Trial Outcomes & Findings for Pemetrexed and Best Supportive Care Versus Placebo and Best Supportive Care in Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00102804)

NCT ID: NCT00102804

Last Updated: 2014-12-29

Results Overview

PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant's last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 663 participants
• Primary outcome timeframe: Randomization to measured PD or death from any cause (up to 41 months)
• Results posted on: 2014-12-29

Participant Flow

Participants who signed the informed consent form (ICF) and completed the randomized process are presented in the participant flow by the treatment arm to which they were randomized. Participants who did not sign the ICF or complete the randomization process were removed from the database and excluded from all analyses.

Participant milestones

Measure	Pemetrexed and BSC Pemetrexed: 500 milligrams per square meter (mg/m\^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Overall Study STARTED	441	222
Overall Study Received at Least 1 Dose of Study Drug	434	222
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	441	222

Reasons for withdrawal

Measure	Pemetrexed and BSC Pemetrexed: 500 milligrams per square meter (mg/m\^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Overall Study Progressive Disease (PD)	307	196
Overall Study Withdrawal by Subject	46	7
Overall Study Adverse Event	37	3
Overall Study Physician Decision	24	6
Overall Study Death	5	6
Overall Study Enrollment Criteria Not Met	6	0
Overall Study Lost to Follow-up	4	1
Overall Study Protocol Violation	2	1
Overall Study Satisfactory Response	2	0
Overall Study Sponsor Decision	1	0
Overall Study Alive, Receiving Treatment	7	2

Baseline Characteristics

Pemetrexed and Best Supportive Care Versus Placebo and Best Supportive Care in Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Measure	Pemetrexed and BSC n=441 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=222 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Total n=663 Participants Total of all reporting groups
Age, Continuous	60.6 years n=5 Participants	60.4 years n=7 Participants	60.6 years n=5 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	61 Participants n=7 Participants	180 Participants n=5 Participants
Sex: Female, Male Male	322 Participants n=5 Participants	161 Participants n=7 Participants	483 Participants n=5 Participants
Race/Ethnicity, Customized Aboriginal	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized African	6 participants n=5 Participants	0 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Caucasian	279 participants n=5 Participants	149 participants n=7 Participants	428 participants n=5 Participants
Race/Ethnicity, Customized East Asian	104 participants n=5 Participants	50 participants n=7 Participants	154 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	13 participants n=5 Participants	6 participants n=7 Participants	19 participants n=5 Participants
Race/Ethnicity, Customized West Asian	39 participants n=5 Participants	16 participants n=7 Participants	55 participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	12 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment Taiwan	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Greece	18 participants n=5 Participants	9 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Spain	30 participants n=5 Participants	19 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment Turkey	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Austria	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Italy	18 participants n=5 Participants	16 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment India	39 participants n=5 Participants	16 participants n=7 Participants	55 participants n=5 Participants
Region of Enrollment Hungary	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Czech Republic	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Poland	25 participants n=5 Participants	11 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Brazil	24 participants n=5 Participants	10 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Croatia	10 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Romania	51 participants n=5 Participants	26 participants n=7 Participants	77 participants n=5 Participants
Region of Enrollment Australia	19 participants n=5 Participants	8 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Bulgaria	11 participants n=5 Participants	8 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Netherlands	10 participants n=5 Participants	4 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Germany	40 participants n=5 Participants	16 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment China	62 participants n=5 Participants	37 participants n=7 Participants	99 participants n=5 Participants
Region of Enrollment Korea, Republic of	37 participants n=5 Participants	9 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to measured PD or death from any cause (up to 41 months)

Population: Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized. Participants censored: N = 123, 36 participants in the pemetrexed and placebo treatment arms, respectively.

PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant's last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Measure	Pemetrexed and BSC n=441 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=222 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Progression-Free Survival (PFS) Time	4.27 months Interval 4.07 to 4.73	2.60 months Interval 1.68 to 2.83

SECONDARY outcome

Timeframe: Randomization to date of death from any cause (up to 41 months)

Population: Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized. Participants censored: N = 138, 48 participants in the pemetrexed and placebo treatment arms, respectively.

