Chemotherapy-induced Nausea and Vomiting
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGFosaprepitant
Administered intravenously (IV) as a single dose
Administered IV as a single dose
DRUGOndansetron
Administered IV according to local labeling and/or local standard of care
DRUG5-hydroxytryptamine 3 antagonist
Administered IV according to local labeling and/or local standard of care
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Is 0 months (at least 37 weeks gestation) to \<18 years of age * Scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting * Expected to receive ondansetron as part of antiemetic regimen (Cycle 1); Expected to receive a 5-HT3 antagonist as part of antiemetic regimen (Cycles 2-6) * If female and has begun menstruating, must have a negative pregnancy test prior to study participation and agree to remain abstinent or use a barrier form of contraception * Predicted life expectancy of ≥3 months * Pre-existing functioning central venous catheter * Weight ≥3rd percentile for age and gender (and ≥3.0 kg)
Exclusion criteria
* Vomited in the 24 hours prior study drug administration (Cycle 1) * Current user of any illicit drugs (including marijuana) or current evidence of alcohol abuse * Scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy * Received or will receive radiation therapy to the abdomen or pelvis in the week prior to study drug administration and/or during the course of the study * Pregnant or breast feeding * Allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist * Has a symptomatic central nervous system (CNS) tumor causing nausea and/or vomiting * Has an active infection, congestive heart failure, slow heart rate, or other uncontrolled disease other than cancer * Mentally incapacitated or has a significant emotional or psychiatric disorder * Known history of QT prolongation or is taking any medication known to lead to QT prolongation * Taking other excluded medications * Participated in any previous study of aprepitant or fosaprepitant, or taken an investigational drug within 4 weeks prior to study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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 to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| 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 | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age | Approximately 24 hours (from 23 to 25 hours) post-infusion | 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. |
| Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age | Approximately 48 hours (from 46 to 50 hours) post-infusion | 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. |
| Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Cmax of Aprepitant in Participants 2 to <6 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Tmax of Aprepitant in Participants 2 to <6 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| t1/2 of Aprepitant in Participants 2 to <6 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| C24hr of Aprepitant in Participants 2 to <6 Years of Age | Approximately 24 hours (from 23 to 25 hours) post-infusion | 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. |
| C48hr of Aprepitant in Participants 2 to <6 Years of Age | Approximately 48 hours (from 46 to 50 hours) post-infusion | 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. |
| CL/F of Aprepitant in Participants 2 to <6 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Cmax of Aprepitant in Participants 6 to <12 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Tmax of Aprepitant in Participants 6 to <12 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| t1/2 of Aprepitant in Participants 6 to <12 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| C24hr of Aprepitant in Participants 6 to <12 Years of Age | Approximately 24 hours (from 23 to 25 hours) post-infusion | 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. |
| C48hr of Aprepitant in Participants 6 to <12 Years of Age | Approximately 48 hours (from 46 to 50 hours) post-infusion | 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. |
| CL/F of Aprepitant in Participants 6 to <12 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Cmax of Aprepitant in Participants 12 to 17 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Tmax of Aprepitant in Participants 12 to 17 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| C24hr of Aprepitant in Participants 12 to 17 Years of Age | Approximately 24 hours (from 23 to 25 hours) post-infusion | 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. |
| C48hr of Aprepitant in Participants 12 to 17 Years of Age | Approximately 48 hours (from 46 to 50 hours) post-infusion | 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. |
| CL/F of Aprepitant in Participants 12 to 17 Years of Age | Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion | 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. |
| Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 | Up to 14 days postdose 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. |
| Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6 | Up to 14 days postdose for each cycle (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. |
Participant flow
Recruitment details
This study enrolled participants scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days and were expected to receive ondansetron as part of their antiemetic regimen. Additional inclusion and exclusion criteria applied.
Pre-assignment details
Participants (2 to \<6, 6 to \<12 and 12 to17 years-old) were enrolled in a randomized, partially-blinded study of 4 doses of fosaprepitant and a control in Cycle 1. Participants (0 to \<2, 2 to \<6 and 6 to \<12 years-old) were invited to participate in optional Cycles 2-6 which was an open-label study of 2 doses of fosaprepitant.
