Trial Outcomes & Findings for Efficacy and Safety Study of Fosaprepitant (MK-0517) Plus Ondansetron Versus Ondansetron Alone for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Participants (MK-0517-044) (NCT NCT02519842)

NCT ID: NCT02519842

Last Updated: 2019-03-15

Results Overview

Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the delayed phase, defined as the time period of \>24 to120 hours post initiation of chemotherapy in Cycle 1, was calculated.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 75 participants
• Primary outcome timeframe: >24 to 120 hours post initiation of chemotherapy (1 to 15 days after the dose of study drug)
• Results posted on: 2019-03-15

Participant Flow

Eligible participants for chemotherapy Cycles 1-6 were 0-17 years old and had documented malignancies and were scheduled to receive chemotherapeutic agent(s) associated with moderate or high risk of emetogenicity. Participants entering Cycles 2-6 must have completed Cycle 1 and had no unresolved drug-related adverse events.

Participants received double-blinded fosaprepitant+ondansetron with/without dexamethasone OR placebo + ondansetron with/without dexamethasone in Cycle 1. Upon completion of Cycle 1, participants from both Cycle 1 arms had the option to continue for 5 cycles of open-label fosaprepitant + 5-hydroxytryptamine 3 antagonist with/without dexamethasone.

Participant milestones

Measure	Fosaprepitant Regimen Cycle 1 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-hydroxytryptamine 3 (5-HT3) antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Base Study: Cycle 1 STARTED	38	37	0
Base Study: Cycle 1 Treated	37	34	0
Base Study: Cycle 1 COMPLETED	36	34	0
Base Study: Cycle 1 NOT COMPLETED	2	3	0
Optional Extension: Cycles 2-6 STARTED	0	0	55
Optional Extension: Cycles 2-6 Treated	0	0	55
Optional Extension: Cycles 2-6 COMPLETED	0	0	26
Optional Extension: Cycles 2-6 NOT COMPLETED	0	0	29

Reasons for withdrawal

Measure	Fosaprepitant Regimen Cycle 1 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-hydroxytryptamine 3 (5-HT3) antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Base Study: Cycle 1 Screening Failure	1	1	0
Base Study: Cycle 1 Adverse Event	1	0	0
Base Study: Cycle 1 Withdrawn by Parent/Guardian	0	1	0
Base Study: Cycle 1 Non-compliance with Study Drug	0	1	0
Optional Extension: Cycles 2-6 Physician Decision	0	0	5
Optional Extension: Cycles 2-6 Adverse Event	0	0	1
Optional Extension: Cycles 2-6 Withdrawal by Parent/Guardian	0	0	3
Optional Extension: Cycles 2-6 Withdrawal by Subject	0	0	1
Optional Extension: Cycles 2-6 Death	0	0	1
Optional Extension: Cycles 2-6 Did Not Respond to Chemotherapy	0	0	2
Optional Extension: Cycles 2-6 Completed Chemotherapy	0	0	13
Optional Extension: Cycles 2-6 Enrollment Terminated at Site	0	0	1
Optional Extension: Cycles 2-6 Cycle Eligibility Criteria Not Met	0	0	2

Baseline Characteristics

Efficacy and Safety Study of Fosaprepitant (MK-0517) Plus Ondansetron Versus Ondansetron Alone for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Pediatric Participants (MK-0517-044)

Baseline characteristics by cohort

Measure	Fosaprepitant Regimen Cycle 1 n=38 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=37 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Total n=75 Participants Total of all reporting groups
Age, Continuous	10.8 Years STANDARD_DEVIATION 4.2 • n=5 Participants	10.9 Years STANDARD_DEVIATION 4.4 • n=7 Participants	10.9 Years STANDARD_DEVIATION 4.3 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	21 Participants n=7 Participants	45 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	28 Participants n=7 Participants	56 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: >24 to 120 hours post initiation of chemotherapy (1 to 15 days after the dose of study drug)

Population: All participants who received at least 1 dose of study drug during Cycle 1.

Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the delayed phase, defined as the time period of >24 to120 hours post initiation of chemotherapy in Cycle 1, was calculated.

Outcome measures

Measure	Fosaprepitant Regimen Cycle 1 n=37 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-HT3 antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Percentage of Participants Who Experienced a Complete Response During the Delayed Phase (>24 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1	48.6 Percentage of Participants	41.2 Percentage of Participants	—

PRIMARY outcome

Timeframe: Up to 6.5 months (up to 2 weeks after last dose of study drug)

Population: All participants who received at least 1 dose of study drug.

