Chemotherapy-Induced Nausea and Vomiting
Conditions
Brief summary
This study will determine the appropriate dosing regimen of aprepitant and fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric participants from 0 months to 17 years of age.
Detailed description
Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after intravenous administration; the pharmacological effect of fosaprepitant is attributed to aprepitant. The birth to one year old cohort will be initiated in Parts III and IV upon completion of Part II (Steps A and B) in participants \<6 months of age.
Interventions
DRUGExperimental: aprepitant
aprepitant powder for suspension, 125 mg/sachet, PO
DRUGExperimental: fosaprepitant
fosaprepitant lyophilized powder for suspension, 115 mg/vial or 150 mg/vial, IV
ondansetron solution for infusion, IV, administered per local standard of care
DRUGOndansetron
ondansetron solution for infusion, IV, administered per local standard of care
DRUGDexamethasone
dexamethasone solution for infusion, IV, administered per local standard of care
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Is 0 (at least 37 weeks gestation) to 17 years of age * Is scheduled to receive moderately to highly nausea-inducing chemotherapy or participant did not tolerate a previous chemotherapy regimen that is planned to be repeated * Is expected to receive ondansetron * Female participants who have begun menstruating must have a negative pregnancy test * Weighs ≥3.0 kg if \<6 months of age, ≥6.0 kg if \>6 months of age, and ≥7.5 kg if \> 2 years of age * Has a pre-existing venous catheter
Exclusion criteria
* Uses any illicit drugs or abuses alcohol * Is pregnant or breast feeding * Has a symptomatic central nervous system (CNS) tumor * Has an infection or other uncontrolled disease other than cancer * Has known history of heart QT wave prolongation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Discontinuing Study Drug Due to an AE | Day 1 up to Day 3 | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. The number of participants who discontinued from the study due to an AE are summarized. |
| Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | Up to 24 hours post fosaprepitant/aprepitant dose | AUC is a measure of the amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for pharmacokinetic (PK) assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hours (hr) post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy. |
| Maximum Plasma Concentration (Cmax) for Aprepitant | Up to 72 hours post fosaprepitant/aprepitant dose | Cmax is a measure of the maximum amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy. |
| Time to Cmax (Tmax) for Aprepitant | Up to 72 hours post fosaprepitant/aprepitant dose | Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy. |
| Apparent Terminal Half-life (t1/2) for Aprepitant | Up to 72 hours post fosaprepitant/aprepitant dose | t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy. |
| Cmax for Fosaprepitant | Up to 72 hours post fosaprepitant dose | Cmax is a measure of the maximum amount of fosaprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy. |
| Tmax for Fosaprepitant | Up to 72 hours post fosaprepitant dose | Tmax is a measure of the amount of time after dosing to when the maximum concentration of fosaprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy. |
| Number of Participants Experiencing Adverse Events (AEs) | Up to 14 days after last dose of study drug (Up to 17 days) | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for the occurrence AEs for up to 14 days after last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age | Up to 24 hours post dexamethasone dose | Blood samples for PK assessment were to be collected at the following time points: Parts II and V - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts III and IV - Immediately after infusion of dexamethsone and 0.5, 1.5, 3, 8 and 24 hr post start of chemotherapy. |
Participant flow
Pre-assignment details
Of the 92 unique participants who were enrolled and randomized in Parts I (n=23), II (n=39), III (n=19), IV (n=5) and V (n=6), 91 took part in this study. One participant randomized in Part IIB was discontinued prior to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant Day 1, fosaprepitant IV at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg PO, prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. | 12 |
| Part IB-fosaprepitant 150 mg Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. | 11 |
| Part IIA-aprepitant 80 mg Equiv. Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to \<12 years of age - 47 mg/m\^2; 4 months to \<6 months of age - 2.0 mg/kg; 1 month to \<4 months of age - 1.0 mg/kg; birth to \<1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. | 19 |
| Part IIB-aprepitant 125 mg Equiv. Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to \<12 years of age - 74 mg/m\^2; 6 months to \<2 years of age - 1.3 mg/kg; 4 months to \<6 months of age - 3.0 mg/kg; 1 month to \<4 months of age - 1.5 mg/kg; birth to \<1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. | 20 |
| Part III-ondansetron Ondansetron administered IV per local standard of care on Days 1, 2, and 3 prior to chemotherapy for participants from birth to \<12 years of age. The use of IV dexamethasone is optional with the exception of the birth to one year old cohort. | 19 |
| Part IV-aprepitant Regimen Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to \<12 years of age - 3.0 mg/kg; 1 month to \<4 months of age - 1.5 mg/kg; Birth to \<1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to \<12 years of age - 2.0 mg/kg; 1 month to \<4 months of age - 1.0 mg/kg; Birth to \<1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to one year old cohort. | 5 |
