Study of the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Children (MK-0517-029)

NCT01697579 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 0517-0292012-002340-24MK-0517-029
• Study Type: interventional
• Target: 240
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chemotherapy-induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (34)

• 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.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Area Under the Concentration-time Curve of Aprepitant From Time 0 to 24 Hours (AUC 0-24hr) in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.

  Approximately 24 hours (from 23 to 25 hours) post-infusion

• Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.

  Approximately 48 hours (from 46 to 50 hours) post-infusion

• Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Cmax of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Tmax of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• t1/2 of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• C24hr of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.

  Approximately 24 hours (from 23 to 25 hours) post-infusion

• C48hr of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.

  Approximately 48 hours (from 46 to 50 hours) post-infusion

• CL/F of Aprepitant in Participants 2 to <6 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Cmax of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Tmax of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• t1/2 of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• C24hr of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.

  Approximately 24 hours (from 23 to 25 hours) post-infusion

• C48hr of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.

  Approximately 48 hours (from 46 to 50 hours) post-infusion

• CL/F of Aprepitant in Participants 6 to <12 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Cmax of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Tmax of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• C24hr of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.

  Approximately 24 hours (from 23 to 25 hours) post-infusion

• C48hr of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.

  Approximately 48 hours (from 46 to 50 hours) post-infusion

• CL/F of Aprepitant in Participants 12 to 17 Years of Age

  Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

  Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

• Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1

  AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.

  Up to 14 days postdose in Cycle 1

• Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6

  AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.

  Up to 14 days postdose for each cycle (Cycles 2-6)

Study Arms (7)

Fosaprepitant 5 mg/kg-Cycle 1

EXPERIMENTAL

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.

Drug: Fosaprepitant; Drug: Ondansetron

Fosaprepitant 3 mg/kg-Cycle 1

EXPERIMENTAL

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 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.

Drug: Fosaprepitant; Drug: Ondansetron

Fosaprepitant 1.2 mg/kg-Cycle 1

EXPERIMENTAL

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 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.

Drug: Fosaprepitant; Drug: Ondansetron

Fosaprepitant 0.4 mg/kg-Cycle 1

EXPERIMENTAL

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 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.

Drug: Fosaprepitant; Drug: Ondansetron

Placebo Control-Cycle 1

PLACEBO COMPARATOR

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.

Drug: Fosaprepitant Placebo; Drug: Ondansetron

Fosaprepitant 5 mg/kg-Cycles 2-6

EXPERIMENTAL

For optional Cycles 2-6, participants from the 5 mg/kg fosaprepitant arm in Cycle 1 were administered fosaprepitant 5 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5- hydroxytryptamine 3 (5-HT3) antagonist with or without dexamethasone. Participants 1 year or less were required to receive ondansetron in all cycles as the 5-HT3 antagonist.

Drug: Fosaprepitant; Drug: 5-hydroxytryptamine 3 antagonist

Fosaprepitant 3 mg/kg-Cycles 2-6

EXPERIMENTAL

For optional Cycles 2-6, participants from Cycle 1 fosaprepitant arms (3, 1.2, or 0.4 mg/kg) or Cycle 1 control arm were administered fosaprepitant 3 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5-HT3 antagonist with or without dexamethasone.

Drug: Fosaprepitant; Drug: 5-hydroxytryptamine 3 antagonist

Interventions

Fosaprepitant DRUG

Administered intravenously (IV) as a single dose

Also known as: Fosaprepitant dimeglumine, MK-0517, EMEND® for Injection

Fosaprepitant 0.4 mg/kg-Cycle 1; Fosaprepitant 1.2 mg/kg-Cycle 1; Fosaprepitant 3 mg/kg-Cycle 1; Fosaprepitant 3 mg/kg-Cycles 2-6; Fosaprepitant 5 mg/kg-Cycle 1; Fosaprepitant 5 mg/kg-Cycles 2-6

Fosaprepitant Placebo DRUG

Administered IV as a single dose

Placebo Control-Cycle 1

Ondansetron DRUG

Administered IV according to local labeling and/or local standard of care

Also known as: Ondansetron hydrochloride, Zofran® Injection

Fosaprepitant 0.4 mg/kg-Cycle 1; Fosaprepitant 1.2 mg/kg-Cycle 1; Fosaprepitant 3 mg/kg-Cycle 1; Fosaprepitant 5 mg/kg-Cycle 1; Placebo Control-Cycle 1

5-hydroxytryptamine 3 antagonist DRUG

Administered IV according to local labeling and/or local standard of care

Also known as: 5-HT3

Fosaprepitant 3 mg/kg-Cycles 2-6; Fosaprepitant 5 mg/kg-Cycles 2-6

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Mora J, Valero M, DiCristina C, Jin M, Chain A, Bickham K. Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients. Pediatr Blood Cancer. 2019 Jun;66(6):e27690. doi: 10.1002/pbc.27690. Epub 2019 Mar 21.

  PMID: 30900392 RESULT

MeSH Terms

Conditions

Vomiting

Interventions

fosaprepitant; Aprepitant; Injections; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2012
• First Posted: October 2, 2012
• Study Start: December 13, 2012
• Primary Completion: November 21, 2016
• Study Completion: November 21, 2016
• Last Updated: June 25, 2019
• Results First Posted: November 21, 2017

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share