OS time was the elapsed time from the date of randomization to the date of death from any cause. OS was censored at the last date of contact for participants who were not known to have died as of the data-inclusion cut-off date for analysis.

Outcome measures

Measure	Pemetrexed and BSC n=441 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=222 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Overall Survival (OS) Time	13.37 months Interval 11.93 to 15.87	10.58 months Interval 8.74 to 12.02

SECONDARY outcome

Timeframe: Randomization to measured PD (up to 41 months)

Population: Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized. Participants censored: N = 145, 40 participants in the pemetrexed and placebo treatment arms, respectively.

TPD was the elapsed time from the date of randomization to the first date of objective PD. TPD was censored at the date of the participant's last tumor assessment for participants who were not known to have PD as of the data-inclusion cut-off date for analysis or who died without objective PD. PD, defined using RECIST v1.0, was at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Measure	Pemetrexed and BSC n=441 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=222 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Time to Objective Progressive Disease (TPD)	4.27 months Interval 4.11 to 4.73	2.60 months Interval 1.68 to 2.83

SECONDARY outcome

Timeframe: Randomization to worsening of each LCSS item (up to 39 months)

Population: Pts who signed ICF and completed randomization, according to treatment randomized. Pts censored: Loss of appetite 236,140; fatigue 237,130; cough 274,146; dyspnea 271,143, hemoptysis 404,198; pain 271,135; symptom distress 247,141; interference with activity level 267,141, global quality of life 262,137 pts in pemetrexed, placebo arm, respectively.

TWS was the elapsed time from the date of randomization to the first date of worsening [defined as a 15-millimeter (mm) increase from baseline based on a 100-mm scale] of each symptom and summary item in the Lung Cancer Symptom Scale (LCSS). The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant (pt) responses to each item were measured using visual analogue scales (VAS) from 0 (for best outcome) to 100 (for worst outcome). TWS was censored at the date of the last LCSS assessment for pts who were not known to have LCSS worsening.

Outcome measures

Measure	Pemetrexed and BSC n=441 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=222 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Time to Worsening of Symptoms (TWS) Loss of appetite	3.78 months Interval 2.86 to 4.44	4.40 months Interval 2.96 to 15.61
Time to Worsening of Symptoms (TWS) Fatigue	3.06 months Interval 2.63 to 5.29	3.09 months Interval 2.43 to 3.98
Time to Worsening of Symptoms (TWS) Cough	6.05 months Interval 4.21 to 7.82	4.67 months Interval 3.06 to 15.61
Time to Worsening of Symptoms (TWS) Dyspnea	5.36 months Interval 4.21 to 10.87	4.40 months Interval 2.83 to 15.61
Time to Worsening of Symptoms (TWS) Hemoptysis	NA months Median (95% confidence interval) TWS for hemoptysis was not calculated due to the high level of censoring.	NA months Median (95% confidence interval) TWS for hemoptysis was not calculated due to the high level of censoring.
Time to Worsening of Symptoms (TWS) Pain	6.11 months Interval 4.57 to 9.56	4.63 months Interval 3.32 to 5.98
Time to Worsening of Symptoms (TWS) Symptomatic distress	4.21 months Interval 3.58 to 5.55	3.78 months Interval 2.99 to 18.53
Time to Worsening of Symptoms (TWS) Interference with activity level	6.51 months Interval 4.34 to 8.18	3.98 months Interval 2.83 to 15.61
Time to Worsening of Symptoms (TWS) Global quality of life	5.75 months Interval 4.37 to 8.41	3.71 months Interval 2.99 to 5.49

SECONDARY outcome

Timeframe: Baseline to measured PD (up to 41 months)

Population: Participants who signed the ICF and completed the randomized process are reported according to the treatment arm to which they were randomized.