Participants by arm
| Arm | Count |
|---|---|
| Fosaprepitant 5 mg/Kg-Cycle 1 Participants were administered intravenous (IV) fosaprepitant at the following weight-adjusted doses: participants 4 months to \<12 years old were administered 5 mg/kg (not to exceed 150 mg); participants 1 to \<4 months old were administered 2.5 mg/kg; participants 0 to \<1 month old were administered 1.25 mg/kg. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone. | 74 |
| Fosaprepitant 3 mg/Kg-Cycle 1 Participants 12 to 17 years old were administered 150 mg IV fosaprepitant. Participants 2 to \<12 years old were administered a weight-adjusted dose of 3 mg/kg (not to exceed 150 mg). Participants were also administered IV ondansetron 0.15 mg/kg x 3 doses with or without dexamethasone. | 43 |
| Fosaprepitant 1.2 mg/Kg-Cycle 1 Participants 12 to 17 years old were administered 60 mg IV fosaprepitant. Participants 2 to \<12 years old were administered a weight-adjusted dose of 1.2 mg/kg (not to exceed 60 mg). Participants were also administered IV ondansetron 0.15 mg/kg x 3 doses with or without dexamethasone. | 44 |
| Fosaprepitant 0.4 mg/Kg-Cycle 1 Participants 12 to 17 years old were administered 20 mg IV fosaprepitant. Participants 2 to \<12 years old were administered a weight-adjusted dose of 0.4 mg/kg (not to exceed 20 mg). Participants were also administered IV ondansetron 0.15 mg/kg x 3 doses with or without dexamethasone. | 41 |
| Placebo Control-Cycle 1 Participants were administered IV normal saline at volume to match age and weight specific doses of fosaprepitant. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children \<6 months of age), with or without dexamethasone. | 38 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Base Study-Cycle 1 | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Base Study-Cycle 1 | Consent Withdrawn by Participant | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Base Study-Cycle 1 | Protocol Violation | 0 | 0 | 0 | 0 | 3 | 0 | 0 |
| Base Study-Cycle 1 | Technical Problems | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Base Study-Cycle 1 | Withdrawal by Parent/Guardian | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Optional Extension-Cycles 2-6 | Completed Chemotherapy Regimen | 0 | 0 | 0 | 0 | 0 | 15 | 24 |
| Optional Extension-Cycles 2-6 | Consent Withdrawn by Participant | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Optional Extension-Cycles 2-6 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Optional Extension-Cycles 2-6 | Did Not Meet Cycle Eligibility Criteria | 0 | 0 | 0 | 0 | 0 | 4 | 11 |
| Optional Extension-Cycles 2-6 | Did Not Respond To Chemotherapy Regimen | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Optional Extension-Cycles 2-6 | Excluded Medication | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Optional Extension-Cycles 2-6 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Optional Extension-Cycles 2-6 | Non-compliance With Protocol | 0 | 0 | 0 | 0 | 0 | 6 | 4 |
| Optional Extension-Cycles 2-6 | Participant Moved | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Optional Extension-Cycles 2-6 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 7 | 11 |
| Optional Extension-Cycles 2-6 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| Optional Extension-Cycles 2-6 | Technical Problems | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Optional Extension-Cycles 2-6 | Withdrawal by Parent/Guardian | 0 | 0 | 0 | 0 | 0 | 1 | 5 |
Baseline characteristics
| Characteristic | Fosaprepitant 5 mg/Kg-Cycle 1 | Fosaprepitant 3 mg/Kg-Cycle 1 | Fosaprepitant 1.2 mg/Kg-Cycle 1 | Fosaprepitant 0.4 mg/Kg-Cycle 1 | Placebo Control-Cycle 1 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.2 Months STANDARD_DEVIATION 42.3 | 123.8 Months STANDARD_DEVIATION 51.3 | 119.4 Months STANDARD_DEVIATION 52.7 | 119.2 Months STANDARD_DEVIATION 54.3 | 122.5 Months STANDARD_DEVIATION 54 | 102.4 Months STANDARD_DEVIATION 57 |
| Sex: Female, Male Female | 32 Participants | 18 Participants | 23 Participants | 19 Participants | 19 Participants | 111 Participants |
| Sex: Female, Male Male | 42 Participants | 25 Participants | 21 Participants | 22 Participants | 19 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 27 / 40 | 33 / 43 | 32 / 42 | 60 / 74 | 24 / 35 | 69 / 106 | 31 / 47 |
| serious Total, serious adverse events | 11 / 40 | 14 / 43 | 12 / 42 | 24 / 74 | 12 / 35 | 46 / 106 | 24 / 47 |
Outcome results
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age | 7.94 hours | Standard Deviation 2.86 |
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age | 24.2 mL/min | Standard Deviation 11.9 |
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | 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 | 36800 hr•ng/mL | Standard Deviation 21800 |
