Trial Outcomes & Findings for A Study Of IV Casopitant For The Prevention Of Chemotherapy Induced Nausea And Vomiting. (NCT NCT00601172)

Last Updated: 2018-01-17

Results Overview

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase (0-120 hours) are presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

710 participants

Primary outcome timeframe

0 to 120 hours in the first cycle of chemotherapy

Results posted on

2018-01-17

Participant Flow

This study was conducted at 89 centers (55 centers in Europe, 30 in North America and 4 in Korea) in 11 countries from 10-March-2008 to 13-April-2009.

All participants received ondansetron and dexamethasone as background antiemetic therapy. To assure adequate blinding, placebo to match casopitant was used. Participants were screened within 14 days of first dose of study anti-emetics and were randomly assigned to either single dose intravenous (IV) (90 mg casopitant) or control (placebo).

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 milligram \[mg\] twice daily \[BID\] orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Overall Study STARTED	355	355
Overall Study COMPLETED	214	228
Overall Study NOT COMPLETED	141	127

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 milligram \[mg\] twice daily \[BID\] orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Overall Study Adverse Event	43	32
Overall Study Lack of Efficacy	11	12
Overall Study Protocol Violation	2	5
Overall Study Lost to Follow-up	4	3
Overall Study Physician Decision	27	28
Overall Study Withdrawal by Subject	35	27
Overall Study Did not meet continuation criteria	19	20

Baseline Characteristics

N=352

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=355 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Total n=710 Participants Total of all reporting groups
Age, Continuous	61.3 Years STANDARD_DEVIATION 10.77 • n=352 Participants • N=352	61.3 Years STANDARD_DEVIATION 11.03 • n=355 Participants • N=352	61.3 Years STANDARD_DEVIATION 10.90 • n=707 Participants • N=352
Sex: Female, Male Female	145 Participants n=355 Participants	173 Participants n=355 Participants	318 Participants n=710 Participants
Sex: Female, Male Male	210 Participants n=355 Participants	182 Participants n=355 Participants	392 Participants n=710 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=355 Participants	1 Participants n=355 Participants	1 Participants n=710 Participants
Race (NIH/OMB) Asian	24 Participants n=355 Participants	30 Participants n=355 Participants	54 Participants n=710 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=355 Participants	0 Participants n=355 Participants	0 Participants n=710 Participants
Race (NIH/OMB) Black or African American	5 Participants n=355 Participants	6 Participants n=355 Participants	11 Participants n=710 Participants
Race (NIH/OMB) White	326 Participants n=355 Participants	318 Participants n=355 Participants	644 Participants n=710 Participants
Race (NIH/OMB) More than one race	0 Participants n=355 Participants	0 Participants n=355 Participants	0 Participants n=710 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=355 Participants	0 Participants n=355 Participants	0 Participants n=710 Participants

PRIMARY outcome

Timeframe: 0 to 120 hours in the first cycle of chemotherapy

Population: Modified Intent-to-Treat Population (mITT) comprised of all participants who were randomized, received any investigational product and had oxaliplatin administered.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Achieved a Complete Response in the Overall Phase (0-120 Hours) Following Initiation of the First Cycle of an Oxaliplatin Based Moderately Emetogenic Chemotherapy (MEC) Regimen	85 Percentage of participants	86 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours in the first cycle of chemotherapy

Population: MITT Population.

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the acute phase of Cycle 1 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1	96 Percentage of participants	97 Percentage of participants

SECONDARY outcome

Timeframe: 24 to 120 hours (delayed phase) in the first cycle of chemotherapy

Population: MITT Population.

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the delayed phase of Cycle 1 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1	85 Percentage of participants	86 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 120 hours in the second cycle of chemotherapy

Population: MITT Population.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2	84 Percentage of participants	90 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population. Only those participants available at the specified time points were analyzed.

VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS) 0-120 hours	13.5 Scores on a Scale Standard Deviation 23.3	16.0 Scores on a Scale Standard Deviation 24.5
Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS) 0-24 hours	4.3 Scores on a Scale Standard Deviation 12.9	5.3 Scores on a Scale Standard Deviation 13.3
Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS) 24-120 hours	13.0 Scores on a Scale Standard Deviation 22.6	15.3 Scores on a Scale Standard Deviation 24.2

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Anti-emetic rescue medication was defined as medication that was administered specifically for the treatment of nausea and/or emesis during Days 1-6 of each cycle. The choice of rescue anti-emetic medication was left to the discretion of the investigator. Participants who required antiemetic rescue medication(s) during the 120-hour assessment period were considered treatment failures for that cycle. Percentage of participants who received rescue medication are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Received Rescue Medication 24-120 hours	9 Percentage of participants	8 Percentage of participants
Percentage of Participants Who Received Rescue Medication 0-120 hours	9 Percentage of participants	8 Percentage of participants
Percentage of Participants Who Received Rescue Medication 0-24 hours	2 Percentage of participants	1 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that is not productive of gastrointestinal contents (also known as dry heaves). If a participant took rescue medication but there was no evidence of vomiting or retching, then the participant was considered as not having vomited. Percentage of participants who vomited and/or retched during the first 120 hours of the first cycle of chemotherapy are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Vomited and/or Retched 0-120 hours	11 Percentage of participants	10 Percentage of participants
Percentage of Participants Who Vomited and/or Retched 0-24 hours	3 Percentage of participants	2 Percentage of participants
Percentage of Participants Who Vomited and/or Retched 24-120 hours	11 Percentage of participants	10 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported significant nausea, defined as a maximum score \>= 25 mm on the VAS are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS 0-120 hours	19 Percentage of participants	21 Percentage of participants
Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS 0-24 hours	4 Percentage of participants	5 Percentage of participants
Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS 24-120 hours	19 Percentage of participants	21 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported nausea, defined as a maximum score of \>= 5 mm on the VAS are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS 0-120 hours	37 Percentage of participants	45 Percentage of participants
Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS 0-24 hours	12 Percentage of participants	15 Percentage of participants
Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS 24-120 hours	37 Percentage of participants	45 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Complete protection was defined as no vomiting/retching, no use of rescue medication and no significant nausea. Percentage of participants who achieved complete protection or complete responders with no significant nausea are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea 24-120 hours	75 Percentage of participants	74 Percentage of participants
Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea 0-120 hours	75 Percentage of participants	74 Percentage of participants
Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea 0-24 hours	93 Percentage of participants	93 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Total control was defined as no vomiting/retching, no use of rescue medication and no nausea. Percentage of participants who achieved total control or complete responders with no nausea are presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea 0-120 hours	61 Percentage of participants	54 Percentage of participants
Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea 0-24 hours	88 Percentage of participants	83 Percentage of participants
Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea 24-120 hours	61 Percentage of participants	54 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

