Trial Outcomes & Findings for A Study of the Safety and Efficacy of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants (MK-0869-208) (NCT NCT01362530)

Last Updated: 2018-09-25

Results Overview

Delayed Phase was defined as 25-120 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the delayed phase of Cycle 1.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

307 participants

Primary outcome timeframe

25 to 120 hours after the start of chemotherapy

Results posted on

2018-09-25

Participant Flow

The base study consisted of once cycle of treatment (Cycle 1). Participants in either treatment group who met the eligibility criteria were eligible to participate in optional open-label aprepitant treatment for an additional 5 cycles (Cycles 2-6).

Participant milestones

Participant milestones
Measure	Aprepitant Regimen Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Control Regimen Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Base Study (Cycle 1) STARTED	155	152
Base Study (Cycle 1) Received Study Treatment	152	150
Base Study (Cycle 1) COMPLETED	150	149
Base Study (Cycle 1) NOT COMPLETED	5	3
Optional Extension (Cycles 2-6) STARTED	171	0
Optional Extension (Cycles 2-6) COMPLETED	46	0
Optional Extension (Cycles 2-6) NOT COMPLETED	125	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Aprepitant Regimen Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Control Regimen Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Base Study (Cycle 1) Adverse Event	2	0
Base Study (Cycle 1) Physician Decision	0	1
Base Study (Cycle 1) Protocol Violation	2	0
Base Study (Cycle 1) Withdrawal by Subject	1	2
Optional Extension (Cycles 2-6) Adverse Event	2	0
Optional Extension (Cycles 2-6) Completed Chemotherapy Regimen	51	0
Optional Extension (Cycles 2-6) Did Not Meet Additional Criteria	25	0
Optional Extension (Cycles 2-6) Did Not Respond To Chemotherapy Regimen	4	0
Optional Extension (Cycles 2-6) Lack of Efficacy	1	0
Optional Extension (Cycles 2-6) Lost to Follow-up	1	0
Optional Extension (Cycles 2-6) Physician Decision	19	0
Optional Extension (Cycles 2-6) Protocol Violation	4	0
Optional Extension (Cycles 2-6) Withdrawal by Subject	18	0

Baseline Characteristics

A Study of the Safety and Efficacy of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Pediatric Participants (MK-0869-208)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aprepitant Regimen n=152 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Control Regimen n=150 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Total n=302 Participants Total of all reporting groups
Age, Continuous	97.7 Months STANDARD_DEVIATION 63.2 • n=5 Participants	99.4 Months STANDARD_DEVIATION 60.9 • n=7 Participants	98.5 Months STANDARD_DEVIATION 62.0 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	71 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	79 Participants n=7 Participants	163 Participants n=5 Participants

PRIMARY outcome

Timeframe: 25 to 120 hours after the start of chemotherapy

Population: Intent-to-treat (ITT) population: all randomized participants who received study medication. Results for Cycles 2-6 were not included because this outcome measure is for Cycle 1 only.

Delayed Phase was defined as 25-120 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the delayed phase of Cycle 1.

Outcome measures

Outcome measures
Measure	Control Regimen n=150 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Aprepitant Regimen n=152 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Percentage of Participants With a Complete Response in the Delayed Phase of Cycle 1	26.0 Percentage of participants	50.7 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours after initiation of chemotherapy

Population: ITT population: all randomized participants who received study medication. Results for Cycles 2-6 were not included because this outcome measure is for Cycle 1 only.

Acute phase was defined as 0 to 24 hours after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the acute phase of Cycle 1.

Outcome measures

Outcome measures
Measure	Control Regimen n=150 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Aprepitant Regimen n=152 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Percentage of Participants With a Complete Response in the Acute Phase of Cycle 1	52.0 Percentage of participants	66.4 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 120 hours after initiation of chemotherapy

Population: ITT population: all randomized participants who received study medication. Results for Cycles 2-6 were not included because this outcome measure is for Cycle 1 only.

Overall phase was defined as 0 to 120 hourse after the start of chemotherapy. Complete response was defined as no vomiting or retching and no use of rescue medication in the overall phase of Cycle 1.

Outcome measures

Outcome measures
Measure	Control Regimen n=150 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Aprepitant Regimen n=152 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Percentage of Participants With a Complete Response in the Overall Phase of Cycle 1	20.0 Percentage of participants	40.1 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 120 hours after initiation of chemotherapy

Population: ITT population: all randomized participants who received study medication. Results for Cycles 2-6 were not included because this outcome measure is for Cycle 1 only.

Overall phase was defined as 0 to 120 hourse after the start of chemotherapy. No vomiting was defined as no emesis or retching or dry heaves in the overall phase of Cycle 1.

Outcome measures

Outcome measures
Measure	Control Regimen n=150 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.	Aprepitant Regimen n=152 Participants Cycle 1: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg). Optional Cycles 2-6: Open-label aprepitant administered in the same manner as in Cycle 1.
Percentage of Participants With No Vomiting in the Overall Phase of Cycle 1	21.3 Percentage of participants	46.7 Percentage of participants

Adverse Events

Aprepitant Regimen Cycle 1

Serious events: 46 serious events

Other events: 88 other events

Deaths: 0 deaths

Control Regimen Cycle 1

Serious events: 41 serious events

Other events: 84 other events

Deaths: 0 deaths

Aprepitant Regimen Cycles 2-6

Serious events: 84 serious events

Other events: 136 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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. Any information identified by the Sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Aprepitant Regimen Cycle 1 n=152 participants at risk Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).	Control Regimen Cycle 1 n=150 participants at risk Participants 12 to 17 years of age, Day 1: matching placebo for aprepitant 125 mg capsule oral (PO) + ondansetron Days 2 to 3: matching placebo for aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: matching placebo PFS: 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: matching placebo PFS: 2.0 mg/kg (up to 80 mg).	Aprepitant Regimen Cycles 2-6 n=170 participants at risk Participants completing Cycle 1 from either the aprepitant or the control regimen who meet eligibility criteria: Participants 12 to 17 years of age, Day 1: aprepitant 125 mg capsule orally (PO) + ondansetron, Days 2 to 3: aprepitant 80 mg capsule PO. Participants 6 months to \<12 years of age, Day 1: aprepitant powder for suspension (PFS), 3.0 mg/kg (up to 125 mg) + ondansetron, Days 2 to 3: aprepitant PFS, 2.0 mg/kg (up to 80 mg).
Blood and lymphatic system disorders Anaemia	15.8% 24/152 • Number of events 25 Intent-to-treat (ITT) population: all randomized participants who received study medication.	23.3% 35/150 • Number of events 38 Intent-to-treat (ITT) population: all randomized participants who received study medication.	36.5% 62/170 • Number of events 134 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Blood and lymphatic system disorders Leukopenia	5.3% 8/152 • Number of events 9 Intent-to-treat (ITT) population: all randomized participants who received study medication.	6.7% 10/150 • Number of events 11 Intent-to-treat (ITT) population: all randomized participants who received study medication.	7.6% 13/170 • Number of events 22 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Blood and lymphatic system disorders Neutropenia	11.2% 17/152 • Number of events 17 Intent-to-treat (ITT) population: all randomized participants who received study medication.	12.0% 18/150 • Number of events 20 Intent-to-treat (ITT) population: all randomized participants who received study medication.	22.9% 39/170 • Number of events 74 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Blood and lymphatic system disorders Thrombocytopenia	9.9% 15/152 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.	9.3% 14/150 • Number of events 16 Intent-to-treat (ITT) population: all randomized participants who received study medication.	22.4% 38/170 • Number of events 80 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Abdominal pain	7.2% 11/152 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.	6.7% 10/150 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.	10.0% 17/170 • Number of events 26 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/152 Intent-to-treat (ITT) population: all randomized participants who received study medication.	0.67% 1/150 • Number of events 1 Intent-to-treat (ITT) population: all randomized participants who received study medication.	5.9% 10/170 • Number of events 12 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Constipation	2.0% 3/152 • Number of events 3 Intent-to-treat (ITT) population: all randomized participants who received study medication.	4.0% 6/150 • Number of events 6 Intent-to-treat (ITT) population: all randomized participants who received study medication.	7.1% 12/170 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Diarrhoea	5.3% 8/152 • Number of events 11 Intent-to-treat (ITT) population: all randomized participants who received study medication.	5.3% 8/150 • Number of events 8 Intent-to-treat (ITT) population: all randomized participants who received study medication.	9.4% 16/170 • Number of events 23 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Nausea	8.6% 13/152 • Number of events 20 Intent-to-treat (ITT) population: all randomized participants who received study medication.	11.3% 17/150 • Number of events 20 Intent-to-treat (ITT) population: all randomized participants who received study medication.	24.7% 42/170 • Number of events 78 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Stomatitis	3.3% 5/152 • Number of events 6 Intent-to-treat (ITT) population: all randomized participants who received study medication.	2.7% 4/150 • Number of events 4 Intent-to-treat (ITT) population: all randomized participants who received study medication.	7.1% 12/170 • Number of events 16 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Gastrointestinal disorders Vomiiting	13.8% 21/152 • Number of events 31 Intent-to-treat (ITT) population: all randomized participants who received study medication.	13.3% 20/150 • Number of events 21 Intent-to-treat (ITT) population: all randomized participants who received study medication.	34.7% 59/170 • Number of events 152 Intent-to-treat (ITT) population: all randomized participants who received study medication.
General disorders Mucosal inflammation	0.66% 1/152 • Number of events 1 Intent-to-treat (ITT) population: all randomized participants who received study medication.	3.3% 5/150 • Number of events 5 Intent-to-treat (ITT) population: all randomized participants who received study medication.	6.5% 11/170 • Number of events 13 Intent-to-treat (ITT) population: all randomized participants who received study medication.
General disorders Pyrexia	5.3% 8/152 • Number of events 8 Intent-to-treat (ITT) population: all randomized participants who received study medication.	6.7% 10/150 • Number of events 10 Intent-to-treat (ITT) population: all randomized participants who received study medication.	12.9% 22/170 • Number of events 27 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Investigations Haemoglobin decreased	5.3% 8/152 • Number of events 9 Intent-to-treat (ITT) population: all randomized participants who received study medication.	4.0% 6/150 • Number of events 7 Intent-to-treat (ITT) population: all randomized participants who received study medication.	8.2% 14/170 • Number of events 27 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Investigations Neutrophil count decreased	7.9% 12/152 • Number of events 12 Intent-to-treat (ITT) population: all randomized participants who received study medication.	11.3% 17/150 • Number of events 19 Intent-to-treat (ITT) population: all randomized participants who received study medication.	18.8% 32/170 • Number of events 83 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Investigations Plastelet count decreased	6.6% 10/152 • Number of events 10 Intent-to-treat (ITT) population: all randomized participants who received study medication.	10.0% 15/150 • Number of events 16 Intent-to-treat (ITT) population: all randomized participants who received study medication.	15.3% 26/170 • Number of events 58 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Investigations White blood cell count decreased	3.3% 5/152 • Number of events 5 Intent-to-treat (ITT) population: all randomized participants who received study medication.	4.0% 6/150 • Number of events 6 Intent-to-treat (ITT) population: all randomized participants who received study medication.	7.1% 12/170 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Nervous system disorders Headache	7.2% 11/152 • Number of events 11 Intent-to-treat (ITT) population: all randomized participants who received study medication.	4.7% 7/150 • Number of events 7 Intent-to-treat (ITT) population: all randomized participants who received study medication.	8.2% 14/170 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Respiratory, thoracic and mediastinal disorders Cough	5.9% 9/152 • Number of events 9 Intent-to-treat (ITT) population: all randomized participants who received study medication.	3.3% 5/150 • Number of events 6 Intent-to-treat (ITT) population: all randomized participants who received study medication.	10.6% 18/170 • Number of events 25 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 3/152 • Number of events 3 Intent-to-treat (ITT) population: all randomized participants who received study medication.	2.0% 3/150 • Number of events 3 Intent-to-treat (ITT) population: all randomized participants who received study medication.	5.9% 10/170 • Number of events 15 Intent-to-treat (ITT) population: all randomized participants who received study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.3% 2/152 • Number of events 2 Intent-to-treat (ITT) population: all randomized participants who received study medication.	0.67% 1/150 • Number of events 1 Intent-to-treat (ITT) population: all randomized participants who received study medication.	6.5% 11/170 • Number of events 11 Intent-to-treat (ITT) population: all randomized participants who received study medication.