Trial Outcomes & Findings for A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (NCT NCT02435433)

NCT ID: NCT02435433

Last Updated: 2023-01-20

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: 399 participants
• Primary outcome timeframe: From Date of Randomization to Death from Any Cause (Up to 28 Months)
• Results posted on: 2023-01-20

Participant Flow

1. Main study: Participants who received sorafenib as first-line therapy were randomized to ramucirumab or placebo. 2. Open-Label Expansion: Participants who were not previously treated with sorafenib were enrolled into this single-arm addenda and treated with ramucirumab. The purpose of this addenda is to monitor safety, and data was reported under AE section. (Continued...)

c. China Maximized Extended Enrollment: This is an extension phase of the main study, with an additional 60 participants enrolled in China. Safety was monitored and data was reported under AE section.

Participant milestones

Measure	Ramucirumab + BSC 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Open Label Ramucirumab + BSC 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Ramucirumab MEE Cohort 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo MEE Cohort Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.
Overall Study STARTED	197	95	47	39	21
Overall Study Participants Who Received Study Drug	197	95	47	39	21
Overall Study COMPLETED	193	90	42	38	21
Overall Study NOT COMPLETED	4	5	5	1	0

Reasons for withdrawal

Measure	Ramucirumab + BSC 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Open Label Ramucirumab + BSC 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Ramucirumab MEE Cohort 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo MEE Cohort Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.
Overall Study Withdrawal by Subject	2	3	1	0	0
Overall Study Lost to Follow-up	2	2	4	1	0

Baseline Characteristics

A Study of Ramucirumab (LY3009806) Versus Placebo in Participants With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein

Baseline characteristics by cohort

Measure	Ramucirumab + BSC n=197 Participants 8 mg/kg ramucirumab administered as an IV injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + Best Supportive Care (BSC) n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.	Open Label Ramucirumab + BSC n=47 Participants 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Ramucirumab MEE Cohort n=39 Participants 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo MEE Cohort n=21 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.	Total n=399 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	64 years n=7 Participants	61 years n=5 Participants	54 years n=4 Participants	54 years n=21 Participants	62 years n=10 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	16 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	1 Participants n=21 Participants	73 Participants n=10 Participants
Sex: Female, Male Male	154 Participants n=5 Participants	79 Participants n=7 Participants	41 Participants n=5 Participants	32 Participants n=4 Participants	20 Participants n=21 Participants	326 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	22 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	129 Participants n=5 Participants	58 Participants n=7 Participants	40 Participants n=5 Participants	12 Participants n=4 Participants	9 Participants n=21 Participants	248 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	56 Participants n=5 Participants	28 Participants n=7 Participants	6 Participants n=5 Participants	27 Participants n=4 Participants	12 Participants n=21 Participants	129 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	102 Participants n=5 Participants	45 Participants n=7 Participants	26 Participants n=5 Participants	39 Participants n=4 Participants	21 Participants n=21 Participants	233 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	6 Participants n=10 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants	31 Participants n=7 Participants	13 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	104 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	34 Participants n=5 Participants	17 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	51 Participants n=10 Participants
Region of Enrollment Hong Kong	6 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	15 Participants n=10 Participants
Region of Enrollment United States	10 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	23 Participants n=10 Participants
Region of Enrollment Czechia	4 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	6 Participants n=10 Participants
Region of Enrollment Japan	41 Participants n=5 Participants	18 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	59 Participants n=10 Participants
Region of Enrollment United Kingdom	9 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	11 Participants n=10 Participants
Region of Enrollment Switzerland	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=10 Participants
Region of Enrollment Spain	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=10 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Region of Enrollment Austria	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Region of Enrollment South Korea	24 Participants n=5 Participants	14 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	38 Participants n=10 Participants
Region of Enrollment Belgium	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=10 Participants
Region of Enrollment China	3 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	39 Participants n=4 Participants	21 Participants n=21 Participants	72 Participants n=10 Participants
Region of Enrollment Taiwan	22 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	43 Participants n=10 Participants
Region of Enrollment Brazil	5 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	9 Participants n=10 Participants
Region of Enrollment Poland	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=10 Participants
Region of Enrollment Italy	13 Participants n=5 Participants	9 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	22 Participants n=10 Participants
Region of Enrollment Israel	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Region of Enrollment France	34 Participants n=5 Participants	17 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	51 Participants n=10 Participants
Region of Enrollment Germany	12 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	23 Participants n=10 Participants

PRIMARY outcome

Timeframe: From Date of Randomization to Death from Any Cause (Up to 28 Months)

Population: All randomized participants. Participants were censored in Ramucirumab arm = 50 and Placebo arm = 21. All randomized participants (including the censored participants) were included in the analyses.