| Part V-fosaprepitant Regimen Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to \<12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. | 6 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part I | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part II | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part II | Not Treated | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part II | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part IV | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part V | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part V-fosaprepitant Regimen | Part IV-aprepitant Regimen | Part III-ondansetron | Part IIB-aprepitant 125 mg Equiv. | Part IIA-aprepitant 80 mg Equiv. | Part IB-fosaprepitant 150 mg | Part IA-fosaprepitant 115 mg/Aprepitant |
|---|---|---|---|---|---|---|---|---|
| Age, Customized 12 years to 17 years | 23 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 12 Participants |
| Age, Customized 2 years to <6 years | 25 Participants | 3 Participants | 0 Participants | 6 Participants | 8 Participants | 8 Participants | 0 Participants | 0 Participants |
| Age, Customized 6 months to <2 years | 19 Participants | 1 Participants | 1 Participants | 6 Participants | 6 Participants | 5 Participants | 0 Participants | 0 Participants |
| Age, Customized 6 years to <12 years | 25 Participants | 2 Participants | 4 Participants | 7 Participants | 6 Participants | 6 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 62 Participants | 6 Participants | 3 Participants | 13 Participants | 14 Participants | 12 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Male | 30 Participants | 0 Participants | 2 Participants | 6 Participants | 6 Participants | 7 Participants | 4 Participants | 5 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 | 11 / 12 | 5 / 11 | 18 / 19 | 15 / 19 | 15 / 19 | 13 / 20 | 16 / 23 |
| serious Total, serious adverse events | 4 / 12 | 1 / 11 | 7 / 19 | 4 / 19 | 5 / 19 | 2 / 20 | 9 / 23 |
Outcome results
Primary
Apparent Terminal Half-life (t1/2) for Aprepitant
t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Time frame: Up to 72 hours post fosaprepitant/aprepitant dose
Population: The population consisted of all participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for this PK parameter. No PK assessements were performed on the Part III-ondansetron group; this group received no aprepitant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6) | NA hr | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Apparent Terminal Half-life (t1/2) for Aprepitant | 2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7) | NA hr | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8) | NA hr | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Apparent Terminal Half-life (t1/2) for Aprepitant | 12 years to 17 years (n=6 11, 0, 0, 0, 0, 0) | 11.0 hr | Standard Deviation 4.42 |
| Part IB-fosaprepitant 150 mg | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Apparent Terminal Half-life (t1/2) for Aprepitant | 2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Apparent Terminal Half-life (t1/2) for Aprepitant | 12 years to 17 years (n=6 11, 0, 0, 0, 0, 0) | 22.2 hr | Standard Deviation 19.8 |
| Part IIA-aprepitant 80 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 12 years to 17 years (n=6 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part IIA-aprepitant 80 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8) | 9.17 hr | Standard Deviation 4 |
| Part IIA-aprepitant 80 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7) | 8.27 hr | Standard Deviation 2.67 |
| Part IIA-aprepitant 80 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6) | 7.28 hr | Standard Deviation 1.47 |
| Part IIB-aprepitant 125 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6) | 8.09 hr | Standard Deviation 2.54 |
| Part IIB-aprepitant 125 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 12 years to 17 years (n=6 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part IIB-aprepitant 125 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7) | 6.06 hr | Standard Deviation 3.03 |
| Part IIB-aprepitant 125 mg Equiv. | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8) | 6.89 hr | Standard Deviation 1.35 |
| Part IV-aprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8) | 10.8 hr | Standard Deviation 4.27 |
| Part IV-aprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 12 years to 17 years (n=6 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part IV-aprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7) | 9.21 hr | Standard Deviation 5.57 |
| Part IV-aprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6) | 6.18 hr | Standard Deviation 4.12 |
| Part V-fosaprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7) | 6.44 hr | Standard Deviation 2.35 |
| Part V-fosaprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8) | 8.76 hr | Standard Deviation 3.34 |
| Part V-fosaprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 12 years to 17 years (n=6 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part V-fosaprepitant Regimen | Apparent Terminal Half-life (t1/2) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6) | 7.71 hr | Standard Deviation 3.1 |
Primary
Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant
AUC is a measure of the amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for pharmacokinetic (PK) assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hours (hr) post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy.