An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. A statistical analysis was performed for Tier 2 AEs in Cycle 1 to compare the percentage of participants who received fosaprepitant regimen and experienced at least 1 Tier 2 AE compared with the percentage of participants in the control regimen. The Tier 2 endpoint included broad clinical and laboratory AE categories consisting of the percentage of participants with any AE, drug-related AE, serious AE, and AEs that are both drug-related and serious. Tier 2 AEs were not pre-specified as events of interest and inclusion in the Tier 2 analysis required that at least 4 participants in any treatment group exhibited the AE.

Outcome measures

Measure	Fosaprepitant Regimen Cycle 1 n=37 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 n=55 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-HT3 antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Percentage of Participants Who Experienced One or More Adverse Events	89.2 Percentage of Participants	79.4 Percentage of Participants	78.2 Percentage of Participants

PRIMARY outcome

Timeframe: Up to 6 months (up to last dose of study drug)

Population: All participants who received at least 1 dose of study drug.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug. A statistical analysis was performed to compare the percentage of participants who discontinued in Cycle 1 due to an AE and received fosaprepitant regimen compared with the percentage of participants who received control regimen.

Outcome measures

Measure	Fosaprepitant Regimen Cycle 1 n=37 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 n=55 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-HT3 antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event	5.4 Percentage of Participants	0.0 Percentage of Participants	0.0 Percentage of Participants

SECONDARY outcome

Timeframe: 0 to 24 hours post initiation of chemotherapy (up to 1 day after the dose of study drug)

Population: All participants who received at least 1 dose of study drug during Cycle 1.

Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the acute phase, defined as the time period of 0 to 24 hours post initiation of chemotherapy in Cycle 1, was calculated.

Outcome measures

Measure	Fosaprepitant Regimen Cycle 1 n=37 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-HT3 antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Percentage of Participants Who Experienced a Complete Response During the Acute Phase (0 to 24 Hours Post Initiation of Chemotherapy) in Cycle 1	70.3 Percentage of Participants	58.8 Percentage of Participants	—

SECONDARY outcome

Timeframe: 0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)

Population: All participants who received at least 1 dose of study drug during Cycle 1.

Complete Response was defined as no vomiting, no retching, and no use of rescue medication following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. The percentage of participants with no vomiting and no retching episodes in the overall phase, defined as the time period of 0 to 120 hours post initiation of chemotherapy in Cycle 1, was calculated.

Outcome measures

Measure	Fosaprepitant Regimen Cycle 1 n=37 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-HT3 antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Percentage of Participants Who Experienced a Complete Response During the Overall Phase (0 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1	40.5 Percentage of Participants	32.4 Percentage of Participants	—

SECONDARY outcome

Timeframe: 0 to 120 hours post initiation of chemotherapy (up to 15 days after the dose of study drug)

Population: All participants who received at least 1 dose of study drug during Cycle 1.

Vomiting was assessed, regardless of rescue medicine use, following the initiation of emetogenic chemotherapy in Cycle 1. A vomiting episode was specified as one or more episodes of emesis (expulsion of stomach contents through the mouth) or retching/dry heaves (an attempt to vomit that is not productive of stomach contents). Distinct vomiting episodes were separated by the absence of emesis and retching for at least one minute. The date and time of each vomiting episode was recorded by participants in diaries at the time of occurrence. Rescue medication was permitted to alleviate symptoms of established nausea or vomiting; but not as preventive medication. The percentage of participants with no vomiting and no retching episodes in the overall phase, defined as the time period of 0 to 120 hours post initiation of chemotherapy in Cycle 1, was calculated.

Outcome measures

Measure	Fosaprepitant Regimen Cycle 1 n=37 Participants Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 Participants Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-HT3 antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Percentage of Participants Who Experienced No Vomiting, Regardless of Rescue Medication Use, During the Overall Phase (0 to 120 Hours Post Initiation of Chemotherapy) in Cycle 1	40.5 Percentage of Participants	32.4 Percentage of Participants	—