FLIE questionnaire specifically addresses the impact of nausea and vomiting on daily activities (physical, social and emotional function, ability to enjoy meals). It consists of 18 items with questions divided into two domains: Nausea (questions 1-9) and Vomiting (questions 10-18). Each item is scored on a VAS with 7 hatch marks. The scale is anchored at 1 (Not at all) and 7 (A great deal). For questions 1,2,4,5,7,8-10,12-14,16 and 17 the final score was calculated by subtracting the initial score from 100 for questions 3,6,11,15 and 18 the final score was the one provided in the dataset. The score for the nausea domain: (\[sum of nausea item scores\] ÷ \[Number of items answered\] x 9) and for vomiting domain: (\[sum of vomiting item scores\] ÷ \[Number of items answered\] x 9). The total score was the sum of the nausea and vomiting domain scores. Higher scores indicate less impairment on daily life as a result of nausea or vomiting.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire Nausea impact	21.3 Percentage of participants	23.7 Percentage of participants
Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire Vomiting impact	12.5 Percentage of participants	11.5 Percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Participants were asked to rate the level of nausea he/she experienced over the previous (24 hours for a period of 120 hours following the administration of MEC), by placing a vertical mark on a VAS. The severity of nausea and was calculated by using a 0 - 100 VAS where 0 = No Nausea and 100 = Nausea as bad as it can be. The categorical scale assessed the participants severity of his/her nausea using the following: mild: Queasiness/upset stomach that is manageable and minimally (if at all) affects daily activities, moderate: increased queasiness, sometimes with the feeling of having to vomit/throw up (but not vomiting), that has significant negative effect on the daily activities (for example, being unable to work, eat and drink, prepare food, care for children or others) and severe: feeling sick and vomiting or feeling like you are going to vomit, and unable to perform most daily activities. Higher scores indicated worst outcome.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-120 hours · None	218 Participants	192 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-120 hours · Mild	73 Participants	97 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-120 hours · Moderate	49 Participants	54 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-120 hours · Severe	12 Participants	12 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-24 hours · None	313 Participants	299 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-24 hours · Mild	23 Participants	40 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-24 hours · Moderate	13 Participants	15 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 0-24 hours · Severe	3 Participants	1 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 24-120 hours · None	218 Participants	192 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 24-120 hours · Mild	73 Participants	97 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 24-120 hours · Moderate	49 Participants	54 Participants
Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale 24-120 hours · Severe	12 Participants	12 Participants

SECONDARY outcome

Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

Population: PK parameter population: All participants who consented to PK sampling, who were randomized to IV casopitant and for whom a PK sample was obtained and analyzed, and from whom sufficient data was available to calculate casopitant PK parameters on an as-treated basis. Only those participants with data available at indicated time points were analyzed.

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. AUC(0-∞), AUC(0-t), AUC(0-24) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 Casopitant: AUC(0-24)	6913.626 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 61.4868	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 Casopitant: AUC(0-inf)	8607.049 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 61.8698	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 Casopitant: AUC(0-t)	7688.562 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 58.9620	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 GSK525060: AUC(0-24)	2247.290 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 36.6378	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 GSK525060: AUC(0-t)	2796.734 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 36.6862	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 GSK517142: AUC(0-24)	49.964 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 40.5170	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 GSK517142: AUC(0-t)	40.997 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 126.8389	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 GSK631832: AUC(0-24)	165.550 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 38.6564	—
Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832 GSK631832: AUC(0-t)	231.018 Hournanogram/milliliter (hrng/mL) Geometric Coefficient of Variation 40.8915	—

SECONDARY outcome

Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

Population: PK Parameter population. Only those participants available at the specified time points were analyzed.

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. (Cmax) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 Casopitant	2078.776 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 144.8121	—
Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 GSK525060	143.038 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 32.7047	—
Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 GSK517142	3.426 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 45.1672	—
Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 GSK631832	9.853 Nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 35.8595	—

SECONDARY outcome

Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

Population: PK parameter population. Only those participants available at the specified time points were analyzed.

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Tmax and t1/2 for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 Casopitant: Tmax	0.520 Hour Interval 0.0 to 1.5	—
Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 Casopitant: t1/2	12.347 Hour Interval 5.68 to 28.76	—
Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 GSK525060: Tmax	3.580 Hour Interval 1.0 to 24.5	—
Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 GSK517142: Tmax	1.500 Hour Interval 0.58 to 24.5	—
Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832 GSK631832: Tmax	5.500 Hour Interval 3.48 to 24.67	—

SECONDARY outcome

Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. CL for casopitant is presented.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Single-dose Pharmacokinetic Parameters: Clearance (CL) for Casopitant	10.457 Liter/hour Geometric Coefficient of Variation 61.8700	—

SECONDARY outcome

Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Vdss for casopitant is presented.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Single-dose Pharmacokinetic Parameters: Volume of Distribution (Vdss) for Casopitant	126.776 Liter Geometric Coefficient of Variation 95.6229	—

SECONDARY outcome

Timeframe: Up to 35 days

Population: Safety Population which comprised of all participants who were randomized, and received any investigational product.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect. Any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK product was recorded from the time a participant consents to participate in the study up to and including any follow-up contact.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	176 Participants	171 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	23 Participants	26 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Day 24

Population: Safety Population.

Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the National Cancer Institute common toxicity criteria for adverse events (NCI-CTCAE), version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Hematology parameters assessed were hematocrit, hemoglobin, platelet count, total neutrophils and white blood cell count. Data has been presented for the number of participants with hematology toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hematocrit: All cycles, Grade 2 to Grade 3	0 Participants	1 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hemoglobin: All cycles, Grade 1 to Grade 3	2 Participants	0 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hemoglobin: All cycles, Grade 2 to Grade 3	3 Participants	1 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hemoglobin: All cycles, Grade 3 to Grade 3	0 Participants	2 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Platelet count: All cycles, Grade 0 to 3	1 Participants	1 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Total Neutrophils: All cycles, Grade 0 to 3	24 Participants	37 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Total Neutrophils: All cycles, Grade 1 to 3	0 Participants	1 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Total Neutrophils: All cycles, Grade 2 to 3	1 Participants	0 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 White Blood Cell count: All cycles, Grade 0 to 3	10 Participants	5 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 White Blood Cell count: All cycles, Grade 1 to 3	0 Participants	1 Participants
Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 White Blood Cell count: All cycles, Grade 2 to 3	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Day 24

Population: Safety Population.

Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the NCI-CTCAE, version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Clinical chemistry parameters assessed were alanine amino transferase (ALT), aspartate amino transferase (AST), chloride, glucose, potassium, sodium and total bilirubin. Data has been presented for the number of participants with chemistry toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperglycemia: Al cycles, Grade 0 to 3	1 Participants	3 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperglycemia: All cycles, Grade 1 to 3	1 Participants	2 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperglycemia: All cycles, Grade 2 to 3	9 Participants	5 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperglycemia: All cycles, Grade 3 to 3	3 Participants	3 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hypoglycemia: All cycles, Grade 0 to 4	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperkalemia: All cycles, Grade 2 to 3	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperkalemia: All cycles, Grade 4 to 3	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperkalemia: All cycles, Grade 0 to 3	0 Participants	2 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyperkalemia: All cycles, Grade 0 to 4	0 Participants	2 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hypokalemia: All cycles, Grade 0 to 3	6 Participants	8 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Hyponatremia: All cycles, Grade 1 to 3	6 Participants	8 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Total Bilirubin: All cycles, Grade 0 to 3	1 Participants	1 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Total Bilirubin: All cycles, Grade 0 to 4	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 ALT: All cycles, Grade 0 to 3	1 Participants	2 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 ALT: All cycles, Grade 2 to 3	1 Participants	0 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 AST: All cycles, Grade 0 to 3	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 High chloride: All cycles, Grade 1 to 3	2 Participants	0 Participants
Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4 Low chloride: All cycles, Grade 0 to 3	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to End of Cycle for 6 cycles, an average of 24 days per cycle

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Vital signs assessment included DBP and SBP. SBP and DBP were recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean SBP and DBP are presented.

Outcome measures

SECONDARY outcome

Timeframe: Up to End of Cycle for 6 cycles, an average of 24 days per cycle

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Vital sign included heart rate which was recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean heart rate is presented.

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Evaluation of Vital Signs: Mean Heart Rate Cycle 1, post-oxaliplatin	73.1 Beats/minute Standard Deviation 8.90	73.7 Beats/minute Standard Deviation 9.45
Evaluation of Vital Signs: Mean Heart Rate Cycle 1, End of cycle	75.1 Beats/minute Standard Deviation 9.65	75.3 Beats/minute Standard Deviation 9.91
Evaluation of Vital Signs: Mean Heart Rate Cycle 2, post-oxaliplatin	73.0 Beats/minute Standard Deviation 9.24	73.7 Beats/minute Standard Deviation 9.39
Evaluation of Vital Signs: Mean Heart Rate Cycle 2, End of cycle	74.8 Beats/minute Standard Deviation 9.48	74.7 Beats/minute Standard Deviation 9.79
Evaluation of Vital Signs: Mean Heart Rate Cycle 3, post-oxaliplatin	73.2 Beats/minute Standard Deviation 9.37	72.2 Beats/minute Standard Deviation 9.16
Evaluation of Vital Signs: Mean Heart Rate Cycle 3, End of cycle	74.9 Beats/minute Standard Deviation 9.24	75.4 Beats/minute Standard Deviation 10.56
Evaluation of Vital Signs: Mean Heart Rate Cycle 4, post-oxaliplatin	72.6 Beats/minute Standard Deviation 9.32	72.2 Beats/minute Standard Deviation 9.16
Evaluation of Vital Signs: Mean Heart Rate Cycle 4, End of cycle	75.0 Beats/minute Standard Deviation 10.02	74.7 Beats/minute Standard Deviation 9.36
Evaluation of Vital Signs: Mean Heart Rate Cycle 5, post-oxaliplatin	72.8 Beats/minute Standard Deviation 9.27	72.9 Beats/minute Standard Deviation 9.35
Evaluation of Vital Signs: Mean Heart Rate Cycle 5, End of cycle	74.7 Beats/minute Standard Deviation 10.29	75.0 Beats/minute Standard Deviation 9.10
Evaluation of Vital Signs: Mean Heart Rate Cycle 6, post-oxaliplatin	73.5 Beats/minute Standard Deviation 9.44	73.4 Beats/minute Standard Deviation 9.72
Evaluation of Vital Signs: Mean Heart Rate Cycle 6, End of cycle	74.7 Beats/minute Standard Deviation 8.52	75.6 Beats/minute Standard Deviation 10.22

SECONDARY outcome

Timeframe: 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Time to first rescue medication was defined as the length of time from initiation of oxaliplatin till the first reported use of a rescue medication. Participants withdrawing prematurely during the 120 hour assessment period without having received a rescue medication were assumed to have done so and the time of rescue medication was set to 0 hours. The first quartile for time to use of anti-emetic rescue medication was evaluated when 25th percentile of participants of MITT population reported use of anti-emetic rescue medication. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported use of anti-emetic rescue medication at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA).

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Time to First Anti-emetic Rescue Medication	NA Hours NA indicates 'median is not evaluable' as less than 25th percentile of participants reported use of anti-emetic rescue medication.	NA Hours NA indicates 'median is not evaluable' as less than 25th percentile of participants reported use of anti-emetic rescue medication.

SECONDARY outcome

Timeframe: 0 to 120 hours in the first cycle of chemotherapy

Population: MITT Population.

Time to first emetic event was defined as the length of time from initiation of oxaliplatin until the time of first emetic event. Participants withdrawing prematurely from the study without having experienced an emetic event were assumed to have done so and the time of emetic event was set to 0 hours. The first quartile for time to emetic event was evaluated when 25th percentile of participants of MITT population reported emetic event. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported emetic event at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA).

Outcome measures

Outcome measures
Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Time to First Emetic Event	NA Hours NA indicates 'median is not evaluable' as less than 25th percentile of participants reported emetic event.	NA Hours NA indicates 'median is not evaluable' as less than 25th percentile of participants reported emetic event.

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 237 other events

Deaths: 5 deaths

Casopitant 90 mg

Serious events: 26 serious events

Other events: 257 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=352 Participants Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 Participants Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 1, post-oxaliplatin	77.2 Millimeters of mercury (mmHg) Standard Deviation 8.21	76.5 Millimeters of mercury (mmHg) Standard Deviation 8.27
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 1, End of cycle	76.9 Millimeters of mercury (mmHg) Standard Deviation 9.34	76.5 Millimeters of mercury (mmHg) Standard Deviation 9.80
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 2, post-oxaliplatin	77.7 Millimeters of mercury (mmHg) Standard Deviation 8.83	76.8 Millimeters of mercury (mmHg) Standard Deviation 8.86
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 2, End of cycle	76.8 Millimeters of mercury (mmHg) Standard Deviation 9.01	77.1 Millimeters of mercury (mmHg) Standard Deviation 9.89
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 3, post-oxaliplatin	78.0 Millimeters of mercury (mmHg) Standard Deviation 9.57	76.6 Millimeters of mercury (mmHg) Standard Deviation 9.25
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 3, End of cycle	77.3 Millimeters of mercury (mmHg) Standard Deviation 8.64	77.2 Millimeters of mercury (mmHg) Standard Deviation 9.80
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 4, post-oxaliplatin	78.2 Millimeters of mercury (mmHg) Standard Deviation 8.98	76.9 Millimeters of mercury (mmHg) Standard Deviation 9.16
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 4, End of cycle	76.8 Millimeters of mercury (mmHg) Standard Deviation 8.41	76.4 Millimeters of mercury (mmHg) Standard Deviation 9.90
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 5, post-oxaliplatin	77.4 Millimeters of mercury (mmHg) Standard Deviation 8.44	77.7 Millimeters of mercury (mmHg) Standard Deviation 9.55
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 5, End of cycle	77.1 Millimeters of mercury (mmHg) Standard Deviation 8.03	77.7 Millimeters of mercury (mmHg) Standard Deviation 9.84
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 6, post-oxaliplatin	77.9 Millimeters of mercury (mmHg) Standard Deviation 8.28	77.6 Millimeters of mercury (mmHg) Standard Deviation 9.01
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) DBP: Cycle 6, End of cycle	77.9 Millimeters of mercury (mmHg) Standard Deviation 8.36	77.5 Millimeters of mercury (mmHg) Standard Deviation 8.83
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 1, post-oxaliplatin	130.6 Millimeters of mercury (mmHg) Standard Deviation 15.61	126.8 Millimeters of mercury (mmHg) Standard Deviation 14.11
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 1, End of cycle	128.7 Millimeters of mercury (mmHg) Standard Deviation 16.49	126.7 Millimeters of mercury (mmHg) Standard Deviation 15.04
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 2, post-oxaliplatin	130.1 Millimeters of mercury (mmHg) Standard Deviation 15.94	129.3 Millimeters of mercury (mmHg) Standard Deviation 15.61
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 2, End of cycle	128.9 Millimeters of mercury (mmHg) Standard Deviation 14.93	127.8 Millimeters of mercury (mmHg) Standard Deviation 15.30
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 3, post-oxaliplatin	131.0 Millimeters of mercury (mmHg) Standard Deviation 17.00	128.7 Millimeters of mercury (mmHg) Standard Deviation 15.57
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 3, End of cycle	128.8 Millimeters of mercury (mmHg) Standard Deviation 15.17	127.7 Millimeters of mercury (mmHg) Standard Deviation 15.58
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 4, post-oxaliplatin	131.8 Millimeters of mercury (mmHg) Standard Deviation 16.37	129.0 Millimeters of mercury (mmHg) Standard Deviation 15.96
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 4, End of cycle	128.0 Millimeters of mercury (mmHg) Standard Deviation 14.06	128.3 Millimeters of mercury (mmHg) Standard Deviation 15.39
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 5, post-oxaliplatin	131.3 Millimeters of mercury (mmHg) Standard Deviation 16.53	129.7 Millimeters of mercury (mmHg) Standard Deviation 16.01
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 5, End of cycle	128.6 Millimeters of mercury (mmHg) Standard Deviation 15.43	128.8 Millimeters of mercury (mmHg) Standard Deviation 15.82
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 6, post-oxaliplatin	132.2 Millimeters of mercury (mmHg) Standard Deviation 15.61	131.5 Millimeters of mercury (mmHg) Standard Deviation 17.07
Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) SBP: Cycle 6, End of cycle	129.7 Millimeters of mercury (mmHg) Standard Deviation 14.65	129.1 Millimeters of mercury (mmHg) Standard Deviation 15.04

Measure	Placebo n=352 participants at risk Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 participants at risk Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Gastrointestinal disorders Diarrhoea	0.85% 3/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.85% 3/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Intestinal obstruction	0.57% 2/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Ileus	0.57% 2/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Abdominal pain	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Rectal haemorrhage	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Constipation	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Gastritis	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Deep vein thrombosis	0.57% 2/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Thrombosis	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Hypertensive crisis	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Hypotension	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Hypovolaemic shock	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Orthostatic hypotension	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Venous thrombosis	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Angina unstable	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Angina pectoris	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Atrial fibrillation	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Atrioventricular block complete	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Cardiac failure	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Cardiopulmonary failure	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Cardiovascular disorder	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Cardiac disorders Tachycardia	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Infections and infestations Pneumonia	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Infections and infestations Infection	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Infections and infestations Bronchitis	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Infections and infestations Catheter related infection	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Infections and infestations Febrile infection	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.57% 2/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.85% 3/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Blood and lymphatic system disorders Neutropenia	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
General disorders Pyrexia	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.56% 2/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
General disorders Sudden death	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Nervous system disorders Cerebral ischaemia	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Nervous system disorders Transient ischaemic attack	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Metabolism and nutrition disorders Dehydration	0.28% 1/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.00% 0/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour compression	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Renal and urinary disorders Ureteric stenosis	0.00% 0/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	0.28% 1/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.

Measure	Placebo n=352 participants at risk Eligible participants received placebo to match casopitant, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.	Casopitant 90 mg n=355 participants at risk Eligible participants received casopitant 90 mg, via IV route, (along with Ondansetron 8 mg BID orally and dexamethasone 8 mg IV) on Day 1 of each cycle over 30 minutes.
Gastrointestinal disorders Diarrhoea	21.0% 74/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	27.0% 96/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Nausea	21.0% 74/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	24.8% 88/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Constipation	11.1% 39/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	10.7% 38/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Vomiting	9.9% 35/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	4.5% 16/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Stomatitis	6.2% 22/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	5.9% 21/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Dyspepsia	5.4% 19/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	5.9% 21/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Gastrointestinal disorders Abdominal pain	6.2% 22/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	3.7% 13/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Blood and lymphatic system disorders Neutropenia	26.7% 94/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	30.4% 108/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Blood and lymphatic system disorders Thrombocytopenia	7.1% 25/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	10.7% 38/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Blood and lymphatic system disorders Anaemia	7.4% 26/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	3.9% 14/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Blood and lymphatic system disorders Leukopenia	6.5% 23/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	3.9% 14/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Nervous system disorders Peripheral sensory neuropathy	9.4% 33/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	13.0% 46/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Nervous system disorders Paraesthesia	10.2% 36/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	6.8% 24/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Nervous system disorders Neuropathy peripheral	8.2% 29/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	8.5% 30/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Nervous system disorders Headache	5.1% 18/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	7.3% 26/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
General disorders Fatigue	15.9% 56/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	14.9% 53/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Metabolism and nutrition disorders Anorexia	8.5% 30/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	6.8% 24/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.
Vascular disorders Hypertension	4.3% 15/352 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.	5.4% 19/355 • Up to 35 days. SAE and non-SAE were collected and are reported for the Safety Population.