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age | 37200 hr•ng/mL | Standard Deviation 15800 |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age | 30400 hr•ng/mL | Standard Deviation 8290 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age | 9700 hr•ng/mL | Standard Deviation 4200 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age | 4820 hr•ng/mL | Standard Deviation 7240 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age | 45000 hr•ng/mL | Standard Deviation 23800 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age | 21800 hr•ng/mL | Standard Deviation 22200 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age | 19700 hr•ng/mL | Standard Deviation 18500 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age | 1840 hr•ng/mL | Standard Deviation 742 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age | 47400 hr•ng/mL | Standard Deviation 17300 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age | 29200 hr•ng/mL | Standard Deviation 14300 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age | 12000 hr•ng/mL | Standard Deviation 11000 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age | 4260 hr•ng/mL | Standard Deviation 5040 |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age | 33800 hr•ng/mL | Standard Deviation 7180 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age | 12300 hr•ng/mL | Standard Deviation 4660 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age | 3500 hr•ng/mL | Standard Deviation 1430 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age | 46400 hr•ng/mL | Standard Deviation 18600 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age | 15300 hr•ng/mL | Standard Deviation 11100 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age | 16000 hr•ng/mL | Standard Deviation 9680 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age | 2070 hr•ng/mL | Standard Deviation 992 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age | 55300 hr•ng/mL | Standard Deviation 11900 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age | 34300 hr•ng/mL | Standard Deviation 20300 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age | 10700 hr•ng/mL | Standard Deviation 5440 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age | 2860 hr•ng/mL | Standard Deviation 1120 |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | C24hr of Aprepitant in Participants 12 to 17 Years of Age | 735 ng/mL | Standard Deviation 310 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 12 to 17 Years of Age | 142 ng/mL | Standard Deviation 86.4 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 12 to 17 Years of Age | 101 ng/mL | Standard Deviation 247 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | C24hr of Aprepitant in Participants 2 to <6 Years of Age | 1060 ng/mL | Standard Deviation 1020 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 2 to <6 Years of Age | 278 ng/mL | Standard Deviation 398 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 2 to <6 Years of Age | 332 ng/mL | Standard Deviation 430 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 2 to <6 Years of Age | 9.23 ng/mL | Standard Deviation 14.8 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | C24hr of Aprepitant in Participants 6 to <12 Years of Age | 1210 ng/mL | Standard Deviation 1000 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 6 to <12 Years of Age | 589 ng/mL | Standard Deviation 433 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 6 to <12 Years of Age | 219 ng/mL | Standard Deviation 379 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | C24hr of Aprepitant in Participants 6 to <12 Years of Age | 70.4 ng/mL | Standard Deviation 136 |
Primary
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
Population: All participants 12 to 17 years of age that received at least one 5 mg/mL dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
Primary
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
Population: All participants 2 to \<6 years of age that received at least one 5 mg/mL dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | C48hr of Aprepitant in Participants 2 to <6 Years of Age | 232 ng/mL | Standard Deviation 471 |
Primary
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
Population: All participants 6 to \<12 years of age that received at least one 5 mg/mL dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | C48hr of Aprepitant in Participants 6 to <12 Years of Age | 164 ng/mL | Standard Deviation 124 |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | CL/F of Aprepitant in Participants 12 to 17 Years of Age | 76.2 mL/min | Standard Deviation 16.2 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 12 to 17 Years of Age | 91.7 mL/min | Standard Deviation 32.5 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 12 to 17 Years of Age | 105 mL/min | Standard Deviation 29 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | CL/F of Aprepitant in Participants 2 to <6 Years of Age | 31.8 mL/min | Standard Deviation 13.8 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 2 to <6 Years of Age | 66.2 mL/min | Standard Deviation 25.5 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 2 to <6 Years of Age | 29.6 mL/min | Standard Deviation 22.1 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 2 to <6 Years of Age | 48.5 mL/min | Standard Deviation 28.4 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | CL/F of Aprepitant in Participants 6 to <12 Years of Age | 42.1 mL/min | Standard Deviation 12.7 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 6 to <12 Years of Age | 69.2 mL/min | Standard Deviation 66.4 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 6 to <12 Years of Age | 78.8 mL/min | Standard Deviation 39.1 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | CL/F of Aprepitant in Participants 6 to <12 Years of Age | 89.6 mL/min | Standard Deviation 40.9 |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Cmax of Aprepitant in Participants 12 to 17 Years of Age | 3500 ng/mL | Standard Deviation 972 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 12 to 17 Years of Age | 1180 ng/mL | Standard Deviation 408 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 12 to 17 Years of Age | 582 ng/mL | Standard Deviation 437 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Cmax of Aprepitant in Participants 2 to <6 Years of Age | 4270 ng/mL | Standard Deviation 2370 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 2 to <6 Years of Age | 2320 ng/mL | Standard Deviation 1540 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 2 to <6 Years of Age | 2030 ng/mL | Standard Deviation 1780 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 2 to <6 Years of Age | 323 ng/mL | Standard Deviation 103 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Cmax of Aprepitant in Participants 6 to <12 Years of Age | 4400 ng/mL | Standard Deviation 1910 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 6 to <12 Years of Age | 3550 ng/mL | Standard Deviation 2460 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 6 to <12 Years of Age | 1360 ng/mL | Standard Deviation 903 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | Cmax of Aprepitant in Participants 6 to <12 Years of Age | 507 ng/mL | Standard Deviation 443 |