Response was defined using RECIST v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined either A) at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or B) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared. The percentage of participants with CR or PR=(Number of participants with CR or PR)/(Number of participants assessed)*100.

Outcome measures

Measure	Pemetrexed and BSC n=441 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=222 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Percentage of Participants With a Complete Response (CR) or Partial Response (PR) (Objective Tumor Response Rate)	6.8 percentage of participants Interval 5.0 to 10.0	1.8 percentage of participants Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: Baseline to study completion (up to 41 Months)

Population: Participants who signed the ICF, completed the randomized process and received at least 1 dose of study drug are reported according to the treatment to which they were received.

Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality. A summary of serious and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Measure	Pemetrexed and BSC n=438 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=218 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Number of Participants With Adverse Events (AEs) SAEs	83 participants	31 participants
Number of Participants With Adverse Events (AEs) Other Non-Serious AEs	386 participants	178 participants

SECONDARY outcome

Timeframe: Baseline through 30 days post discontinuation of study treatment (up to 39 Months)

Population: Participants who signed the ICF, completed the randomization process, had LCSS data at baseline and at least once postdose are reported according to the treatment arm to which they were randomized.

The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using VAS from 0 (for best outcome) to 100 (for worst outcome). The average symptom burden index (ASBI) was the mean of the 6 symptom-specific items. The LCSS total score was the mean of the 9 items.

Outcome measures

Measure	Pemetrexed and BSC n=403 Participants Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=197 Participants Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Interference with activity level (n=400, 197)	10.8 units on a scale Standard Deviation 27.08	9.3 units on a scale Standard Deviation 25.50
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS ASBI (n=392, 195)	3.7 units on a scale Standard Deviation 12.34	3.8 units on a scale Standard Deviation 13.24
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Total LCSS (n=388, 193)	4.07 units on a scale Standard Deviation 12.76	4.04 units on a scale Standard Deviation 13.03
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Loss of appetite (n=403, 197)	7.3 units on a scale Standard Deviation 25.90	10.6 units on a scale Standard Deviation 25.25
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Fatigue (n=403, 197)	10.2 units on a scale Standard Deviation 27.10	10.4 units on a scale Standard Deviation 23.92
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Cough (n=402, 197)	7.6 units on a scale Standard Deviation 20.09	6.7 units on a scale Standard Deviation 23.81
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Dyspnea (n=400, 196)	7.6 units on a scale Standard Deviation 22.50	5.4 units on a scale Standard Deviation 20.44
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Pain (n=401, 197)	5.4 units on a scale Standard Deviation 20.96	4.3 units on a scale Standard Deviation 21.93
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Hemoptysis (n=402, 196)	1.5 units on a scale Standard Deviation 9.41	2.1 units on a scale Standard Deviation 9.23
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Symptom distress (n=401, 196)	6.5 units on a scale Standard Deviation 21.13	8.2 units on a scale Standard Deviation 22.5
Maximum Improvement Over Baseline in Individual Symptom Scores and Quality of Life Using the LCSS Global quality of life (n=401, 195)	10.7 units on a scale Standard Deviation 24.94	10.5 units on a scale Standard Deviation 22.98