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 + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Overall Survival (OS)	8.51 Months Interval 7.0 to 10.58	7.29 Months Interval 5.42 to 9.07

SECONDARY outcome

Timeframe: From Randomization to Objective Progression or Death from Any Cause (Up to 28 Months)

Population: All randomized participants. Participants were censored in the Ramucirumab arm = 25 and in the Placebo arm = 9. All randomized participants (including the censored participants) were included in the analyses.

Progression-free survival is defined as time from the date of randomization to the date of first observation of objective progression or death from any cause.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Progression Free Survival (PFS)	2.83 Months Interval 2.76 to 4.11	1.61 Months Interval 1.45 to 2.69

SECONDARY outcome

Timeframe: From Randomization to Objective Progression (Up to 28 Months)

Population: All randomized participants.

Time to radiographic progression is defined as the time from the date of randomization to the date of first observation of objective progression.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Time to Radiographic Progression	3.02 Months Interval 2.79 to 4.17	1.61 Months Interval 1.45 to 2.73

SECONDARY outcome

Timeframe: From Randomization to Objective Progression (Up to 28 Months)

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

Objective response rate is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is the disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)	4.6 percentage of participants	1.1 percentage of participants

SECONDARY outcome

Timeframe: Predose, Weeks 2, 6, 12 and 18, Day 1; Up to 3 Days Before Infusion (14-Day Cycles)

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

PK Cmin of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=195 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion Week 0	NA nanogram/milliliter (ng/mL) Geometric Coefficient of Variation NA 1 trough concentrations that was reported below the limit of quantitation were treated as missing for the concentration summaries.	—
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion Week 2	23.5 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 57	—
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion Week 6	44.1 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 60	—
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion Week 12	60.2 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 46	—
Pharmacokinetics (PK): Minimum Serum Concentration (Cmin) Before 2nd, 4th, 7th, and 10th Infusion Week 18	63.2 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 40	—

SECONDARY outcome

Timeframe: Weeks 0, 2, 6, 12 and 18, Day 1; 1 hour to 1.5 hours Post End of Infusion (14 day-Cycles)

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

PK Cmax of Ramucirumab Blood samples were collected at specified time points, and in the event of an infusion-related reaction, for assessment of ramucirumab serum concentrations.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=195 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion Week 0	156 ng/mL Geometric Coefficient of Variation 22	—
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion Week 2	181 ng/mL Geometric Coefficient of Variation 24	—
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion Week 6	205 ng/mL Geometric Coefficient of Variation 24	—
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion Week 12	221 ng/mL Geometric Coefficient of Variation 24	—
PK: Serum Concentration Maximum (Cmax) After 1st, 2nd, 4th, 7th and 10th Ram Infusion Week 18	228 ng/mL Geometric Coefficient of Variation 22	—

SECONDARY outcome

Timeframe: Predose Cycle 1: 7 Days prior to First Infusion, Cycle 4: 3 Days Prior to Infusion, Cycle 7 through Follow Up (Up to 28 Months)

Population: All randomized participants who received at least one dose of study drug and had evaluable anti-ramucirumab data.

Percentage of participants with positive treatment emergent anti-drug antibodies was summarized by treatment group. A treatment-emergent ADA (TEADA) was defined as: having a negative ADA at baseline and an ADA titer greater than or equal to 1:20 (that is (i.e.), greater than 2-fold from the minimal required dilution of 1:10) any time post baseline (i.e., treatment-induced); or a 4-fold or greater change in ADA titer from baseline for participants that had a detectable ADA titer at baseline (i.e., treatment boosted).

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=161 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=76 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Percentage of Participants With Anti-Ramucirumab Antibodies	5.0 percentage of participants	9.2 percentage of participants

SECONDARY outcome

Timeframe: From Randomization to the First Date of Deterioration Observation (≥ 3-point decrease) (Up to 28 Months)

Population: All randomized participants who had evaluable FHSI-8 data.