Adverse Events

Fosaprepitant Regimen Cycle 1

Serious events: 11 serious events

Other events: 28 other events

Deaths: 0 deaths

Control Regimen Cycle 1

Serious events: 8 serious events

Other events: 18 other events

Deaths: 0 deaths

Fosaprepitant Regimen Cycles 2-6

Serious events: 28 serious events

Other events: 30 other events

Deaths: 1 deaths

Serious adverse events

Measure	Fosaprepitant Regimen Cycle 1 n=37 participants at risk Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 participants at risk Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 n=55 participants at risk Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-hydroxytryptamine 3 (5-HT3) antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Blood and lymphatic system disorders Anaemia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Bone marrow failure	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.5% 3/55 • Number of events 6 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Febrile neutropenia	10.8% 4/37 • Number of events 4 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	14.7% 5/34 • Number of events 5 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	34.5% 19/55 • Number of events 32 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Leukopenia	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Neutropenia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Pancytopenia	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Cardiac disorders Tachycardia	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Colitis	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Proctalgia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Vomiting	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Complication associated with device	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders General physical health deterioration	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Mucosal inflammation	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Pyrexia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Soft tissue inflammation	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Immune system disorders Hypersensitivity	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Appendicitis	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Bacteraemia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Catheter site infection	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Influenza	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Klebsiella bacteraemia	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Otitis media chronic	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Infections and infestations Sepsis	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Investigations Amylase increased	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Metabolism and nutrition disorders Dehydration	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Metabolism and nutrition disorders Diet refusal	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Musculoskeletal and connective tissue disorders Soft tissue mass	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Nervous system disorders Seizure	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Product Issues Thrombosis in device	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.

Other adverse events

Measure	Fosaprepitant Regimen Cycle 1 n=37 participants at risk Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Control Regimen Cycle 1 n=34 participants at risk Participants received a single dose of matched placebo for fosaprepitant IV on Day 1 prior to chemotherapy plus ondansetron IV on Day 1 prior to chemotherapy and at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy. Participants may have also received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.	Fosaprepitant Regimen Cycles 2-6 n=55 participants at risk Participants received a single dose of fosaprepitant 150 mg (or age-based adjustment) IV on Day 1 prior to chemotherapy plus a 5-hydroxytryptamine 3 (5-HT3) antagonist on Day 1 prior to chemotherapy and per product label or standard of care. Participants may also have received dexamethasone IV at investigator's discretion on day(s) of chemotherapy and up to 24 hours after chemotherapy.
Blood and lymphatic system disorders Anaemia	29.7% 11/37 • Number of events 11 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	8.8% 3/34 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	20.0% 11/55 • Number of events 20 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Febrile neutropenia	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.9% 2/34 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Leukopenia	13.5% 5/37 • Number of events 5 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	12.7% 7/55 • Number of events 15 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Neutropenia	13.5% 5/37 • Number of events 6 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	8.8% 3/34 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	7.3% 4/55 • Number of events 5 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Blood and lymphatic system disorders Thrombocytopenia	21.6% 8/37 • Number of events 8 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.9% 2/34 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	12.7% 7/55 • Number of events 14 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Abdominal pain	10.8% 4/37 • Number of events 4 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	10.9% 6/55 • Number of events 9 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Constipation	8.1% 3/37 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.9% 2/34 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	9.1% 5/55 • Number of events 6 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Diarrhoea	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Nausea	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	16.4% 9/55 • Number of events 14 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Proctalgia	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.5% 3/55 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Stomatitis	2.7% 1/37 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.5% 3/55 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Gastrointestinal disorders Vomiting	10.8% 4/37 • Number of events 4 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	20.0% 11/55 • Number of events 24 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Fatigue	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.9% 2/34 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Mucosal inflammation	8.1% 3/37 • Number of events 4 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	7.3% 4/55 • Number of events 6 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
General disorders Pyrexia	10.8% 4/37 • Number of events 5 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	12.7% 7/55 • Number of events 8 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Investigations Alanine aminotransferase increased	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	8.8% 3/34 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.5% 3/55 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Investigations Aspartate aminotransferase increased	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.9% 2/34 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Investigations Neutrophil count decreased	16.2% 6/37 • Number of events 6 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	8.8% 3/34 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	3.6% 2/55 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Investigations Platelet count decreased	10.8% 4/37 • Number of events 4 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	8.8% 3/34 • Number of events 5 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	9.1% 5/55 • Number of events 32 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Musculoskeletal and connective tissue disorders Back pain	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/37 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	5.9% 2/34 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Musculoskeletal and connective tissue disorders Pain in extremity	2.7% 1/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	7.3% 4/55 • Number of events 4 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	1.8% 1/55 • Number of events 3 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Respiratory, thoracic and mediastinal disorders Hiccups	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	2.9% 1/34 • Number of events 1 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.
Skin and subcutaneous tissue disorders Rash	5.4% 2/37 • Number of events 2 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/34 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.	0.00% 0/55 • Adverse events data were collected up to 6.5 months (from start of study drug and up to 14 days after the last dose for each cycle in Cycles 1-6). This safety analysis was based on all participants who received at least 1 dose of study drug during Cycles 1 through 6. Cycle 1 is the base study. The participants who completed Cycle 1 were invited to participate in optional Cycles 2-6; there were no new participants enrolled.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

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 trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
• Publication restrictions are in place

Restriction type: OTHER