Adverse Events

Pemetrexed and BSC

Serious events: 83 serious events

Other events: 386 other events

Deaths: 0 deaths

Placebo and BSC

Serious events: 31 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pemetrexed and BSC n=438 participants at risk Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=218 participants at risk Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Anaemia	1.4% 6/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Anaemia of malignant disease	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Febrile neutropenia	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Leukopenia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Neutropenia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Thrombocytopenia	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Acute myocardial infarction	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Atrial fibrillation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Cardiac failure	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Cardiac disorders Cardio-respiratory arrest	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Myocardial infarction	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Myocardial ischaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Pericardial effusion	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Sinus tachycardia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Vertigo	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Abdominal pain	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Constipation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Dysphagia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Haematemesis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Large intestine perforation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Nausea	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Reflux oesophagitis	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Vomiting	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
General disorders Asthenia	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Chest pain	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Death	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
General disorders Fatigue	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders General physical health deterioration	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Mucosal inflammation	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Multi-organ failure	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
General disorders Performance status decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Pyrexia	0.91% 4/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Bronchitis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Bronchopneumonia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Cellulitis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Erysipelas	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Gastrointestinal infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Herpes zoster	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Oral candidiasis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Pneumonia	2.3% 10/438 • Number of events 10 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Infections and infestations Pulmonary sepsis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Respiratory tract infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Sepsis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Skin infection	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Urinary tract infection	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Urosepsis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Femur fracture	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Rib fracture	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Weight decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Anorexia	0.91% 4/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Dehydration	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypercalcaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypoglycaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Joint effusion	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Myalgia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Pain in extremity	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Convulsion	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Dizziness	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Nervous system disorders Epilepsy	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Headache	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Nervous system disorders Hemiparesis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Hypoaesthesia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Ischaemic stroke	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Paraparesis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Paraplegia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Partial seizures	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Spinal cord compression	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Transient ischaemic attack	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Psychiatric disorders Confusional state	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Renal and urinary disorders Dysuria	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Renal and urinary disorders Nephrolithiasis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Renal failure	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Renal failure acute	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Urinary retention	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Balanitis	0.31% 1/321 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/158 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Cough	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.2% 14/438 • Number of events 14 Participants are reported under the treatment to which they received.	2.8% 6/218 • Number of events 6 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Deep vein thrombosis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Pelvic venous thrombosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Superior vena caval occlusion	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.

Other adverse events

Measure	Pemetrexed and BSC n=438 participants at risk Pemetrexed: 500 mg/m\^2, IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.	Placebo and BSC n=218 participants at risk Placebo: IV administration, q 21 days. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
Eye disorders Pterygium	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Anaemia	14.8% 65/438 • Number of events 97 Participants are reported under the treatment to which they received.	5.5% 12/218 • Number of events 15 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Anaemia of malignant disease	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Febrile neutropenia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Leukopenia	5.7% 25/438 • Number of events 64 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 8 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Lymphadenopathy	0.68% 3/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Lymphopenia	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Neutropenia	4.8% 21/438 • Number of events 66 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 5 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Neutrophilia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Thrombocythaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Blood and lymphatic system disorders Thrombocytopenia	3.9% 17/438 • Number of events 29 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 3 Participants are reported under the treatment to which they received.
Cardiac disorders Arrhythmia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Cardiac disorders Atrial fibrillation	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Atrial tachycardia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Cardiac disorders Bradycardia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Cyanosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Myocardial ischaemia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Cardiac disorders Palpitations	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Cardiac disorders Pericardial effusion	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Cardiac disorders Sinus tachycardia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Cardiac disorders Tachycardia	0.68% 3/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Cerumen impaction	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Deafness	0.46% 2/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Ear discomfort	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Ear pain	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Hypoacusis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Motion sickness	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Tinnitus	1.1% 5/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Ear and labyrinth disorders Vertigo	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Endocrine disorders Goitre	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Endocrine disorders Hyperthyroidism	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Endocrine disorders Hypothyroidism	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Blepharitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Cataract	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Eye disorders Conjunctivitis	4.6% 20/438 • Number of events 24 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Eye disorders Conjunctivitis allergic	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Dry eye	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Eye disorders Eye pain	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Eye swelling	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Eyelid oedema	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Keratoconjunctivitis sicca	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Lacrimation increased	4.6% 20/438 • Number of events 21 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Ocular surface disease	0.68% 3/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Eye disorders Photophobia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Eye disorders Vision blurred	1.8% 8/438 • Number of events 10 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Eye disorders Visual acuity reduced	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Eye disorders Visual disturbance	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Abdominal distension	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Abdominal pain	4.1% 18/438 • Number of events 18 Participants are reported under the treatment to which they received.	3.7% 8/218 • Number of events 8 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Abdominal pain lower	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Abdominal pain upper	1.6% 7/438 • