Symptoms and General Pathology

All Conditions

Nausea

Vomiting

Signs and Symptoms, Digestive

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antirheumatic Agents

Emetics

Anti-Infective Agents

Cardiotonic Agents

Ondansetron

Granisetron

Dexamethasone

Cyclophosphamide

Fosaprepitant

Aprepitant

Dexamethasone acetate

BB 1101

Metoclopramide

Serotonin

Tropisetron

Dolasetron

Alizapride

Dexamethasone 21-phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Serotonin 5-HT3 Receptor Antagonists

Neurotransmitter Agents

Neurokinin-1 Receptor Antagonists

Substance P

Neurokinin A

Dopamine

Dopamine Antagonists

Dopamine Agents

Participants receive one aprepitant 125 mg capsule by mouth (PO) once daily (QD) on Day 1 and one aprepitant 80 mg capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg intravenously (IV) QD and dexamethasone 12 mg PO on Day 1 and placebo for ondansetron 8 mg PO twice daily (BID) on Days 2 and 3.

Participants receive one placebo capsule PO QD on Day 1 and one placebo capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg IV QD and dexamethasone 20 mg PO on Day 1 and ondansetron 8 mg PO BID on Days 2 and 3.

Aprepitant (125 mg PO, QD) on Day 1, Aprepitant (80 mg PO, QD) on Days 2 and 3

Aprepitant Placebo (PO, QD) on Days 1, 2, and 3

Aprepitant Placebo

Ondansetron (16 mg, IV, QD) on Day 1 and/or ondansetron (8 mg PO BID) on Days 2 and 3

Dexamethasone (20 mg or 12 mg, PO) on Day 1

Ondansetron Placebo (PO, BID) on Days 2 and 3

Ondansetron Placebo

Use of a rescue therapy for nausea and vomiting is permitted throughout the study. Permitted rescue therapies include a drug from among the following classes: 5-hydroxytryptamine (5-HT3) antagonists (granisetron, dolasetron, tropisetron or ondansetron), benzodiazepines, or benzamides (e.g., metoclopramide or alizapride).

Rescue Therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).

Medical Director

This is an efficacy and safety study to compare aprepitant with ondansetron for the prevention of nausea and vomiting in the first cycle of moderately emetogenic chemotherapy (MEC) in participants with solid tumors. MECs include a number of commonly used cancer chemotherapeutic drugs including: oxaliplatin-based, irinotecan-based, and carboplatin-based regimens.

The primary hypothesis of this study is that the Aprepitant Regimen is superior to the Control (ondansetron) Regimen with respect to the percentage of participants with No Vomiting Overall (in the 120 hours following initiation of MEC) in participants with solid tumors.

A Korean Study of Efficacy and Safety of Aprepitant-based Triple Regimen for the Prevention of Chemotherapy-Induced Nausea and Vomiting in the First Cycle of Moderately Emetogenic Chemotherapy (Non-doxorubicin Hydrochloride [Adriamycin] and Cyclophosphamide Regimens) (MK-0869-225) (KMEC)

A Korean Multicenter, Randomized, Double-Blind, Clinical Trial to Evaluate the Efficacy and Tolerability of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in the First Cycle of Moderately Emetogenic Chemotherapies (MEC, Non-AC Regimes) With Broad Range of Tumor Types (KMEC Study)

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

A vomiting episode was defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). No vomiting during the Overall Stage was defined as no episodes of emesis during the 120 hours (Days 1-5) after initiation of moderately emetogenic chemotherapy (MEC).

A Complete Response was defined as no vomiting or dry heaves and no use of a rescue therapy. Overall Stage=0 to 120 hours after initiation of MEC. Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.

The number of emetic events that occurred during the Overall Stage (0 to 120 hours after initiation of MEC) are presented.

Nausea was to be assessed using a 100-mm horizontal visual analogue scale (VAS) located in the participant diary labeled: "How much nausea have you had over the last 24 hours?" The left end of the scale (0 mm) was labeled "no nausea," and the right end of the scale (100 mm) is labeled "nausea as bad as it could be." In this study, No Significant Nausea was defined as a VAS nausea rating \<25 mm.

The Functional Living Index-Emesis questionnaire (FLIE) is a validated, participant-reported instrument to measure the impact of chemotherapy-induced nausea and vomiting on daily life. There are 9 nausea-related items and 9 vomiting-related items, each on a 7-point scale. For the purposes of this study, "No Impact" on daily life was defined as an average item score of \>6 on the 7-point scale; a total score \>108 indicates no impact on daily life. Overall Stage=0 to 120 hours after initiation of MEC.

The percentage of participants who used no rescue therapy after initiation of MEC is presented for the Overall, Acute and Delayed Stages. Overall Stage=0 to 120 hours after initiation of MEC. Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.

An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition, which is temporally associated with the use of the study drug, is also an adverse event. Nausea and vomiting experienced during Days 1-6 were not counted as adverse events unless they were reported as a serious adverse event.

A vomiting episode was defined as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retches (an attempt to vomit that is not productive of stomach contents). Acute Stage=0 to 24 hours after initiation of MEC. Delayed Stage=25 to 120 hours after initiation of MEC.

Merck Sharp & Dohme LLC

The safety population consisted of all randomized participants who received chemotherapy and took ≥1 dose of study drug. Nausea and vomiting experienced during Days 1-6 were not counted as adverse events unless they were reported as a serious adverse event.

Participants receive one aprepitant 125 mg capsule PO QD on Day 1 and one aprepitant 80 mg capsule PO QD on Days 2 and 3 of Cycle 1. Participants also receive ondansetron 16 mg IV QD and dexamethasone 12 mg PO on Day 1 and placebo for ondansetron 8 mg PO BID on Days 2 and 3.

Aprepitant Regimen

Control Regimen

Total

20 to 29 years

30 to 39 years

40 to 49 years

50 to 59 years

60 to 69 years

≥70 years

Age, Customized

Sex: Female, Male

The Baseline Analysis Population consists of All Treated Participants. Two participants in each treatment group did not receive study drug.

Senior Vice President, Global Clinical Development

The modified intention-to-treat (mITT) population consisted of all randomized participants who received chemotherapy, took ≥1 dose of study drug and had ≥1 post-treatment assessment on Day 1 and Day 2.

The Percentage of Participants With No Vomiting - Overall Stage

Overall Stage

Acute Stage

Delayed Stage

The mITT population consisted of all randomized participants who received chemotherapy, took ≥1 dose of study drug and had ≥1 post-treatment assessment on Day 1 and Day 2.

Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages

Number of Emetic Events - Overall Stage

Percentage of Participants With No Vomiting and No Significant Nausea - Overall Stage

The mITT population consisted of all randomized participants who received chemotherapy, took ≥1 dose of study drug, had ≥1 post-treatment assessment on Day 1 and Day 2 and completed the FLIE questionnaire on Day 6.

Percentage of Participants With No Impact on Daily Life - Overall Stage

Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages

All randomized participants who received chemotherapy and took ≥1 dose of study drug.

Spots Global Cancer Trial Database for rescue therapy (granisetron, dolasetron, tropisetron or ondansetron; metoclopramide or alizapride).