Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)

• ClinicalTrials.gov Identifier: NCT01594749
• Recruitment Status: Completed
• First Posted: May 9, 2012
• Results First Posted: September 25, 2015
• Last Update Posted: September 4, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Chemotherapy-Induced Nausea and Vomiting (CINV)
• Interventions: Drug: Fosaprepitant dimeglumine; Drug: Fosaprepitant Placebo; Drug: Dexamethasone; Drug: Ondansetron; Drug: Dexamethasone Placebo; Drug: Ondansetron Placebo; Drug: Rescue Therapy
• Enrollment: 1015

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 14 participants did not receive any study drug: 4 in the Fosaprepitant Regimen and 10 in the Control Regimen. One participant who was randomized to the Control Regimen received the Fosaprepitant Regimen.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description	On Day 1, participants received fosaprepitant, 150 mg intravenous (IV) infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, orally (PO) ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-hydroxytryptamine 3 (5-HT3) antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Period Title: Overall Study
Started	507	508
Treated	503	498
Completed	485	490
Not Completed	22	18
Reason Not Completed
Adverse Event	2	1
Withdrawal by Subject	2	2
Protocol Violation	2	0
Physician Decision	1	1
Non-compliance with Protocol	0	1
Lost to Follow-up	1	0
Death	9	3
Not Treated	4	10
Lost Source Documentation	1	0

Baseline Characteristics

Arm/Group Title		Fosaprepitant Regimen	Control Regimen	Total
Arm/Group Description		On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	Total of all reporting groups
Overall Number of Baseline Participants		502	498	1000
Baseline Analysis Population Description		The Baseline analysis population is consistent with the Intent-to-Treat (ITT) population, i.e., all randomized participants who received ≥1 dose of study drug within the assigned treatment regimen. Note: One participant with missing source documentation in the Fosaprepitant Regimen was excluded from the ITT population.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	502 participants	498 participants	1000 participants
		60.0 (11.8)	59.1 (12.3)	59.6 (12.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	502 participants	498 participants	1000 participants
	Female	298 59.4%	293 58.8%	591 59.1%
	Male	204 40.6%	205 41.2%	409 40.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC)
Description	A Complete Response was defined as no vomiting and no use of rescue medication.
Time Frame	25 to 120 hours after initiation of MEC

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants who received ≥1 dose of study drug within the assigned treatment regimen. One participant in the Fosaprepitant Regimen was excluded from the ITT population due to missing source documentation. One participant in the Control Regimen was treated with fosaprepitant in error.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description:	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Overall Number of Participants Analyzed	502	498
Measure Type: Number; Unit of Measure: Percentage of Participants
	78.9	68.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosaprepitant Regimen, Control Regimen
	Comments	Percentage difference in Fosaprepitant Regimen vs. Control Regimen
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value based on Cochran-Mantel-Haenszel (CMH) method with stratification of gender
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants With Infusion-site Thrombophlebitis
Description	The percentages of participants with infusion-site thrombophlebitis are presented. Thrombophlebitis was defined as a condition affecting a superficial vein used for an IV infusion, associated with red color, hardness upon palpation, and the presence of a tender cord and possible fever.
Time Frame	Day 1 through Day 17, inclusive

Outcome Measure Data

Analysis Population Description

The Safety population consisted of all randomized participants who received study drug as treated.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description:	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Overall Number of Participants Analyzed	504	497
Measure Type: Number; Unit of Measure: Percentage of Participants
	0.6	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosaprepitant Regimen, Control Regimen
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.085
	Comments	P-value based on Miettinen & Nurminen method
	Method	Miettinen & Nurminen method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in percentage vs. Control
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.2 to 1.7
	Estimation Comments	[Not Specified]

3. Primary Outcome

Title	Percentage of Participants With Severe Infusion-site Reactions
Description	The percentages of participants with severe infusion-site reactions, including severe site pain, or severe site redness (erythema) or severe site hardness (induration) are presented.
Time Frame	Day 1 through Day 17, inclusive

