Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Aprepitant · 14 trials · 14 indications
Delayed Phase was defined as 25-120 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the delayed phase of Cycle 1.
Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy.
The number of patients who reported No Vomiting in the overall phase in Cycle 1
Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting. Descriptive statistics (means, standard deviations, frequencies, etc.) will be presented for pretreatment patient characteristics. The rate of grade 3 and 4 nausea will be compared to the cut points during interim and final analyses.
Complete control (CC): study days 1-7 (acute and delayed CINV) the proportion of patients achieving complete control (CC); defined as no emetic episode, no need for rescue medication during days 1-7; number of emetic episodes daily; time to first emetic episode; as captured by the MAT (MASCC Antiemesis Tool)/Osoba survey (MASCC refers to Multinational Association for Supportive Care in Cancer™). Severity of nausea and other toxicities measured daily by the NCI Common Toxicity Criteria (version 4.0).
AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using a noncompartmental analysis (NCA). The limit of quantitation (LOQ) value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 125 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 40 mg dose equivalent arm aged birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 12 to 17 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 6 to \<12 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged 2 to \<6 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
AUC0-last was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant AUC0-last assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma AUC0-last was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Cmax was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Cmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Cmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Tmax was analyzed independently for participants in the 10 mg dose equivalent arm aged from birth to \<2 years old due to age- and dose-dependent differences in aprepitant absorption and clearance. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. Plasma for aprepitant Tmax assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Post-operative aprepitant plasma Tmax was evaluated using an NCA. The LOQ value for this analysis was 10 ng/mL.
Plasma for aprepitant AUC0-inf assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. AUC0-inf data were to be log transformed and analyzed via a linear mixed-effects model containing fixed effects for age for each dose level tested.
Plasma for aprepitant CL/F assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. CL/F data were to be log transformed and analyzed via a linear mixed-effects model containing fixed effects for age for each dose level tested.
Plasma for aprepitant t ½ assessment was obtained at 30-60 minutes prior to aprepitant administration, 2-4 hours post aprepitant administration, 5-7 hours post aprepitant administration, and 8-10 hours post aprepitant administration. Because the opportunity to collect specimens for PK analyses in children is limited, a flexible sparse sampling scheme using ranges of collection times was to be utilized which would limit the burden to participants. t ½ data were to be log transformed and analyzed via a linear mixed-effects model containing fixed effects for age for each dose level tested.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, was also an AE. Changes resulting from normal growth and development which did not vary significantly in frequency or severity from expected levels were not to be considered adverse events. Vomiting and retching were not defined as AEs during the period of data collection (24 hours following the end of surgery) unless they met the definition of an SAE. The percentage of participants experiencing ≥1 AE was reported by dose group.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, was also an AE. Changes resulting from normal growth and development which did not vary significantly in frequency or severity from expected levels were not to be considered adverse events. Vomiting and retching were not defined as AEs during the period of data collection (24 hours following the end of surgery) unless they met the definition of an SAE. The percentage of participants discontinuing study due to an AE was reported by dose group.
Blood samples of 0.5 mL were collected from participants for the analysis of AUC0-48 at specified time points: pre-dose, and 1, 2, 3, 4, 8, 12, 24, and 48 hours post aprepitant single dose.
Blood samples were collected from participants for the analysis of Cmax up to 48 hours after dosing.
Blood samples were collected from participants for the analysis of Tmax up to 48 hours after dosing.
Blood samples were collected from participants for the analysis of C24 hr at 24 hours after dosing. N/A indicates that \>50% of measurements were below the lower level of quantitaion (LLOQ).
