Trial Outcomes & Findings for A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer (NCT NCT02314117)

Last Updated: 2021-08-26

Results Overview

PFS time was measured from the date of randomization to the date of radiographic(rgr) documentation of progression(by RECIST v.1.1) or the date of death due to any cause, whichever was earlier.If a participant did not have a complete baseline tumor assessment,then the PFS time was censored at the randomization date.If a participant was not known to have died or have rgr documented progression as of the data cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. If death or progressive disease(PD) occurred after 2 or more consecutive missing rgr visits,censoring occurred at the date of the last rgr visit prior to the missed visits.If death or PD occurred after postdiscontinuation(pdis) systemic anticancer therapy,censoring occurred at the date of last rgr visit prior to the start of pdis systemic anticancer therapy. PD was defined according to RECIST v.1.1.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

645 participants

Primary outcome timeframe

Randomization to Radiological Disease Progression or Death from Any Cause (Up to 26 Months)

Results posted on

2021-08-26

Participant Flow

Completers are defined as participants who died or those who were alive and off treatment when the study completed.

Participant milestones

Participant milestones
Measure	Ramucirumab + Cisplatin + Capecitabine 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Overall Study STARTED	326	319
Overall Study Received at Least One Dose of Study Drug	323	315
Overall Study COMPLETED	314	303
Overall Study NOT COMPLETED	12	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Ramucirumab + Cisplatin + Capecitabine 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Overall Study Lost to Follow-up	9	14
Overall Study Withdrawal by Subject	3	2

Baseline Characteristics

A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.	Total n=645 Participants Total of all reporting groups
Race (NIH/OMB) White	256 Participants n=5 Participants	264 Participants n=7 Participants	520 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) Asian	38 Participants n=5 Participants	31 Participants n=7 Participants	69 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Age, Continuous	58.9 years STANDARD_DEVIATION 11.6 • n=5 Participants	60.1 years STANDARD_DEVIATION 11.8 • n=7 Participants	59.5 years STANDARD_DEVIATION 11.7 • n=5 Participants
Sex: Female, Male Female	112 Participants n=5 Participants	104 Participants n=7 Participants	216 Participants n=5 Participants
Sex: Female, Male Male	214 Participants n=5 Participants	215 Participants n=7 Participants	429 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	67 Participants n=5 Participants	62 Participants n=7 Participants	129 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	227 Participants n=5 Participants	245 Participants n=7 Participants	472 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	32 Participants n=5 Participants	12 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment Puerto Rico	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Argentina	21 Participants n=5 Participants	22 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment Hungary	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment United States	42 Participants n=5 Participants	31 Participants n=7 Participants	73 Participants n=5 Participants
Region of Enrollment Czechia	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment Japan	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Region of Enrollment United Kingdom	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Region of Enrollment Russia	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment Spain	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment Canada	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Netherlands	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Belgium	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Finland	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Denmark	12 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Poland	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment Italy	28 Participants n=5 Participants	45 Participants n=7 Participants	73 Participants n=5 Participants
Region of Enrollment Mexico	26 Participants n=5 Participants	26 Participants n=7 Participants	52 Participants n=5 Participants
Region of Enrollment Israel	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Region of Enrollment France	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Region of Enrollment Germany	20 Participants n=5 Participants	13 Participants n=7 Participants	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to Radiological Disease Progression or Death from Any Cause (Up to 26 Months)

Population: First 508 randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=87 and Placebo + Cisplatin + Capecitabine=62.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=255 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=253 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Progression-free Survival (PFS)	5.72 months Interval 5.45 to 6.51	5.39 months Interval 4.47 to 5.72

SECONDARY outcome

Timeframe: Randomization to Death from Any Cause (Up To 30 Months)

Population: All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=87 and Placebo + Cisplatin + Capecitabine=88.

OS was time from the date of randomization to the date of death from any cause. If the participant was alive at the cutoff for analysis (or was lost to follow-up), OS data were censored for analysis on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Overall Survival (OS)	11.17 months Interval 9.92 to 11.93	10.74 months Interval 9.53 to 11.89

SECONDARY outcome

Timeframe: Randomization to Second Radiological or Symptomatic Disease Progression After the Start of Additional Systemic Anticancer Treatment or Death from Any Cause (Up To 26 Months)

Population: All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=74 and Placebo + Cisplatin + Capecitabine=74.

PFS2 was defined as the time from the date of randomization to second disease progression (defined as objective radiological or symptomatic progression), or death of any cause, whichever occurs first. Participants alive and for whom a second disease progression has not been observed (including participants who did not receive any additional systemic anticancer treatments) were censored at the last time known to be alive and without second disease progression. The second progression refers to disease progression on or after additional systemic anticancer therapy, regardless if any earlier progression is observed or not(e.g. at the end of study treatment). It is assessed by investigator based on overall clinical evaluation, not limited to RECIST.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Progression- Free Survival 2 (PFS2)	10.18 months Interval 9.03 to 10.84	9.20 months Interval 8.34 to 9.99

SECONDARY outcome

Timeframe: Randomization to Disease Progression (Up To 26 Months)

Population: All randomized participants.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1).Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).ORR calculated as:(sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])	41.1 percentage of participants Interval 35.8 to 46.4	36.4 percentage of participants Interval 31.1 to 41.6

SECONDARY outcome

Timeframe: Randomization to Disease Progression (Up To 26 Months)

Population: All randomized participants.

DCR was the percentage of participants with a best overall response of CR, PR, or SD as per Response using RECIST v1.1 criteria. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])	81.9 percentage of participants Interval 77.7 to 86.1	76.5 percentage of participants Interval 71.8 to 81.1

SECONDARY outcome

Timeframe: Randomization to Disease Progression (Up To 24 Months)

Population: All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=149 and Placebo + Cisplatin + Capecitabine=111.

TTP was time from the date of randomization to the date of radiographic progression (according to RECIST v.1.1). If a participant died due to any reason without radiographic progression, TTP is censored at the last adequate tumor assessment. Target lesions: Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions: PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Time to Progression (TTP)	6.77 months Interval 5.88 to 7.66	5.78 months Interval 5.55 to 6.37

SECONDARY outcome

Timeframe: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months)

Population: All randomized participants. Participants censored : Ramucirumab + Cisplatin + Capecitabine= 23 and Placebo + Cisplatin + Capecitabine=10.

Participants achieved an objective response if they had a best overall response of CR or PR.Target lesions- CR:Disappearance of all lesions;any pathological lymph nodes must have reduction in short axis to \<10 mm.PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum.PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study(the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s).Non target lesions - CR: Disappearance of all lesions and normalization of tumour marker levels;all lymph nodes must be non-pathological in size. Non-CR/Non-PD:Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels.PD:Unequivocal progression of existing lesions or the appearance of new lesion(s).If a participant was not known to have died or have radiographically documented PD as of the data inclusion cutoff date,DOR was censored at the date of the last adequate tumor assessment.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=134 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=116 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Duration of Response (DoR)	5.72 months Interval 5.09 to 6.34	4.27 months Interval 3.88 to 4.9

SECONDARY outcome

Timeframe: Randomization, First worsening in QoL (Up To 26 Months)

Population: All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=215 and Placebo + Cisplatin + Capecitabine=217

Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale	9.00 months Interval 8.08 to 12.58	9.46 months Interval 6.74 to 11.99

SECONDARY outcome

Timeframe: Randomization, 30 Days After Treatment Discontinuation (Up To 5 Months)

Population: All randomized participants who provided data at baseline and cycle 6.

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=136 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=125 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Change in Health Status on the EuroQol 5-Dimensions 5-Level Instrument (EQ-5D- 5L) EQ-5D index	-0.008 units on a scale Standard Deviation 0.148	-0.010 units on a scale Standard Deviation 0.157
Change in Health Status on the EuroQol 5-Dimensions 5-Level Instrument (EQ-5D- 5L) EQ-5D VAS	0.8 units on a scale Standard Deviation 18.56	1.5 units on a scale Standard Deviation 20.33

SECONDARY outcome

Timeframe: Randomization to ECOG PS ≥2 (Up To 26 Months)

Population: All randomized participants. Participants censored: Ramucirumab + Cisplatin + Capecitabine=254 and Placebo + Cisplatin + Capecitabine= 260.

The time from the date of randomization to the first date observing ECOG PS ≥2 (that is, deterioration from baseline status of 0 or 1). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. ECOG Performance Status: 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled. Cannot carry on any selfcare.Totally confined to bed or chair,5- Dead.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=326 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=319 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	NA months Interval 12.2 to Very few events occurred therefore data were not assessable.	NA months Very few events occurred therefore data were not assessable.

SECONDARY outcome

Timeframe: Predose Cycle 1 through 30 Days After Treatment Discontinuation (Up To 24 Months)

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

Participants who developed treatment-emergent antibody responses to Ramucirumab postbaseline.

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=323 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine n=315 Participants Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Number of Participants With Anti-Ramucirumab Antibodies	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI

Population: All randomized participants who received ramucirumab and had evaluable PK data.

Pharmacokinetics (PK): Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=283 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab Cycle 1, Day 1	133 Microgram/milliliter (µg/mL) Geometric Coefficient of Variation 31	—
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab Cycle 3, Day 1	173 Microgram/milliliter (µg/mL) Geometric Coefficient of Variation 35	—
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab Cycle 9, Day 1	169 Microgram/milliliter (µg/mL) Geometric Coefficient of Variation 60	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI

Population: All randomized participants who received ramucirumab and had evaluable PK data

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Outcome measures

Outcome measures
Measure	Ramucirumab + Cisplatin + Capecitabine n=268 Participants 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo + Cisplatin + Capecitabine Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
PK: Minimum Concentration (Cmin) of Ramucirumab Cycle 1, Day 8	40.7 µg/mL Geometric Coefficient of Variation 35	—
PK: Minimum Concentration (Cmin) of Ramucirumab Cycle 2, Day 1	35.7 µg/mL Geometric Coefficient of Variation 56	—
PK: Minimum Concentration (Cmin) of Ramucirumab Cycle 3, Day 1	51.2 µg/mL Geometric Coefficient of Variation 47	—
PK: Minimum Concentration (Cmin) of Ramucirumab Cycle 5, Day 1	69.7 µg/mL Geometric Coefficient of Variation 52	—
PK: Minimum Concentration (Cmin) of Ramucirumab Cycle 9, Day 1	77.6 µg/mL Geometric Coefficient of Variation 98	—

Adverse Events

LY3009806+Capecitabine+Cisplatin

Serious events: 161 serious events

Other events: 315 other events

Deaths: 0 deaths

Placebo+Capecitabine+Cisplatin

Serious events: 150 serious events

Other events: 304 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	LY3009806+Capecitabine+Cisplatin n=323 participants at risk 8 milligrams/kilogram (mg/kg) ramucirumab given intravenously (IV) on days 1 and 8 in combination with 80 mg/square meter (m\^2) cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day fluorouracil (5-FU) IV on days 1 to 5 of each 21-day cycle.	Placebo+Capecitabine+Cisplatin n=315 participants at risk Placebo for blinding given IV on days 1 and 8 in combination with 80 mg/m\^2 cisplatin given IV on day 1 of each 21-day cycle (for up to 6 cycles) and 1000 mg/m\^2 capecitabine given orally twice a day on days 1 through 14. Participants that were unable to take capecitabine will be given 800 mg/m\^2/day 5-FU IV on days 1 to 5 of each 21-day cycle.
Blood and lymphatic system disorders Anaemia	32.2% 104/323 • Number of events 276 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	36.2% 114/315 • Number of events 289 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	22.0% 71/323 • Number of events 218 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	23.5% 74/315 • Number of events 133 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	12.7% 41/323 • Number of events 106 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	8.3% 26/315 • Number of events 51 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Ear and labyrinth disorders Tinnitus	7.1% 23/323 • Number of events 26 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	8.6% 27/315 • Number of events 32 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	16.1% 52/323 • Number of events 80 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	16.2% 51/315 • Number of events 69 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	6.8% 22/323 • Number of events 27 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	4.8% 15/315 • Number of events 22 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	32.2% 104/323 • Number of events 161 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	24.8% 78/315 • Number of events 107 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	33.4% 108/323 • Number of events 175 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	34.0% 107/315 • Number of events 175 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	5.9% 19/323 • Number of events 20 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	3.8% 12/315 • Number of events 14 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Dysphagia	6.5% 21/323 • Number of events 33 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.4% 17/315 • Number of events 23 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	63.5% 205/323 • Number of events 459 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	59.0% 186/315 • Number of events 444 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	20.7% 67/323 • Number of events 110 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	12.4% 39/315 • Number of events 64 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	41.5% 134/323 • Number of events 249 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	37.1% 117/315 • Number of events 217 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
General disorders Asthenia	13.6% 44/323 • Number of events 133 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	12.7% 40/315 • Number of events 101 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
General disorders Fatigue	47.4% 153/323 • Number of events 316 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	46.0% 145/315 • Number of events 309 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
General disorders Mucosal inflammation	6.2% 20/323 • Number of events 31 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.4% 17/315 • Number of events 41 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
General disorders Oedema peripheral	13.9% 45/323 • Number of events 65 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	10.5% 33/315 • Number of events 46 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
General disorders Pyrexia	8.7% 28/323 • Number of events 37 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	12.7% 40/315 • Number of events 56 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	2.5% 8/323 • Number of events 11 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.4% 17/315 • Number of events 18 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	5.9% 19/323 • Number of events 29 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	3.2% 10/315 • Number of events 15 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	6.2% 20/323 • Number of events 25 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	3.8% 12/315 • Number of events 17 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	9.6% 31/323 • Number of events 60 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	8.9% 28/315 • Number of events 41 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	31.9% 103/323 • Number of events 295 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	29.2% 92/315 • Number of events 263 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations Platelet count decreased	22.3% 72/323 • Number of events 254 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	10.5% 33/315 • Number of events 75 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations Weight decreased	16.7% 54/323 • Number of events 72 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	11.7% 37/315 • Number of events 56 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Investigations White blood cell count decreased	11.5% 37/323 • Number of events 118 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	10.2% 32/315 • Number of events 109 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	40.2% 130/323 • Number of events 245 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	31.7% 100/315 • Number of events 190 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	5.9% 19/323 • Number of events 25 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	7.9% 25/315 • Number of events 30 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	5.3% 17/323 • Number of events 28 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	4.1% 13/315 • Number of events 21 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	6.2% 20/323 • Number of events 23 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	3.5% 11/315 • Number of events 21 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	11.1% 36/323 • Number of events 51 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	12.7% 40/315 • Number of events 68 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	11.1% 36/323 • Number of events 47 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	14.3% 45/315 • Number of events 97 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	5.6% 18/323 • Number of events 30 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.4% 17/315 • Number of events 21 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	8.7% 28/323 • Number of events 33 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.1% 16/315 • Number of events 20 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	11.1% 36/323 • Number of events 42 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	11.1% 35/315 • Number of events 52 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	10.5% 34/323 • Number of events 38 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	8.6% 27/315 • Number of events 31 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Nervous system disorders Headache	13.3% 43/323 • Number of events 57 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	8.6% 27/315 • Number of events 36 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	6.2% 20/323 • Number of events 30 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	2.5% 8/315 • Number of events 9 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Nervous system disorders Peripheral sensory neuropathy	12.1% 39/323 • Number of events 62 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	9.8% 31/315 • Number of events 41 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	8.4% 27/323 • Number of events 29 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	7.9% 25/315 • Number of events 27 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	19.8% 64/323 • Number of events 156 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	11.4% 36/315 • Number of events 60 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 25/323 • Number of events 29 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.7% 18/315 • Number of events 18 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 36/323 • Number of events 49 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	6.7% 21/315 • Number of events 26 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	14.9% 48/323 • Number of events 76 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	4.4% 14/315 • Number of events 19 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	11.1% 36/323 • Number of events 63 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	10.5% 33/315 • Number of events 46 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	5.9% 19/323 • Number of events 21 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.1% 16/315 • Number of events 20 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	6.2% 20/323 • Number of events 23 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.1% 16/315 • Number of events 17 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	30.7% 99/323 • Number of events 248 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	20.0% 63/315 • Number of events 121 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	5.6% 18/323 • Number of events 18 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	3.2% 10/315 • Number of events 10 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Vascular disorders Embolism venous	4.0% 13/323 • Number of events 13 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	5.4% 17/315 • Number of events 17 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.
Vascular disorders Hypertension	21.7% 70/323 • Number of events 152 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.	7.3% 23/315 • Number of events 30 • Baseline Up To 5.6 Years All participants who received at least one dose of study drug.