Trial Outcomes & Findings for A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma (NCT NCT01170663)

NCT ID: NCT01170663

Last Updated: 2019-09-18

Results Overview

OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 665 participants
• Primary outcome timeframe: Randomization up to 27.5 months
• Results posted on: 2019-09-18

Participant Flow

Completers include participants that discontinued study drugs either due to progressive disease (PD), due to an adverse event or died due to any cause, but not necessarily had any survival-FU assessment done.

Participant milestones

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel 8 milligrams/kilogram (mg/kg) of ramucirumab (IMC-1121B) was administered by intravenous (IV) infusion on Days 1 and 15 in combination with 80 milligrams/square meter (mg/m²) paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Study STARTED	330	335
Overall Study Received Any Treatment (Safety Pop)	327	329
Overall Study COMPLETED	316	315
Overall Study NOT COMPLETED	14	20

Reasons for withdrawal

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel 8 milligrams/kilogram (mg/kg) of ramucirumab (IMC-1121B) was administered by intravenous (IV) infusion on Days 1 and 15 in combination with 80 milligrams/square meter (mg/m²) paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Study Lost to Follow-up	3	9
Overall Study Withdrawal of consent without follow-up	11	11

Baseline Characteristics

A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma

Baseline characteristics by cohort

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=330 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=335 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.	Total n=665 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	205 Participants n=5 Participants	213 Participants n=7 Participants	418 Participants n=5 Participants
Age, Categorical >=65 years	125 Participants n=5 Participants	122 Participants n=7 Participants	247 Participants n=5 Participants
Age, Continuous	61 years n=5 Participants	61 years n=7 Participants	61 years n=5 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	92 Participants n=7 Participants	193 Participants n=5 Participants
Sex: Female, Male Male	229 Participants n=5 Participants	243 Participants n=7 Participants	472 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants	26 Participants n=7 Participants	57 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	299 Participants n=5 Participants	309 Participants n=7 Participants	608 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	110 Participants n=5 Participants	121 Participants n=7 Participants	231 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized White	208 Participants n=5 Participants	199 Participants n=7 Participants	407 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Portugal	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Estonia	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Taiwan	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Spain	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Russia	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Chile	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Italy	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment France	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Region of Enrollment Australia	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Region of Enrollment South Korea	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment Lithuania	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Austria	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United Kingdom	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Hungary	20 Participants n=5 Participants	9 Participants n=7 Participants	29 Participants n=5 Participants
Region of Enrollment Mexico	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Argentina	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Poland	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Region of Enrollment Brazil	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment Belgium	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment Singapore	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Romania	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Bulgaria	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Germany	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Region of Enrollment Japan	68 Participants n=5 Participants	72 Participants n=7 Participants	140 Participants n=5 Participants
Region of Enrollment Hong Kong	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Israel	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization up to 27.5 months

Population: All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =74, Placebo plus Paclitaxel =75.

OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=330 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=335 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Overall Survival Time (OS)	9.6 months Interval 8.5 to 10.8	7.4 months Interval 6.3 to 8.4

SECONDARY outcome

Timeframe: Randomization up to 22.2 months

Population: All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =51, Placebo plus Paclitaxel =39.

PFS was measured from date of randomization to first radiographically documented progressive disease (PD) or death due to any cause. PD defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Participants who had no baseline or post baseline radiological tumor assessment were censored at date of randomization. Participants who had no tumor progression or death within 2 scan intervals following the last assessment were censored at the date of last radiographic tumor assessment. Participants who began new anticancer treatment and had no tumor progression were censored at date of assessment prior to initiation of new therapy. Participants lost to follow-up or withdrew consent were censored at the date of their last assessment.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=330 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=335 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Progression-Free Survival (PFS)	4.4 months Interval 4.2 to 5.3	2.9 months Interval 2.8 to 3.0

SECONDARY outcome

Timeframe: Baseline up to 22.2 months

Population: All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =107, Placebo plus Paclitaxel =94.

TTP was defined as the time from randomization until date of radiographic progression using RECIST v1.1 criteria. PD was defined as having a ≥20% increase in sum of longest diameter (LD) of target lesions and at minimum 5 millimeters (mm) increase above nadir. Participants who did not progress or were lost to follow-up were censored at the date of last tumor assessment. Participants who had no baseline tumor assessment or no post baseline assessment and no death reported with 2 scan intervals post randomization were censored at date of randomization. Participants with no progression and not died within 2 scan intervals after last assessment were censored at date of last tumor assessment. Participants with no post baseline assessment or tumor progression but death reported within 2 scan intervals after randomization were censored at date of death.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=330 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=335 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Time to Progressive Disease (TTP)	5.52 months Interval 4.5 to 5.68	3.02 months Interval 2.86 to 4.14

SECONDARY outcome

Timeframe: Randomization up to 22.2 months

Population: All participants according to the treatment group to which they were randomized.

BOR was defined as the best response across all time points from randomization until radiologically confirmed PD using RECIST, v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. PD was defined as having a ≥20% increase in sum of LD of target lesions and ≥5 mm increase above nadir. SD was defined as small changes that did not meet above criteria.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=330 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=335 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD PR	27.3 percentage of participants	15.8 percentage of participants
Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD PD	13.0 percentage of participants	24.8 percentage of participants
Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD Not Evaluable	0.3 percentage of participants	0.9 percentage of participants
Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD CR	0.6 percentage of participants	0.3 percentage of participants
Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD SD	52.1 percentage of participants	47.5 percentage of participants
Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD No Tumor Response Evaluation	6.7 percentage of participants	10.7 percentage of participants

SECONDARY outcome

Timeframe: Randomization up to 22.2 months

Population: All participants according to the treatment group to which they were randomized.

ORR was the percentage of participants who had CR or PR defined using RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. Percentage of participants calculated as: (number of participants with CR + PR)/(total number of participants)*100.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=330 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=335 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Percentage of Participants With CR or PR (Objective Response Rate [ORR])	27.9 percentage of participants Interval 23.3 to 33.0	16.1 percentage of participants Interval 12.6 to 20.4

SECONDARY outcome

Timeframe: Prior to and after ramucirumab (IMC-1121B) infusion: Day 1 Cycles 1, 2 and 3 (28-day cycles) Doses 1, 4, 7 and 30-37 days after last dose of study therapy up to 103 weeks

Population: All participants according to the treatment group to which they were randomized and received at least 1 dose of study drug with anti-ramucirumab antibodies.

Participants who developed treatment-emergent antibody responses to Ramucirumab (IMC-1121B) after baseline.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=320 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=323 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Percentage of Participants With Anti-Ramucirumab Antibodies (Serum Anti-Ramucirumab Antibody Assessment )(Immunogenicity)	1.6 percentage of participants	0.3 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1, Day 1, 1 hour post end of infusion (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=259 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Maximum Concentration (Cmax) After First Ramucirumab (IMC-1211B) Infusion	146 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 28	—

SECONDARY outcome

Timeframe: Cycle 2, Day 15 1 hour post end of infusion (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=200 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Cmax After 4th Ramucirumab (IMC-1211B) Infusion	193 µg/mL Geometric Coefficient of Variation 34	—

SECONDARY outcome

Timeframe: Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=127 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Cmax After 7th Ramucirumab (IMC-1211B) Infusion	216 µg/mL Geometric Coefficient of Variation 30	—

SECONDARY outcome

Timeframe: Cycle 1, Day 1 predose (28-day cycles)

Population: Zero participants were analyzed.

This outcome measure was included in error as the time point was before ramucirumab (IMC-1211B) was administered. Cmin was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 2, Day 15 (28-day cycle)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmin observations at specific timepoint.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=203 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Cmin Prior to 4th Ramucirumab (IMC-1211B) Infusion	45.0 µg/mL Geometric Coefficient of Variation 50	—

SECONDARY outcome

Timeframe: Cycle 4, Day 1 (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmin observations at specific timepoint.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=142 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Cmin Prior to 7th Ramucirumab (IMC-1211B) Infusion	62.8 µg/mL Geometric Coefficient of Variation 47	—

SECONDARY outcome

Timeframe: Baseline, end of therapy (up to 103 weeks)

Population: All participants according to the treatment group to which they were randomized with baseline and end of treatment Global Health Status observations.

EORTC QLQ-C30 v3.0 is a 30-item, self-administered questionnaire with multidimensional scales assessing 15 domains (5 functional domains [physical, role, cognitive, emotional, and social], 9 symptom scales [fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties] and global health status scale). 28 questions assessed on a 1 (not at all) to 4 (very much) scale and the remaining 2 questions used a 1 (poor) to 7 (excellent) scale. A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=209 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=202 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Change From Baseline to End of Therapy in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life: Questionnaire (QLQ-C30) in Global Health Status	-13.5 units on a scale Standard Deviation 23.24	-12.1 units on a scale Standard Deviation 24.81

SECONDARY outcome

Timeframe: Baseline, end of therapy (up to 103 weeks)

Population: All participants according to the treatment group to which they were randomized with baseline and end of treatment EQ-5D observations.

The EQ-5D is a generic, multidimensional, health status instrument. The profile allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale [1 (no problem), 2 (some problems), and 3 (major problems)]. These combinations of responses were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=205 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=201 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Change From Baseline to End of Therapy in European Quality of Life Questionnaire-5 Dimension (EuroQol EQ-5D) Index Score	-0.16 units on a scale Standard Deviation 0.279	-0.19 units on a scale Standard Deviation 0.337

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 103 weeks and within 30 days of last dose of study drug

Population: All randomized participants who received at least 1 dose of study drug and based on the treatment each participant received.

Participants who died or who had clinically significant events defined as serious AEs (SAEs) and other non-serious AEs (regardless of causality). A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Measure	Ramucirumab (IMC-1211B) Plus Paclitaxel n=327 Participants 8 mg/kg of ramucirumab (IMC-1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² paclitaxel administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo Plus Paclitaxel n=329 Participants Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered on Days 1, 8, and 15 of a 28-day cycle.
Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died Other Non-serious AEs	324 participants	321 participants
Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died SAEs	161 participants	146 participants
Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died Died	37 participants	52 participants

Adverse Events

Ramucirumab and Paclitaxel

Serious events: 161 serious events

Other events: 324 other events

Deaths: 0 deaths

Placebo and Paclitaxel

Serious events: 146 serious events

Other events: 321 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ramucirumab and Paclitaxel n=327 participants at risk 8 mg/kg ramucirumab (IMC1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo and Paclitaxel n=329 participants at risk Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² administered on Days 1, 8, and 15 of a 28-day cycle.
Gastrointestinal disorders Abdominal pain upper	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Anal haemorrhage	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Anaemia	2.4% 8/327 • Number of events 8 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	2.1% 7/329 • Number of events 10 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Febrile neutropenia	2.4% 8/327 • Number of events 8 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.5% 5/329 • Number of events 6 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Leukopenia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Neutropenia	3.7% 12/327 • Number of events 17 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.2% 4/329 • Number of events 4 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Acute coronary syndrome	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Angina pectoris	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Atrial fibrillation	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Atrial flutter	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Atrial thrombosis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Cardiac failure	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Extrasystoles	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Cardiac disorders Myocardial infarction	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Congenital, familial and genetic disorders Pyloric stenosis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Ear and labyrinth disorders Hearing impaired	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Ear and labyrinth disorders Vertigo	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Eye disorders Cataract	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Eye disorders Lacrimation increased	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Abdominal pain	3.1% 10/327 • Number of events 12 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	3.3% 11/329 • Number of events 12 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Aphagia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Ascites	1.5% 5/327 • Number of events 8 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.91% 3/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Constipation	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Diarrhoea	1.5% 5/327 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Diverticular perforation	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Dysphagia	1.2% 4/327 • Number of events 4 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.91% 3/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Gastric haemorrhage	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 4/327 • Number of events 4 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Gastrointestinal obstruction	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Gastrointestinal perforation	0.61% 2/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Haematemesis	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Ileus	0.61% 2/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Ileus paralytic	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Intestinal obstruction	1.8% 6/327 • Number of events 6 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.91% 3/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Intestinal perforation	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Malabsorption	0.31% 1/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Melaena	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Mouth ulceration	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Nausea	0.61% 2/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.5% 5/329 • Number of events 6 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Obstruction gastric	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Odynophagia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophageal food impaction	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophageal haemorrhage	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophageal perforation	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophageal spasm	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Oesophagitis	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Pancreatitis acute	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Peritonitis	1.5% 5/327 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Pneumatosis intestinalis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Small intestinal obstruction	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.2% 4/329 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Small intestinal stenosis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Subileus	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Vomiting	2.1% 7/327 • Number of events 9 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	3.0% 10/329 • Number of events 11 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Asthenia	1.5% 5/327 • Number of events 7 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Chest pain	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Death	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Device dislocation	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Disease progression	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Drowning	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Fatigue	1.5% 5/327 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	2.1% 7/329 • Number of events 9 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Feeling abnormal	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders General physical health deterioration	2.4% 8/327 • Number of events 10 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	2.7% 9/329 • Number of events 12 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Injection site injury	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Multi-organ failure	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Oedema peripheral	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Pain	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Pyrexia	2.4% 8/327 • Number of events 9 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	2.1% 7/329 • Number of events 9 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Hepatobiliary disorders Bile duct obstruction	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Hepatobiliary disorders Cholangitis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Hepatobiliary disorders Cholecystitis	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Hepatobiliary disorders Cholecystitis acute	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Hepatobiliary disorders Jaundice	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Anal abscess	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Appendicitis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Bacteraemia	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Biliary sepsis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Biliary tract infection	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Bronchopneumonia	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Cellulitis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Device related infection	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.91% 3/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Device related sepsis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Diarrhoea infectious	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Endocarditis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Herpes zoster	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Influenza	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Lobar pneumonia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Localised infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Lower respiratory tract infection	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Lung infection	0.92% 3/327 • Number of events 6 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Neutropenic sepsis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Perirectal abscess	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Peritonitis bacterial	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Pneumonia	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.91% 3/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Pseudomonas infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Pulmonary sepsis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Respiratory tract infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Sepsis	1.5% 5/327 • Number of events 7 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.2% 4/329 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Septic shock	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Staphylococcal infection	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Staphylococcal sepsis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Urinary tract infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Urinary tract infection bacterial	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Urosepsis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Viral infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Wound infection	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Injury, poisoning and procedural complications Clavicle fracture	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Injury, poisoning and procedural complications Gastroenteritis radiation	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Injury, poisoning and procedural complications Incisional hernia	0.31% 1/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Injury, poisoning and procedural complications Splenic rupture	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Alanine aminotransferase increased	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Anticoagulation drug level above therapeutic	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Aspartate aminotransferase increased	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Blood creatinine increased	0.31% 1/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Blood urea increased	0.31% 1/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Gamma-glutamyltransferase increased	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Cachexia	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Decreased appetite	0.61% 2/327 • Number of events 4 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.5% 5/329 • Number of events 6 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Dehydration	1.8% 6/327 • Number of events 7 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.8% 6/329 • Number of events 7 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Hypercalcaemia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Hyponatraemia	0.92% 3/327 • Number of events 4 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Hypophagia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Arthralgia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Back pain	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain cancer metastatic	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant ascites	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	14.7% 48/327 • Number of events 65 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	14.9% 49/329 • Number of events 66 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Akathisia	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Cerebral haemorrhage	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Cerebral infarction	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Cerebrovascular accident	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Coma	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Hydrocephalus	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Intracranial pressure increased	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Ischaemic stroke	0.31% 1/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Spinal cord compression	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Azotaemia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Dysuria	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Hydronephrosis	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Obstructive uropathy	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Renal failure	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Renal failure acute	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Urinary retention	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Reproductive system and breast disorders Gynaecomastia	0.44% 1/226 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/237 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.92% 3/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.2% 4/329 • Number of events 4 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.91% 3/329 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.5% 5/327 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.2% 4/329 • Number of events 5 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.61% 2/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	1.8% 6/329 • Number of events 8 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Arteriosclerosis	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Deep vein thrombosis	0.61% 2/327 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Hypotension	0.61% 2/327 • Number of events 3 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Hypovolaemic shock	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Vein disorder	0.31% 1/327 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.00% 0/329 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Vena cava thrombosis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.30% 1/329 • Number of events 1 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Venous thrombosis	0.00% 0/327 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	0.61% 2/329 • Number of events 2 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).

Other adverse events

Measure	Ramucirumab and Paclitaxel n=327 participants at risk 8 mg/kg ramucirumab (IMC1121B) was administered by IV infusion on Days 1 and 15 in combination with 80 mg/m² administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle.	Placebo and Paclitaxel n=329 participants at risk Placebo was administered by IV infusion on Days 1 and 15, in combination with 80 mg/m² administered on Days 1, 8, and 15 of a 28-day cycle.
Blood and lymphatic system disorders Anaemia	33.6% 110/327 • Number of events 261 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	35.3% 116/329 • Number of events 274 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Leukopenia	33.9% 111/327 • Number of events 471 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	21.0% 69/329 • Number of events 199 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Neutropenia	53.2% 174/327 • Number of events 878 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	31.0% 102/329 • Number of events 247 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Blood and lymphatic system disorders Thrombocytopenia	13.1% 43/327 • Number of events 103 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.1% 20/329 • Number of events 37 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Abdominal distension	6.1% 20/327 • Number of events 27 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.1% 20/329 • Number of events 25 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Abdominal pain	30.0% 98/327 • Number of events 165 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	18.8% 62/329 • Number of events 104 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Abdominal pain upper	9.5% 31/327 • Number of events 48 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	10.6% 35/329 • Number of events 52 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Ascites	9.5% 31/327 • Number of events 46 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.6% 25/329 • Number of events 39 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Constipation	21.4% 70/327 • Number of events 95 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	21.6% 71/329 • Number of events 89 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Diarrhoea	32.1% 105/327 • Number of events 250 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	23.1% 76/329 • Number of events 126 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Dysphagia	5.2% 17/327 • Number of events 25 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	5.2% 17/329 • Number of events 18 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Nausea	34.9% 114/327 • Number of events 236 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	32.2% 106/329 • Number of events 183 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Stomatitis	19.6% 64/327 • Number of events 103 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.3% 24/329 • Number of events 33 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Gastrointestinal disorders Vomiting	26.0% 85/327 • Number of events 142 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	19.8% 65/329 • Number of events 111 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Asthenia	20.8% 68/327 • Number of events 179 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	13.7% 45/329 • Number of events 73 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Fatigue	39.1% 128/327 • Number of events 281 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	31.6% 104/329 • Number of events 209 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Oedema peripheral	25.1% 82/327 • Number of events 122 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	13.7% 45/329 • Number of events 57 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
General disorders Pyrexia	17.1% 56/327 • Number of events 83 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	10.6% 35/329 • Number of events 53 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Nasopharyngitis	7.0% 23/327 • Number of events 34 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	5.8% 19/329 • Number of events 24 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Infections and infestations Urinary tract infection	5.5% 18/327 • Number of events 22 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	3.3% 11/329 • Number of events 11 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Alanine aminotransferase increased	6.1% 20/327 • Number of events 43 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	5.5% 18/329 • Number of events 22 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Aspartate aminotransferase increased	8.3% 27/327 • Number of events 62 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	5.2% 17/329 • Number of events 23 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Investigations Weight decreased	13.8% 45/327 • Number of events 79 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	14.9% 49/329 • Number of events 68 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Decreased appetite	40.1% 131/327 • Number of events 225 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	31.9% 105/329 • Number of events 172 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Hypoalbuminaemia	9.5% 31/327 • Number of events 47 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	4.0% 13/329 • Number of events 16 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Metabolism and nutrition disorders Hyponatraemia	5.2% 17/327 • Number of events 23 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	2.7% 9/329 • Number of events 13 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Arthralgia	8.9% 29/327 • Number of events 54 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.1% 20/329 • Number of events 25 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Back pain	11.6% 38/327 • Number of events 48 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	11.9% 39/329 • Number of events 47 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Myalgia	10.4% 34/327 • Number of events 62 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	9.7% 32/329 • Number of events 44 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Musculoskeletal and connective tissue disorders Pain in extremity	5.8% 19/327 • Number of events 21 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	3.0% 10/329 • Number of events 10 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	5.2% 17/327 • Number of events 17 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.9% 26/329 • Number of events 26 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Dizziness	6.1% 20/327 • Number of events 25 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	4.0% 13/329 • Number of events 16 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Dysgeusia	8.9% 29/327 • Number of events 32 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.4% 21/329 • Number of events 23 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Headache	9.8% 32/327 • Number of events 50 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.7% 22/329 • Number of events 37 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Neuropathy peripheral	14.4% 47/327 • Number of events 88 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	9.1% 30/329 • Number of events 51 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Paraesthesia	7.3% 24/327 • Number of events 41 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.6% 25/329 • Number of events 41 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Peripheral sensory neuropathy	17.4% 57/327 • Number of events 122 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	10.9% 36/329 • Number of events 63 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Nervous system disorders Polyneuropathy	5.5% 18/327 • Number of events 31 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.7% 22/329 • Number of events 38 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Psychiatric disorders Insomnia	9.5% 31/327 • Number of events 32 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.9% 26/329 • Number of events 27 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Renal and urinary disorders Proteinuria	16.8% 55/327 • Number of events 156 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	6.1% 20/329 • Number of events 34 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Cough	12.5% 41/327 • Number of events 46 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.9% 26/329 • Number of events 35 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Dysphonia	5.2% 17/327 • Number of events 22 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	2.7% 9/329 • Number of events 13 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.5% 41/327 • Number of events 61 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	9.4% 31/329 • Number of events 38 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Respiratory, thoracic and mediastinal disorders Epistaxis	30.6% 100/327 • Number of events 157 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.0% 23/329 • Number of events 34 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Skin and subcutaneous tissue disorders Alopecia	32.7% 107/327 • Number of events 137 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	38.6% 127/329 • Number of events 159 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Skin and subcutaneous tissue disorders Dry skin	7.6% 25/327 • Number of events 28 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	3.0% 10/329 • Number of events 10 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Skin and subcutaneous tissue disorders Pruritus	6.1% 20/327 • Number of events 23 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	3.3% 11/329 • Number of events 13 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Skin and subcutaneous tissue disorders Rash	10.7% 35/327 • Number of events 44 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	7.6% 25/329 • Number of events 28 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).
Vascular disorders Hypertension	23.9% 78/327 • Number of events 155 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).	4.9% 16/329 • Number of events 25 One (1) participant was randomized to the placebo group but received ramucirumab in error. This participant was included in the ramucirumab group in the Safety population (as treated).

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
• Publication restrictions are in place

Restriction type: OTHER