The mean plasma concentration of aprepitant was evaluated in participants at 48 hours following a single oral dose.
| Arm | Type | Description |
|---|---|---|
| Aprepitant Regimen | EXPERIMENTAL | Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1. |
| Control Regimen | PLACEBO_COMPARATOR | Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1. |
| Aprepitant (MK-0869) | EXPERIMENTAL | - |
| Standard Therapy | PLACEBO_COMPARATOR | - |
| 1 | OTHER | Arm 1: Day 1: aprepitant 125 mg capsule; ondansetron 8 mg capsule prior to chemotherapy and 1 8mg capsule 12 hrs after first dose; dexamethasone 12 mg tablets + 2 dexamethasone Pbo tablets. Day 2: Aprepitant 80 mg capsule; Ondansetron 8 mg capsule every 12 hours Day 3: Aprepitant 80 mg capsule Ondansetron 8 mg capsule every 12 hours. |
| 2 | OTHER | Arm 2: Day 1: Aprepitant 125 mg Pbo capsule; Ondansetron 8 mg capsule prior to chemotherapy and 8 mg capsule 12 hours after first dose; Dexamethasone 20 mg tablets. Day 2: Aprepitant 80 mg Pbo capsule; Ondansetron 8 mg capsule every 12 hours; Day 3: Aprepitant 80 mg Pbo capsule; Ondansetron 8 mg capsule every 12 hours. 3 Day treatment period Optional cycle 2 is being offered to patients. Optional cycle 2 will substitute aprepitant with fosaprepitant dimeglumine 115 mg or Pbo on day 1. All other dosing regimen will remain the same as cycle 1. |
| Part 1: Aprepitant | EXPERIMENTAL | Day 1: aprepitant 125 mg orally (PO), ondansetron 0.15 mg/kg x 3 doses intravenously (IV), dexamethasone 8 mg PO. Day 2: aprepitant 80 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 4 mg PO. Day 3: aprepitant 80 mg PO, dexamethasone 4 mg PO. Day 4: dexamethasone 4 mg PO. For 1 cycle and up to 9 subsequent optional cycles. |
| Part 1: Standard Therapy | ACTIVE_COMPARATOR | Day 1: placebo to aprepitant 125 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 16 mg PO. Day 2: placebo to aprepitant 80 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 8 mg PO. Day 3: placebo for aprepitant 80 mg PO, dexamethasone 8 mg PO. Day 4: dexamethasone 8 mg PO. For 1 cycle; participants may receive open-label aprepitant for up to 9 subsequent optional cycles. |
| Part 2: Aprepitant | ACTIVE_COMPARATOR | Day 1: aprepitant 125 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 8 mg PO. Day 2: aprepitant 80 mg PO, ondansetron 0.15 mg/kg x 3 doses IV, dexamethasone 4 mg PO. Day 3: aprepitant 80 mg PO, dexamethasone 4 mg PO. Day 4: dexamethasone 4 mg PO. For up to 10 cycles. |
| Treatment (antiemetic, chemotherapy, and radiation therapy) | EXPERIMENTAL | CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily on days 1-5 for 5.5 weeks. Patients also receive gemcitabine hydrochloride IV over 30 minutes once weekly and either fluorouracil IV continuously or capecitabine PO twice daily on days 1-5. PROPHYLACTIC THERAPY: Beginning 1 hour before chemoradiotherapy, patients receive aprepitant PO on days 1-3. Treatment repeats every 7 days for 5.5 weeks in the absence of disease progression or unacceptable toxicity. CONSOLIDATION CHEMOTHERAPY: Two to four weeks after completion of chemoradiotherapy and prophylactic therapy, patients without disease progression or a declining performance status receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. |
| aprepitant+ondansetron | ACTIVE_COMPARATOR | On day 1, patients will receive a single oral dose of Aprepitant 125 mg p.o, 1 hour before first dose of the 5-day oral temozolomide regimen. This will be followed by Aprepitant 80 mg p.o. on days 2 -5 (1 hour prior to temozolomide). Additionally, On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide. |
| ondansetron | ACTIVE_COMPARATOR | On days 1-5, patients receive a single dose of Ondansetron 30 minutes before the receiving their prescribed dose of 5-day oral temozolomide. |