The FACT Hepatobiliary Symptom Index (FHSI-8) is a instrument with specific focus regarding the most frequent and concerning symptoms experienced by participants with hepatobiliary malignancies, including lack of energy, nausea, pain, weight loss, pain in back, fatigue, jaundice, stomach pain or discomfort. The (FHSI-8) questionnaire was used to assess the time to deterioration of FSHI-8 total score issued from the date of randomization to the first date observing deterioration, with the deterioration threshold defined as a decrease ≥ 3-points from baseline. In case of no deterioration, the participants were censored at the time of the last FSHI-8 item recording. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. Kaplan-Meier method Hazard ratio was used to estimate (Ramucirumab versus Placebo) and 95% Confidence Interval (CI) (Wald) were estimated from un-stratified/stratified Cox model.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Time to Deterioration of Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)	3.71 Months Interval 2.79 to 4.4	2.79 Months Interval 1.64 to 2.89

SECONDARY outcome

Timeframe: From Randomization through End of Study (Up to 28 Months)

Population: All randomized participants and had evaluable EQ-5D-5L data.

The EQ-5D-5L is a nonspecific and standardized instrument for use as a measure of self-reported health status (EuroQol Group 1990; Herdman et al. 2011). Participants completed the 5-level (no problems, slight problems, moderate problems, severe problems, and extreme problems), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D-5L health state scale ranges from 0 to 100 and is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a continuum ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Change From Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire	-0.105 units on a scale Standard Deviation 0.201	-0.099 units on a scale Standard Deviation 0.170

SECONDARY outcome

Timeframe: From Randomization through First Date of Deterioration Observation (ECOG PS≥2) (Up to 28 Months)

Population: All randomized participants and had evaluable ECOG data. Censored participants without any post baseline assessments at randomization date were in the Ramucirumab + BSC arm = 141 and the Placebo + BSC arm =75. All randomized participants (including the censored participants) were included in the analyses.

Time to deterioration in ECOG PS is defined as the time from the date of randomization to the first date observing ECOG PS 2 (ie, deterioration from baseline status of 0 [fully active] or 1 [restricted in physically strenuous activity but ambulatory and able to carry out light work]). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. Assessments included ECOG Performance Status (PS): 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 self-care. Totally confined to bed or chair, 5- Dead.

Outcome measures

Measure	Ramucirumab + Best Supportive Care (BSC) n=197 Participants 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo + BSC n=95 Participants Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Time to Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)	NA Months Interval 9.33 to The median and upper limit 95% confidence interval upper limit had insufficient events to perform a meaningful statistical evaluation.	NA Months Interval 5.26 to The median and upper limit 95% confidence interval had insufficient events to perform a meaningful statistical evaluation.