Outcome Measure Data

Analysis Population Description

The Safety population consisted of all randomized participants who received study drug as treated.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description:	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Overall Number of Participants Analyzed	504	497
Measure Type: Number; Unit of Measure: Percentage of Participants
	0.0	0.0

4. Secondary Outcome

Title	Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC
Description	A Complete Response was defined as no vomiting and no use of rescue medication.
Time Frame	0 to 120 hours after initiation of MEC

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants who received ≥1 dose of study drug within the assigned treatment regimen. One participant in the Fosaprepitant Regimen was excluded from the ITT population due to missing source documentation. One participant in the Control Regimen was treated with fosaprepitant in error.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description:	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Overall Number of Participants Analyzed	502	498
Measure Type: Number; Unit of Measure: Percentage of Participants
	77.1	66.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosaprepitant Regimen, Control Regimen
	Comments	Percentage difference in Fosaprepitant Regimen vs. Control Regimen
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value based on CMH method with stratification of gender
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC
Description	A Complete Response was defined as no vomiting and no use of rescue medication.
Time Frame	0 to 24 hours after initiation of MEC

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants who received ≥1 dose of study drug within the assigned treatment regimen. One participant in the Fosaprepitant Regimen was excluded from the ITT population due to missing source documentation. One participant in the Control Regimen was treated with fosaprepitant in error.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description:	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Overall Number of Participants Analyzed	502	498
Measure Type: Number; Unit of Measure: Percentage of Participants
	93.2	91.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosaprepitant Regimen, Control Regimen
	Comments	Percentage difference in Fosaprepitant Regimen vs. Control Regimen
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.184
	Comments	P-value based on CMH method with stratification of gender
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC
Description	No Vomiting was defined as no emetic (vomiting) episodes, including no vomiting and no retching or dry heaves (attempts to vomit that are not productive of stomach contents), regardless of use of rescue medication.
Time Frame	0 to 120 hours after initiation of MEC

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all randomized participants who received ≥1 dose of study drug within the assigned treatment regimen. One participant in the Fosaprepitant Regimen was excluded from the ITT population due to missing source documentation. One participant in the Control Regimen was treated with fosaprepitant in error.

Arm/Group Title	Fosaprepitant Regimen	Control Regimen
Arm/Group Description:	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.	On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Overall Number of Participants Analyzed	502	498
Measure Type: Number; Unit of Measure: Percentage of participants
	82.7	72.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fosaprepitant Regimen, Control Regimen
	Comments	Percentage difference in Fosaprepitant Regimen vs. Control Regimen
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-value based on CMH method with stratification of gender
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Adverse Events

Time Frame	Day 1 up to Day 17, inclusive (Up to 2 weeks after last dose of study drug)
Adverse Event Reporting Description	The Safety population consisted of all participants who received study drug. Participants are included in the treatment group based on the study drug they actually received.
Arm/Group Title	Fosaprepitant Regimen		Control Regimen
Arm/Group Description	On Day 1, participants received fosaprepitant, 150 mg IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.		On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
All-Cause Mortality
	Fosaprepitant Regimen		Control Regimen
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Fosaprepitant Regimen		Control Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/504 (7.74%)		35/497 (7.04%)
Blood and lymphatic system disorders
Abdominal lymphadenopathy † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Anaemia † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Febrile neutropenia † 1	8/504 (1.59%)	8	5/497 (1.01%)	5
Leukocytosis † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Leukopenia † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Neutropenia † 1	3/504 (0.60%)	3	4/497 (0.80%)	4
Cardiac disorders
Angina pectoris † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Atrial fibrillation † 1	1/504 (0.20%)	1	1/497 (0.20%)	2
Cardiac arrest † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Cardiac disorder † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Supraventricular tachycardia † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Gastrointestinal disorders
Abdominal pain † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Colitis † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Constipation † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Diarrhoea † 1	1/504 (0.20%)	1	1/497 (0.20%)	1
Gastrointestinal disorder † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Gastrooesophageal reflux disease † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Nausea † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Neutropenic colitis † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Pancreatitis † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Vomiting † 1	1/504 (0.20%)	1	1/497 (0.20%)	1
General disorders
Asthenia † 1	1/504 (0.20%)	1	2/497 (0.40%)	2
Death † 1	2/504 (0.40%)	2	0/497 (0.00%)	0
Disease progression † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Fatigue † 1	1/504 (0.20%)	1	1/497 (0.20%)	1
Pyrexia † 1	2/504 (0.40%)	2	1/497 (0.20%)	1
Hepatobiliary disorders
Hepatorenal failure † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Immune system disorders
Drug hypersensitivity † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Hypersensitivity † 1	1/504 (0.20%)	1	1/497 (0.20%)	1
Infections and infestations
Diverticulitis † 1	0/504 (0.00%)	0	2/497 (0.40%)	2
Influenza † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Lower respiratory tract infection † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Oral candidiasis † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Pneumonia † 1	1/504 (0.20%)	1	3/497 (0.60%)	3
Respiratory tract infection † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Sepsis † 1	2/504 (0.40%)	2	0/497 (0.00%)	0
Injury, poisoning and procedural complications
Fracture † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Toxicity to various agents † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Investigations
Blood glucose increased † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Haemoglobin decreased † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Dehydration † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Musculoskeletal and connective tissue disorders
Back pain † 1	1/504 (0.20%)	1	2/497 (0.40%)	2
Myalgia † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Metastases to bone † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Non-small cell lung cancer † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Nervous system disorders
Cerebral infarction † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Epilepsy † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Syncope † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Transient ischaemic attack † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Psychiatric disorders
Mental status changes † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Haemoptysis † 1	1/504 (0.20%)	1	1/497 (0.20%)	1
Pleural effusion † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
Pneumothorax † 1	0/504 (0.00%)	0	1/497 (0.20%)	1
Pulmonary embolism † 1	2/504 (0.40%)	2	0/497 (0.00%)	0
Vascular disorders
Thrombosis † 1	1/504 (0.20%)	1	0/497 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Fosaprepitant Regimen		Control Regimen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	190/504 (37.70%)		193/497 (38.83%)
Blood and lymphatic system disorders
Neutropenia † 1	38/504 (7.54%)	38	33/497 (6.64%)	33
Gastrointestinal disorders
Constipation † 1	47/504 (9.33%)	48	51/497 (10.26%)	53
Diarrhoea † 1	63/504 (12.50%)	66	55/497 (11.07%)	57
General disorders
Fatigue † 1	75/504 (14.88%)	78	64/497 (12.88%)	64
Metabolism and nutrition disorders
Decreased appetite † 1	26/504 (5.16%)	27	32/497 (6.44%)	32
Nervous system disorders
Headache † 1	30/504 (5.95%)	32	35/497 (7.04%)	37
Skin and subcutaneous tissue disorders
Alopecia † 1	11/504 (2.18%)	11	26/497 (5.23%)	26
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Vallejos W, Liang LW, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: results of a randomized, double-blind phase III trial. Ann Oncol. 2016 Jan;27(1):172-8. doi: 10.1093/annonc/mdv482. Epub 2015 Oct 8.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Weinstein C, Jordan K, Green S, Khanani S, Beckford-Brathwaite E, Vallejos W, Pong A, Noga SJ, Rapoport BL. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy regimens: a subgroup analysis from a randomized clinical trial of response in subjects by cancer type. BMC Cancer. 2020 Sep 25;20(1):918. doi: 10.1186/s12885-020-07259-5.

Weinstein C, Jordan K, Green SA, Camacho E, Khanani S, Beckford-Brathwaite E, Pong A, Noga SJ, Rapoport BL. Evaluation of factors contributing to the response to fosaprepitant in a heterogeneous, moderately emetogenic chemotherapy population: an exploratory analysis of a randomized phase III trial. Support Care Cancer. 2018 Nov;26(11):3773-3780. doi: 10.1007/s00520-018-4242-x. Epub 2018 May 28.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01594749
• Other Study ID Numbers: 0517-031
• First Submitted: April 24, 2012
• First Posted: May 9, 2012
• Results First Submitted: August 26, 2015
• Results First Posted: September 25, 2015
• Last Update Posted: September 4, 2018