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age | 691 ng/mL | Standard Deviation 852 |
Primary
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
Population: All participants 0 to \<2 years of age that received at least one 5 mg/mL dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age | 352 ng/mL | Standard Deviation 929 |
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age | 3550 ng/mL | Standard Deviation 1500 |
Primary
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
Population: All randomized participants who received at least one dose of study treatment in Cycle 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 | 87.8 Percentage of participants |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 | 83.3 Percentage of participants |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 | 90.7 Percentage of participants |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 | 80.0 Percentage of participants |
| Placebo Control-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 | 77.1 Percentage of participants |
Primary
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)
Population: All randomized participants who received at least one dose of study treatment in Cycles 2-6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6 | 93.6 Percentage of participants |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6 | 75.5 Percentage of participants |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours | 10.5 hours | Standard Deviation 1 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours | 7.92 hours | Standard Deviation 1.38 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours | 8.27 hours | Standard Deviation 1.2 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | t1/2 of Aprepitant in Participants 2 to <6 Years of Age | 9.27 hours | Standard Deviation 4.17 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 2 to <6 Years of Age | 6.55 hours | Standard Deviation 3.62 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 2 to <6 Years of Age | 7.27 hours | Standard Deviation 3.47 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 2 to <6 Years of Age | 6.18 hours | Standard Deviation 3.51 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | t1/2 of Aprepitant in Participants 6 to <12 Years of Age | 9.77 hours | Standard Deviation 2.49 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 6 to <12 Years of Age | 7.69 hours | Standard Deviation 2.09 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 6 to <12 Years of Age | 8.23 hours | Standard Deviation 1.83 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | t1/2 of Aprepitant in Participants 6 to <12 Years of Age | 6.58 hours | Standard Deviation 2.36 |
Primary
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
Population: All participants 0 to \<2 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age | 2.01 hours | Standard Deviation 2.1 |
Primary
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
Population: All participants 12 to 17 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Tmax of Aprepitant in Participants 12 to 17 Years of Age | 0.546 hours | Standard Deviation 0.144 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 12 to 17 Years of Age | 0.722 hours | Standard Deviation 0.608 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 12 to 17 Years of Age | 0.736 hours | Standard Deviation 0.561 |
Primary
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
Population: All participants 2 to \<6 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Tmax of Aprepitant in Participants 2 to <6 Years of Age | 1.90 hours | Standard Deviation 2.16 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 2 to <6 Years of Age | 2.29 hours | Standard Deviation 2.14 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 2 to <6 Years of Age | 1.36 hours | Standard Deviation 0.868 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 2 to <6 Years of Age | 1.34 hours | Standard Deviation 0.771 |
Primary
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
Population: All participants 6 to \<12 years of age that received one dose of study therapy, did not have important deviations from the study protocol, and had data that contributed to the outcome being measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1 | Tmax of Aprepitant in Participants 6 to <12 Years of Age | 2.92 hours | Standard Deviation 5.09 |
| Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 6 to <12 Years of Age | 1.99 hours | Standard Deviation 1.62 |
| Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 6 to <12 Years of Age | 2.14 hours | Standard Deviation 1.96 |
| Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1 | Tmax of Aprepitant in Participants 6 to <12 Years of Age | 1.68 hours | Standard Deviation 2.46 |