Time frame: Up to 24 hours post fosaprepitant/aprepitant dose
Population: The population consisted of all participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for this PK parameter. No PK assessements were performed on the Part III-ondansetron group; this group received no aprepitant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6) | NA hr*ng/mL | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | NA hr*ng/mL | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8) | NA hr*ng/mL | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0) | 19500 hr*ng/mL | Standard Deviation 8010 |
| Part IB-fosaprepitant 150 mg | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8) | NA hr*ng/mL | — |
| Part IB-fosaprepitant 150 mg | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | NA hr*ng/mL | — |
| Part IB-fosaprepitant 150 mg | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6) | NA hr*ng/mL | — |
| Part IB-fosaprepitant 150 mg | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0) | 30800 hr*ng/mL | Standard Deviation 7020 |
| Part IIA-aprepitant 80 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0) | NA hr*ng/mL | — |
| Part IIA-aprepitant 80 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8) | 16000 hr*ng/mL | Standard Deviation 4810 |
| Part IIA-aprepitant 80 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 16400 hr*ng/mL | Standard Deviation 8080 |
| Part IIA-aprepitant 80 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6) | 20000 hr*ng/mL | Standard Deviation 7890 |
| Part IIB-aprepitant 125 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6) | 6310 hr*ng/mL | Standard Deviation 2040 |
| Part IIB-aprepitant 125 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0) | NA hr*ng/mL | — |
| Part IIB-aprepitant 125 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 23000 hr*ng/mL | Standard Deviation 8390 |
| Part IIB-aprepitant 125 mg Equiv. | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8) | 22000 hr*ng/mL | Standard Deviation 9440 |
| Part IV-aprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8) | 24400 hr*ng/mL | Standard Deviation 15800 |
| Part IV-aprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0) | NA hr*ng/mL | — |
| Part IV-aprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 17300 hr*ng/mL | Standard Deviation 5060 |
| Part IV-aprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6) | 21100 hr*ng/mL | Standard Deviation 11800 |
| Part V-fosaprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 18300 hr*ng/mL | Standard Deviation 11100 |
| Part V-fosaprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8) | 19500 hr*ng/mL | Standard Deviation 6720 |
| Part V-fosaprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0) | NA hr*ng/mL | — |
| Part V-fosaprepitant Regimen | Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6) | 11700 hr*ng/mL | Standard Deviation 6980 |
Primary
Cmax for Fosaprepitant
Cmax is a measure of the maximum amount of fosaprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Time frame: Up to 72 hours post fosaprepitant dose
Population: The population consisted of all participants who received at least one dose of fosaprepitant \& were evaluable for this PK parameter. No PK analyses were performed on the Part 1A-fosaprepitant 115 mg/aprepitant group; blood samples from this group were not handled correctly. Part IIA, Part IIB, Part III \& Part IV groups received no fosaprepitant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part IB-fosaprepitant 150 mg | Cmax for Fosaprepitant | 6 months to <2 years (n=0, 0, 0, 0, 0, 0, 7) | NA ng/mL | — |
| Part IB-fosaprepitant 150 mg | Cmax for Fosaprepitant | 2 years to <6 years (n=0, 0, 0, 0, 0, 0, 8) | NA ng/mL | — |
| Part IB-fosaprepitant 150 mg | Cmax for Fosaprepitant | 6 years to <12 years (n=0, 0, 0, 0, 0, 0, 8) | NA ng/mL | — |
| Part IB-fosaprepitant 150 mg | Cmax for Fosaprepitant | 12 years to 17 years (n=0, 11, 0, 0, 0, 0, 0) | 1310 ng/mL | Standard Deviation 964 |
| Part V-fosaprepitant Regimen | Cmax for Fosaprepitant | 12 years to 17 years (n=0, 11, 0, 0, 0, 0, 0) | NA ng/mL | — |
| Part V-fosaprepitant Regimen | Cmax for Fosaprepitant | 6 months to <2 years (n=0, 0, 0, 0, 0, 0, 7) | 2756 ng/mL | Standard Deviation 3364 |
| Part V-fosaprepitant Regimen | Cmax for Fosaprepitant | 6 years to <12 years (n=0, 0, 0, 0, 0, 0, 8) | 1654 ng/mL | Standard Deviation 1995 |
| Part V-fosaprepitant Regimen | Cmax for Fosaprepitant | 2 years to <6 years (n=0, 0, 0, 0, 0, 0, 8) | 3034 ng/mL | Standard Deviation 1718 |
Primary
Maximum Plasma Concentration (Cmax) for Aprepitant
Cmax is a measure of the maximum amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Time frame: Up to 72 hours post fosaprepitant/aprepitant dose
Population: The population consisted of all participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for this PK parameter. No PK assessements were performed on the Part III-ondansetron group; this group received no aprepitant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | NA ng/mL | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Maximum Plasma Concentration (Cmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | NA ng/mL | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | NA ng/mL | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Maximum Plasma Concentration (Cmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | 3240 ng/mL | Standard Deviation 1280 |
| Part IB-fosaprepitant 150 mg | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | NA ng/mL | — |
| Part IB-fosaprepitant 150 mg | Maximum Plasma Concentration (Cmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | NA ng/mL | — |
| Part IB-fosaprepitant 150 mg | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | NA ng/mL | — |
| Part IB-fosaprepitant 150 mg | Maximum Plasma Concentration (Cmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | 5870 ng/mL | Standard Deviation 2770 |
| Part IIA-aprepitant 80 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA ng/mL | — |
| Part IIA-aprepitant 80 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 1300 ng/mL | Standard Deviation 275 |
| Part IIA-aprepitant 80 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 1300 ng/mL | Standard Deviation 609 |
| Part IIA-aprepitant 80 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 1930 ng/mL | Standard Deviation 1000 |
| Part IIB-aprepitant 125 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 659 ng/mL | Standard Deviation 107 |
| Part IIB-aprepitant 125 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA ng/mL | — |
| Part IIB-aprepitant 125 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 2100 ng/mL | Standard Deviation 1170 |
| Part IIB-aprepitant 125 mg Equiv. | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 1930 ng/mL | Standard Deviation 873 |
| Part IV-aprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 1800 ng/mL | Standard Deviation 1610 |
| Part IV-aprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA ng/mL | — |
| Part IV-aprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 1840 ng/mL | Standard Deviation 933 |
| Part IV-aprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 1810 ng/mL | Standard Deviation 925 |
| Part V-fosaprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 2430 ng/mL | Standard Deviation 1100 |
| Part V-fosaprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 2850 ng/mL | Standard Deviation 641 |
| Part V-fosaprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA ng/mL | — |
| Part V-fosaprepitant Regimen | Maximum Plasma Concentration (Cmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 1700 ng/mL | Standard Deviation 636 |
Primary
Number of Participants Discontinuing Study Drug Due to an AE
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. The number of participants who discontinued from the study due to an AE are summarized.
Time frame: Day 1 up to Day 3
Population: The ASaT population consisted of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| Part IB-fosaprepitant 150 mg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| Part IIA-aprepitant 80 mg Equiv. | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| Part IIB-aprepitant 125 mg Equiv. | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| Part III-ondansetron | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| Part IV-aprepitant Regimen | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| Part V-fosaprepitant Regimen | Number of Participants Discontinuing Study Drug Due to an AE | 1 Participants |
Primary
Number of Participants Experiencing Adverse Events (AEs)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for the occurrence AEs for up to 14 days after last dose of study drug.
Time frame: Up to 14 days after last dose of study drug (Up to 17 days)
Population: The All Subjects as Treated (ASaT) population consisted of all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant | Number of Participants Experiencing Adverse Events (AEs) | 11 Participants |
| Part IB-fosaprepitant 150 mg | Number of Participants Experiencing Adverse Events (AEs) | 6 Participants |
| Part IIA-aprepitant 80 mg Equiv. | Number of Participants Experiencing Adverse Events (AEs) | 18 Participants |
| Part IIB-aprepitant 125 mg Equiv. | Number of Participants Experiencing Adverse Events (AEs) | 16 Participants |
| Part III-ondansetron | Number of Participants Experiencing Adverse Events (AEs) | 15 Participants |
| Part IV-aprepitant Regimen | Number of Participants Experiencing Adverse Events (AEs) | 13 Participants |
| Part V-fosaprepitant Regimen | Number of Participants Experiencing Adverse Events (AEs) | 17 Participants |
Primary
Time to Cmax (Tmax) for Aprepitant
Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Time frame: Up to 72 hours post fosaprepitant/aprepitant dose
Population: The population consisted of all participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for this PK parameter. No PK assessements were performed on the Part III-ondansetron group; this group received no aprepitant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part IA-fosaprepitant 115 mg/Aprepitant | Time to Cmax (Tmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | NA hr | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Time to Cmax (Tmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | NA hr | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Time to Cmax (Tmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | NA hr | — |
| Part IA-fosaprepitant 115 mg/Aprepitant | Time to Cmax (Tmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | 0.41 hr | Standard Deviation 0.27 |
| Part IB-fosaprepitant 150 mg | Time to Cmax (Tmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Time to Cmax (Tmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Time to Cmax (Tmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Time to Cmax (Tmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | 0.64 hr | Standard Deviation 0.3 |
| Part IIA-aprepitant 80 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 3.78 hr | Standard Deviation 1.92 |
| Part IIA-aprepitant 80 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 2.33 hr | Standard Deviation 1.16 |
| Part IIA-aprepitant 80 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 5.17 hr | Standard Deviation 1.83 |
| Part IIA-aprepitant 80 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part IIB-aprepitant 125 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part IIB-aprepitant 125 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 3.45 hr | Standard Deviation 2.89 |
| Part IIB-aprepitant 125 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 5.28 hr | Standard Deviation 1.97 |
| Part IIB-aprepitant 125 mg Equiv. | Time to Cmax (Tmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 3.08 hr | Standard Deviation 0.95 |
| Part IV-aprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 6.42 hr | Standard Deviation 7.84 |
| Part IV-aprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 7.34 hr | Standard Deviation 8.28 |
| Part IV-aprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part IV-aprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 4.92 hr | Standard Deviation 2.2 |
| Part V-fosaprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7) | 1.41 hr | Standard Deviation 0.83 |
| Part V-fosaprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7) | 1.13 hr | Standard Deviation 0.17 |
| Part V-fosaprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part V-fosaprepitant Regimen | Time to Cmax (Tmax) for Aprepitant | 6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8) | 1.07 hr | Standard Deviation 0.11 |
Primary
Tmax for Fosaprepitant
Tmax is a measure of the amount of time after dosing to when the maximum concentration of fosaprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
Time frame: Up to 72 hours post fosaprepitant dose
Population: The population consisted of all participants who received at least one dose of fosaprepitant \& were evaluable for this PK parameter. No PK analyses were performed on the Part 1A-fosaprepitant 115 mg/aprepitant group; blood samples from this group were not handled correctly. Part IIA, Part IIB, Part III \& Part IV groups received no fosaprepitant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part IB-fosaprepitant 150 mg | Tmax for Fosaprepitant | 6 months to <2 years (n=0, 0, 0, 0, 0, 0, 7) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Tmax for Fosaprepitant | 2 years to <6 years (n=0, 0, 0, 0, 0, 0, 7) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Tmax for Fosaprepitant | 6 years to <12 years (n=0, 0, 0, 0, 0, 0, 8) | NA hr | — |
| Part IB-fosaprepitant 150 mg | Tmax for Fosaprepitant | 12 years to 17 years (n=0, 11, 0, 0, 0, 0, 0) | 0.614 hr | Standard Deviation 0.251 |
| Part V-fosaprepitant Regimen | Tmax for Fosaprepitant | 12 years to 17 years (n=0, 11, 0, 0, 0, 0, 0) | NA hr | — |
| Part V-fosaprepitant Regimen | Tmax for Fosaprepitant | 6 months to <2 years (n=0, 0, 0, 0, 0, 0, 7) | 1.13 hr | Standard Deviation 0.175 |
| Part V-fosaprepitant Regimen | Tmax for Fosaprepitant | 6 years to <12 years (n=0, 0, 0, 0, 0, 0, 8) | 1.04 hr | Standard Deviation 0.088 |
| Part V-fosaprepitant Regimen | Tmax for Fosaprepitant | 2 years to <6 years (n=0, 0, 0, 0, 0, 0, 7) | 1.05 hr | Standard Deviation 0.089 |
Secondary
Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age
Blood samples for PK assessment were to be collected at the following time points: Parts II and V - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts III and IV - Immediately after infusion of dexamethsone and 0.5, 1.5, 3, 8 and 24 hr post start of chemotherapy.
Time frame: Up to 24 hours post dexamethasone dose
Population: This population was to consist of all participants from birth to 1 year of age who received at least one dose of dexamethasone and were evaluable for this PK parameter. These analyses were not conducted; enrollment of this cohort was not opened as enrollment of participants from birth to \<6 months of age into Part II was unsuccessful.