| Aprepitant Dose 1: Equivalent to 125 mg in Adults | EXPERIMENTAL | Pediatric participants receive a single dose of apprepitant that is equivalent to 125 mg in adults on Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered intravenously (IV) immediately prior to anesthesia. |
| Aprepitant Dose 2: Equivalent to 40 mg in Adults | EXPERIMENTAL | Pediatric participants receive a single dose of apprepitant that is equivalent to 40 mg in adults on Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered IV immediately prior to anesthesia. |
| Aprepitant Dose 3: Equivalent to 10 mg in Adults | EXPERIMENTAL | Pediatric participants receive a single dose of apprepitant that is equivalent to 10 mg in adults Day 1 between 1 and 3 hours prior to expected induction of anesthesia, plus placebo for odansetron administered IV immediately prior to anesthesia. |
| 3 | EXPERIMENTAL | fosaprepitant 150 mg |
| 4 | EXPERIMENTAL | aprepitant with food |
| Part 1: Oral Aprepitant | EXPERIMENTAL | In Study Part 1, participants aged 6 months to 17 years received a single oral dose of aprepitant on Day 1. |
| Part 2: Oral Aprepitant | EXPERIMENTAL | In Study Part 2, participants aged 6 months to 17 years received a single oral dose of aprepitant on Day 1. |
| Part 2: Intravenous Ondansetron | ACTIVE_COMPARATOR | In Study Part 2, participants aged 6 months to 17 years received a single intravenous dose of ondansetron on Day 1. |
| Name | Type | Description |
|---|---|---|
| Aprepitant 125 mg | DRUG | On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age |
| Aprepitant 80 mg | DRUG | On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age |
| Aprepitant powder for suspension (PFS) | DRUG | On the morning of Day 1: 3.0 mg/kg (up to 125 mg) PO 60 minutes prior to chemotherapy for participants 6 months to \<12 years of age. On the morning of Days 2 and 3: 2.0 mg/kg (up to 80 mg) PO 60 minutes prior to chemotherapy (if applicable) for participants 6 months to \<12 years of age |
| Ondansetron | DRUG | Day 1: Administered according to product label for pediatric usage or local standard of care |
| Placebo for Aprepitant 125 mg | DRUG | On the morning of Day 1: one 125 mg capsule PO 60 minutes prior to chemotherapy for participants 12 to 17 years of age |
| Placebo for Aprepitant 80 mg | DRUG | On the morning of Days 2 and 3: one 80 mg capsule PO for participants 12 to 17 years of age |
| Placebo for Aprepitant PFS | DRUG | On the morning of Day 1: 3.0 mg/kg (up to 125 mg) PO 60 minutes prior to chemotherapy for participants 6 months to \<12 years of age. On the morning of Days 2 and 3: 2.0 mg/kg (up to 80 mg) PO 60 minutes prior to chemotherapy (if applicable) for participants 6 months to \<12 years of age |
| Emetogenic chemotherapy | DRUG | Any moderately or highly emetic chemotherapeutic agent such as cyclophosphamide, doxorubicin, methotrexate, carboplatin, cisplatin, irinotecan, carmustine, ifosfamide, and streptozocin, or chemotherapeutics of a lower emetogenicity that were not previously tolerated. No chemotherapeutic agents were specified by the protocol, and many could potentially have been used." |
| aprepitant | DRUG | Day 1: Oral aprepitant 125 mg prior to administration of cisplatin; Days 2 and 3: Oral aprepitant 80 mg |
| Comparator: Placebo to aprepitant | DRUG | Day 1: Placebo to oral aprepitant 125 mg prior to administration of cisplatin; Days 2 and 3: Placebo to oral aprepitant 80 mg |
| dexamethasone | DRUG | Day 1: Oral dexamethasone 10.5 mg prior to administration of cisplatin; Days 2, 3, and 4: Oral dexamethasone 7.5 mg |
| granisetron | DRUG | Day 1: IV granisetron 3 mg prior to administration of cisplatin |
| Comparator: ondansetron | DRUG | Ondansetron 8 mg capsule Three day treatment period. |
| Comparator: dexamethasone | DRUG | dexamethasone 12 mg tablets; 20 mg tablets Three day treatment period. |