Adverse Events

Ramucirumab + BSC

Serious events: 72 serious events

Other events: 189 other events

Deaths: 162 deaths

Placebo+BSC

Serious events: 27 serious events

Other events: 77 other events

Deaths: 76 deaths

Open Label Ramucirumab + BSC

Serious events: 18 serious events

Other events: 40 other events

Deaths: 33 deaths

Ramucirumab MEE Cohort

Serious events: 10 serious events

Other events: 39 other events

Deaths: 35 deaths

Placebo MEE Cohort

Serious events: 3 serious events

Other events: 17 other events

Deaths: 18 deaths

Serious adverse events

Measure	Ramucirumab + BSC n=197 participants at risk 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo+BSC n=95 participants at risk Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.	Open Label Ramucirumab + BSC n=47 participants at risk 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Ramucirumab MEE Cohort n=39 participants at risk 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo MEE Cohort n=21 participants at risk Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
General disorders Pyrexia	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Acute hepatic failure	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Cholestasis	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Anaemia	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Neutropenia	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Splenic infarction	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Acute coronary syndrome	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Angina pectoris	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Cardiac arrest	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Cardiac disorders Myocardial infarction	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal hernia	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain upper	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Ascites	3.0% 6/197 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Colitis	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Constipation	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Enterocolitis	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastric haemorrhage	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastric perforation	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastric ulcer	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastric varices haemorrhage	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastroduodenal ulcer	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Melaena	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Mouth ulceration	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Nausea	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Oesophageal haemorrhage	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Oesophageal varices haemorrhage	1.0% 2/197 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Rectal haemorrhage	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Varices oesophageal	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Asthenia	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders General physical health deterioration	1.0% 2/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Generalised oedema	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Multiple organ dysfunction syndrome	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Oedema peripheral	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Pain	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Hepatic pain	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Hepatorenal syndrome	1.0% 2/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Jaundice	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Immune system disorders Anaphylactic reaction	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Abdominal infection	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Anal abscess	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Appendicitis	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Gastroenteritis	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Infection	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Influenza	1.0% 2/197 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Lower respiratory tract infection	1.0% 2/197 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Peritonitis	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 2/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pleural infection	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pneumonia	2.5% 5/197 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Post procedural infection	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Post procedural pneumonia	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Respiratory tract infection	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Sepsis	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Septic shock	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Hip fracture	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Aspartate aminotransferase increased	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Aspiration pleural cavity	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood bilirubin increased	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations General physical condition abnormal	0.51% 1/197 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Dehydration	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Back pain	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Muscular weakness	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liver carcinoma ruptured	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour rupture	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Cerebral ischaemia	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Cerebrovascular accident	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Coma hepatic	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Epilepsy	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Hepatic encephalopathy	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Somnolence	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Syncope	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Anxiety	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Confusional state	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Mental status changes	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Acute kidney injury	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Haematuria	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Nephrotic syndrome	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Renal failure	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 3/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 2/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Surgical and medical procedures Tumour excision	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Deep vein thrombosis	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Haemorrhage	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Hypertensive crisis	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Thrombophlebitis migrans	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Other adverse events

Measure	Ramucirumab + BSC n=197 participants at risk 8 milligrams per kilogram (mg/kg) ramucirumab administered as an intravenous (IV) injection on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo+BSC n=95 participants at risk Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.	Open Label Ramucirumab + BSC n=47 participants at risk 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Ramucirumab MEE Cohort n=39 participants at risk 8 mg/kg ramucirumab administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met.	Placebo MEE Cohort n=21 participants at risk Placebo administered IV on day 1 of each 14 day cycle. Participants may continue treatment until discontinuation criteria are met. Participants still on treatment at the time of study completion may have the option to crossover to the ramucirumab arm.
Blood and lymphatic system disorders Anaemia	9.6% 19/197 • Number of events 28 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.3% 6/95 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.9% 7/39 • Number of events 13 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Blood and lymphatic system disorders Thrombocytopenia	3.6% 7/197 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal distension	8.1% 16/197 • Number of events 18 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.3% 4/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain	18.3% 36/197 • Number of events 46 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.6% 12/95 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.9% 7/39 • Number of events 10 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Abdominal pain upper	5.1% 10/197 • Number of events 10 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Ascites	17.3% 34/197 • Number of events 47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 7/95 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.8% 6/47 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.9% 7/39 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Constipation	13.7% 27/197 • Number of events 33 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	18.9% 18/95 • Number of events 19 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	16.8% 33/197 • Number of events 46 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.7% 14/95 • Number of events 18 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	19.1% 9/47 • Number of events 13 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Mouth haemorrhage	2.0% 4/197 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Mouth ulceration	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.3% 4/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Nausea	18.8% 37/197 • Number of events 47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.5% 10/95 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.8% 6/47 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.3% 4/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Gastrointestinal disorders Vomiting	10.2% 20/197 • Number of events 24 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 7/95 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.3% 3/21 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Asthenia	8.6% 17/197 • Number of events 41 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Chills	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Face oedema	2.0% 4/197 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Fatigue	27.4% 54/197 • Number of events 79 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	16.8% 16/95 • Number of events 23 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.9% 7/47 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Influenza like illness	5.1% 10/197 • Number of events 10 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Malaise	8.1% 16/197 • Number of events 19 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.8% 5/39 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Oedema	3.0% 6/197 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Oedema peripheral	26.4% 52/197 • Number of events 69 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	13.7% 13/95 • Number of events 13 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.9% 7/47 • Number of events 10 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	15.4% 6/39 • Number of events 13 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Pyrexia	9.6% 19/197 • Number of events 23 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	15.4% 6/39 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.3% 3/21 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Hepatic function abnormal	2.0% 4/197 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Hepatic pain	1.0% 2/197 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.3% 3/21 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Hepatobiliary disorders Portal hypertension	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Pneumonia	2.0% 4/197 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	5.6% 11/197 • Number of events 18 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Alanine aminotransferase increased	3.6% 7/197 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	20.5% 8/39 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	23.8% 5/21 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Aspartate aminotransferase increased	8.1% 16/197 • Number of events 27 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.5% 10/95 • Number of events 15 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	38.5% 15/39 • Number of events 22 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	33.3% 7/21 • Number of events 9 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Bilirubin conjugated increased	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.3% 3/21 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood albumin decreased	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.3% 4/39 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood alkaline phosphatase increased	2.0% 4/197 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 2/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.6% 1/39 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood bilirubin increased	10.7% 21/197 • Number of events 39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.4% 8/95 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.6% 5/47 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	28.2% 11/39 • Number of events 27 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	28.6% 6/21 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood creatinine increased	4.6% 9/197 • Number of events 15 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Blood urea increased	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Gamma-glutamyltransferase increased	1.0% 2/197 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	23.8% 5/21 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Neutrophil count decreased	6.1% 12/197 • Number of events 30 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	15.4% 6/39 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	14.3% 3/21 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Platelet count decreased	11.7% 23/197 • Number of events 72 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 2/95 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.8% 6/47 • Number of events 22 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	35.9% 14/39 • Number of events 27 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Urinary occult blood positive	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 9 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations Weight decreased	11.2% 22/197 • Number of events 25 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.3% 6/95 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations White blood cell count decreased	3.6% 7/197 • Number of events 26 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	15.4% 6/39 • Number of events 10 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Investigations White blood cells urine positive	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	24.9% 49/197 • Number of events 60 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	20.0% 19/95 • Number of events 19 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.8% 6/47 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	23.8% 5/21 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyperkalaemia	6.6% 13/197 • Number of events 21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyperuricaemia	0.51% 1/197 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypoalbuminaemia	10.7% 21/197 • Number of events 29 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 4/95 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	35.9% 14/39 • Number of events 24 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	19.0% 4/21 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hypocalcaemia	2.5% 5/197 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/95 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Metabolism and nutrition disorders Hyponatraemia	5.6% 11/197 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.7% 3/39 • Number of events 9 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 14/197 • Number of events 21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Back pain	10.2% 20/197 • Number of events 23 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 7/95 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.3% 2/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.0% 4/197 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.4% 8/95 • Number of events 9 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/47 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Dizziness	4.6% 9/197 • Number of events 10 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.4% 8/95 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Headache	14.2% 28/197 • Number of events 36 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Psychiatric disorders Insomnia	10.7% 21/197 • Number of events 24 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.3% 6/95 • Number of events 8 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Haematuria	0.00% 0/197 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 2/95 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 2/39 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Renal and urinary disorders Proteinuria	21.8% 43/197 • Number of events 74 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.2% 4/95 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	25.5% 12/47 • Number of events 21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	25.6% 10/39 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Cough	10.7% 21/197 • Number of events 26 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.3% 6/95 • Number of events 7 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.6% 5/47 • Number of events 6 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	10.3% 4/39 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	19.0% 4/21 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.1% 12/197 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 1/95 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	2.1% 1/47 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.1% 16/197 • Number of events 19 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.4% 8/95 • Number of events 9 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.7% 27/197 • Number of events 31 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	3.2% 3/95 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Pruritus	7.6% 15/197 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 3/47 • Number of events 3 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/21 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Skin and subcutaneous tissue disorders Rash	7.1% 14/197 • Number of events 19 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	5.3% 5/95 • Number of events 5 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	8.5% 4/47 • Number of events 4 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	0.00% 0/39 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	4.8% 1/21 • Number of events 1 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
Vascular disorders Hypertension	25.4% 50/197 • Number of events 79 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	12.6% 12/95 • Number of events 13 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	23.4% 11/47 • Number of events 16 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	17.9% 7/39 • Number of events 12 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.	9.5% 2/21 • Number of events 2 • Baseline up to 3.2 years All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: (800) 545-5979

Email: ClinicalTrials.gov@Lilly.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60