Chemotherapy-induced Nausea and VomitingPhase 2NCT01697579
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)
A Phase 2 study testing Fosaprepitant, Ondansetron and 5-hydroxytryptamine 3 antagonist in people with Chemotherapy-induced Nausea and Vomiting, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Chemotherapy-induced Nausea and Vomiting
- What is being tested?
- Fosaprepitant, Ondansetron and 5-hydroxytryptamine 3 antagonist
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- No sites listed yet
- Study dates
- 13 Dec 2012to 21 Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
About this study
Official title: A Phase IIb, Partially-Blinded, Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Emetogenic Chemotherapy Sub-title: Open-Label Cohort to Further Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients Birth to <12 Years Old
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.
Read the detailed description
Under Amendment 01, 0517-029 enrolled participants in the following age cohorts: 2-<6, 6-<12 and 12-17 years old. The study was randomized, partially-blinded, with parallel group assignment. Participants were randomized to one of three fosaprepitant doses or the control group. (Amendment 02 and Amendment 03 were country-specific amendments in Brazil that were required as per local regulations with no change in study design.) Under Amendment 04, the 12-17 year-old cohort was closed since that cohort fully enrolled. An additional fosaprepitant dose was added and all participants were allocated to this one treatment group. Amendment 04 was open-label and enrolled participants in the following age cohorts: 0-<2, 2-<6 and 6-<12 years old.
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Being tested
- Fosaprepitant, Fosaprepitant Placebo, Ondansetron, 5-hydroxytryptamine 3 antagonist
- Medical subject headings
- Vomiting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosaprepitantDrug
Also called Fosaprepitant dimeglumine, MK-0517, EMEND® for Injection
Administered intravenously (IV) as a single dose
Fosaprepitant PlaceboDrug
Administered IV as a single dose
OndansetronDrug
Also called Ondansetron hydrochloride, Zofran® Injection
Administered IV according to local labeling and/or local standard of care
5-hydroxytryptamine 3 antagonistDrug
Also called 5-HT3
Administered IV according to local labeling and/or local standard of care
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Fosaprepitant; Drug: 5-hydroxytryptamine 3 antagonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 14 days postdose for each cycle (Cycles 2-6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2012 (estimated)
- Study start13 Dec 2012
- Primary completion21 Nov 2016
- Study completion21 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chemotherapy-induced Nausea and VomitingStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01697579
- Sponsor's protocol ID
- 0517-029
- Other IDs
- 2012-002340-24, MK-0517-029
- Status last verified
- Jun 2019
- First submitted
- 28 Sep 2012
- Last updated
- 25 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
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.
PubMed 30900392
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Partially-Blinded, Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Emetogenic Chemotherapy Sub-title: Open-Label Cohort to Further Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients Birth to <12 Years Old
- ClinicalTrials.gov ID
- NCT01697579
- Acronym / sponsor ID
- 0517-029
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 13 Dec 2012 (actual)
- Primary completion
- 21 Nov 2016 (actual)
- Study completion
- 21 Nov 2016 (actual)
- First posted
- 2 Oct 2012 (estimated)
- Results
- Posted 21 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine the appropriate dosing regimen of fosaprepitant, when administered with ondansetron (with or without dexamethasone), for the prevention of CINV in children from birth to <17 years of age. Fosaprepitant is a prodrug to aprepitant. All participants who completed the randomized Cycle 1 could elect to receive open-label fosaprepitant during optional Cycles 2-6.
Detailed description
Under Amendment 01, 0517-029 enrolled participants in the following age cohorts: 2-<6, 6-<12 and 12-17 years old. The study was randomized, partially-blinded, with parallel group assignment. Participants were randomized to one of three fosaprepitant doses or the control group. (Amendment 02 and Amendment 03 were country-specific amendments in Brazil that were required as per local regulations with no change in study design.) Under Amendment 04, the 12-17 year-old cohort was closed since that cohort fully enrolled. An additional fosaprepitant dose was added and all participants were allocated to this one treatment group. Amendment 04 was open-label and enrolled participants in the following age cohorts: 0-<2, 2-<6 and 6-<12 years old.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Fosaprepitant 5 mg/kg-Cycle 1 | Experimental | Drug: Fosaprepitant, Drug: OndansetronParticipants 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. |
| Fosaprepitant 3 mg/kg-Cycle 1 | Experimental | Drug: Fosaprepitant, Drug: OndansetronParticipants 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. |
| Fosaprepitant 1.2 mg/kg-Cycle 1 | Experimental | Drug: Fosaprepitant, Drug: OndansetronParticipants 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. |
| Fosaprepitant 0.4 mg/kg-Cycle 1 | Experimental | Drug: Fosaprepitant, Drug: OndansetronParticipants 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. |
| Placebo Control-Cycle 1 | Placebo comparator | Drug: Fosaprepitant Placebo, Drug: OndansetronParticipants 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. |
| Fosaprepitant 5 mg/kg-Cycles 2-6 | Experimental | Drug: Fosaprepitant, Drug: 5-hydroxytryptamine 3 antagonistFor 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. |
| Fosaprepitant 3 mg/kg-Cycles 2-6 | Experimental | Drug: Fosaprepitant, Drug: 5-hydroxytryptamine 3 antagonistFor 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. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FosaprepitantAlso: Fosaprepitant dimeglumine, MK-0517, EMEND® for InjectionAdministered intravenously (IV) as a single dose | Drug | 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 PlaceboAdministered IV as a single dose | Drug | Placebo Control-Cycle 1 |
| OndansetronAlso: Ondansetron hydrochloride, Zofran® InjectionAdministered IV according to local labeling and/or local standard of care | Drug | 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 antagonistAlso: 5-HT3Administered IV according to local labeling and/or local standard of care | Drug | Fosaprepitant 3 mg/kg-Cycles 2-6, Fosaprepitant 5 mg/kg-Cycles 2-6 |
Primary outcome
Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Area Under the Concentration-time Curve of Aprepitant From Time 0 to 24 Hours (AUC 0-24hr) in Participants 0 to <2 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Cmax of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Tmax of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
t1/2 of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
C24hr of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
C48hr of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
CL/F of Aprepitant in Participants 2 to <6 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Cmax of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Tmax of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
t1/2 of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
C24hr of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
C48hr of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
CL/F of Aprepitant in Participants 6 to <12 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Cmax of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Tmax of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
C24hr of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Approximately 24 hours (from 23 to 25 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
C48hr of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Approximately 48 hours (from 46 to 50 hours) post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
CL/F of Aprepitant in Participants 12 to 17 Years of Age
Time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1
Time frame: Up to 14 days postdose in Cycle 1
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6
Time frame: Up to 14 days postdose for each cycle (Cycles 2-6)
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30900392Mora 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.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fosaprepitant, Ondansetron and 5-hydroxytryptamine 3 antagonist in people with Chemotherapy-induced Nausea and Vomiting, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age (time frame: Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion). The study lists 34 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01697579, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2019.