Trial Outcomes & Findings for 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) (NCT NCT01636947)

Last Updated: 2018-09-25

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

494 participants

Primary outcome timeframe

Hour 0 on Day 1 to Day 5 (approximately 120 hours)

Results posted on

2018-09-25

Participant Flow

Participant milestones

Participant milestones
Measure	Aprepitant Regimen 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.	Control Regimen 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.
Overall Study STARTED	244	250
Overall Study Treated	242	248
Overall Study COMPLETED	232	239
Overall Study NOT COMPLETED	12	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Aprepitant Regimen 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.	Control Regimen 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.
Overall Study Not Treated	2	2
Overall Study Lost to Follow-up	4	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	3	3
Overall Study Adverse Event	1	1
Overall Study Did Not Meet Eligibility Criteria	1	4

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aprepitant Regimen n=242 Participants 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.	Control Regimen n=248 Participants 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.	Total n=490 Participants Total of all reporting groups
Age, Customized 20 to 29 years	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Age, Customized 30 to 39 years	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized 40 to 49 years	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Age, Customized 50 to 59 years	73 Participants n=5 Participants	65 Participants n=7 Participants	138 Participants n=5 Participants
Age, Customized 60 to 69 years	74 Participants n=5 Participants	77 Participants n=7 Participants	151 Participants n=5 Participants
Age, Customized ≥70 years	54 Participants n=5 Participants	65 Participants n=7 Participants	119 Participants n=5 Participants
Sex: Female, Male Female	108 Participants n=5 Participants	111 Participants n=7 Participants	219 Participants n=5 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	137 Participants n=7 Participants	271 Participants n=5 Participants

PRIMARY outcome

Timeframe: Hour 0 on Day 1 to Day 5 (approximately 120 hours)

Population: 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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=237 Participants 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.	Control Regimen n=243 Participants 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.
The Percentage of Participants With No Vomiting - Overall Stage	77.2 Percentage of Participants	72.0 Percentage of Participants

SECONDARY outcome

Timeframe: Hour 0 on Day 1 to Day 5 (approximately 120 hours)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=237 Participants 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.	Control Regimen n=243 Participants 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.
Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages Overall Stage	73.4 Percentage of Participants	70.4 Percentage of Participants
Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages Acute Stage	95.8 Percentage of Participants	97.9 Percentage of Participants
Percentage of Participants With a Complete Response - Overall, Acute, and Delayed Stages Delayed Stage	74.3 Percentage of Participants	71.2 Percentage of Participants

SECONDARY outcome

Timeframe: Hour 0 on Day 1 to Day 5 (approximately 120 hours)

Population: 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.

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

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=237 Participants 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.	Control Regimen n=243 Participants 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.
Number of Emetic Events - Overall Stage	54 Number of Emetic Events	68 Number of Emetic Events

SECONDARY outcome

Timeframe: Days 1 to Day 5

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=237 Participants 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.	Control Regimen n=243 Participants 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.
Percentage of Participants With No Vomiting and No Significant Nausea - Overall Stage	76.4 Percentage of Participants	72.4 Percentage of Participants

SECONDARY outcome

Timeframe: Day 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=233 Participants 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.	Control Regimen n=237 Participants 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.
Percentage of Participants With No Impact on Daily Life - Overall Stage	76.8 Percentage of Participants	73.8 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 to Day 5

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=237 Participants 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.	Control Regimen n=243 Participants 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.
Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages Overall Stage	84.8 Percentage of Participants	87.7 Percentage of Participants
Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages Acute Stage	98.7 Percentage of Participants	99.2 Percentage of Participants
Number of Participants With No Use of a Rescue Therapy - Overall, Acute, and Delayed Stages Delayed Stage	84.8 Percentage of Participants	88.5 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1 through Day 29 (Up to 28 days after first dose of study drug)

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

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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=242 Participants 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.	Control Regimen n=248 Participants 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.
Percentage of Participants With One or More Clinical Adverse Event	56.2 Percentage of Participants	53.2 Percentage of Participants

SECONDARY outcome

Timeframe: Day 1, Day 2 to Day 5

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Aprepitant Regimen n=237 Participants 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.	Control Regimen n=243 Participants 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.
Percentage of Participants With No Vomiting - Acute and Delayed Stages Acute Stage	95.8 Percentage of Participants	98.8 Percentage of Participants
Percentage of Participants With No Vomiting - Acute and Delayed Stages Delayed Stage	78.5 Percentage of Participants	72.4 Percentage of Participants

Adverse Events

Aprepitant Regimen

Serious events: 25 serious events

Other events: 87 other events

Deaths: 0 deaths

Control Regimen

Serious events: 16 serious events

Other events: 96 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Aprepitant Regimen n=242 participants at risk 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.	Control Regimen n=248 participants at risk 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.
Gastrointestinal disorders Constipation	4.1% 10/242 • Number of events 10 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	8.9% 22/248 • Number of events 22 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Gastrointestinal disorders Diarrhoea	5.8% 14/242 • Number of events 15 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	6.9% 17/248 • Number of events 17 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Gastrointestinal disorders Nausea	8.3% 20/242 • Number of events 20 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	8.1% 20/248 • Number of events 20 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Investigations Neutrophil count decreased	9.1% 22/242 • Number of events 22 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	8.5% 21/248 • Number of events 21 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Metabolism and nutrition disorders Decreased appetite	5.8% 14/242 • Number of events 15 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	6.0% 15/248 • Number of events 15 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Musculoskeletal and connective tissue disorders Myalgia	4.5% 11/242 • Number of events 11 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	7.3% 18/248 • Number of events 18 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Respiratory, thoracic and mediastinal disorders Hiccups	6.2% 15/242 • Number of events 15 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	2.4% 6/248 • Number of events 7 • Up to 28 days after first dose of study drug (Up to 29 days) 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.
Skin and subcutaneous tissue disorders Alopecia	3.7% 9/242 • Number of events 9 • Up to 28 days after first dose of study drug (Up to 29 days) 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.	6.9% 17/248 • Number of events 17 • Up to 28 days after first dose of study drug (Up to 29 days) 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.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER