2 to <6 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Cmax of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Tmax of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
t1/2 of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
C24hr of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
C48hr of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
CL/F of Aprepitant in Participants 6 to <12 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Cmax of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Tmax of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
C24hr of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
C48hr of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
CL/F of Aprepitant in Participants 12 to 17 Years of Age
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Time frame: Up to 14 days postdose in Cycle 1
Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Time frame: Up to 14 days postdose for each cycle (Cycles 2-6)
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