| Comparator: fosaprepitant dimeglumine | DRUG | fosaprepitant dimeglumine 115 mg |
| Comparator; Placebo (unspecified) | DRUG | dexamethasone 12mg Pbo tablets. |
| placebo to aprepitant | DRUG | Matching placebo to aprepitant capsules |
| placebo to dexamethasone | DRUG | Matching placebo to dexamethasone tablets |
| rescue medication | DRUG | Participants are allowed to take rescue medication throughout for nausea or vomiting. At the discretion of the investigator, participants are provided with a prescription for rescue medications. Recommended rescue medications are: 5-HT3 antagonists, phenothiazines, butyrophenones, benzamides, corticosteroids, benzodiazepines, domperidone, H1-receptor antagonist, and piperazine derivatives. |
| Comparator: paroxetine HCL | DRUG | - |
| Comparator: Placebo (Unspecified) | DRUG | - |
| gemcitabine hydrochloride | DRUG | Given IV |
| capecitabine | DRUG | Given PO |
| fluorouracil | DRUG | Given IV |
| radiation therapy | PROCEDURE | Undergo radiation therapy |
| questionnaire administration | OTHER | Ancillary studies |
| quality-of-life assessment | PROCEDURE | Ancillary studies |
| nausea and vomiting therapy | PROCEDURE | Receive aprepitant |
| management of therapy complications | PROCEDURE | Receive aprepitant |
| Placebo to match ondansetron | DRUG | Participants in the aprepitant regimen received normal saline IV (provided by the site) as the placebo for ondansetron on Day 1, immediately prior to induction of anesthesia. |
| aprepitant 165 mg | DRUG | Single dose of aprepitant 165 mg tablet in the fasted state during treatment period 1,2, or 3. |
| Comparator: aprepitant 185 mg | DRUG | Single dose of aprepitant 185 mg tablet in the fasted state during treatment period 1, 2, or 3. |
| Comparator: fosaprepitant 150 mg | DRUG | Single dose of fosaprepitant 150 mg intravenous infusion in the fasted state during treatment period 1,2, or 3. |
| Comparator: aprepitant with food | DRUG | Single dose of aprepitant 165 mg or 185 mg tablet in the fed state during treatment period 4. |
Inclusion Criteria: Cycle 1: * Is 6 months to 17 years of age at time of study entry * Is scheduled to receive chemotherapeutic agent(s) associated with moderate, high risk or very high risk of vomiting for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting...
Aprepitant is a small molecule being developed for vomiting, chemotherapy-induced nausea and vomiting, postoperative nausea and vomiting, extrahepatic bile duct cancer, and major depressive disorder. It is in Phase 3 clinical development and is being studied by Merck & Company, Inc.
Aprepitant is a small molecule that targets the neurokinin-1 receptor, which plays a role in nausea and vomiting. By blocking this receptor, it helps prevent chemotherapy-induced and postoperative nausea and vomiting.
Aprepitant is being developed by Merck & Company, Inc., which is publicly traded under the ticker symbol MRK. The company is conducting clinical trials to evaluate the drug for various gastrointestinal and other conditions.
Aprepitant is in Phase 3 clinical development. It is an investigational drug and has not yet been approved by regulatory authorities. The drug is being studied for multiple indications, including chemotherapy-induced nausea and vomiting and major depressive disorder.
Aprepitant has completed five clinical trials with a total enrollment of 3,290 participants. Notable trials include NCT00819039 in pediatric postoperative nausea and vomiting, NCT01450826 for glioma patients receiving chemotherapy, NCT01534637 for pancreatic cancer, and NCT01732458 for postoperative nausea and vomiting in children.
Aprepitant is the active ingredient in the brand-name drug Emend. In clinical trials, it has been studied under the name MK-0869. Emend is used to prevent nausea and vomiting caused by chemotherapy and surgery.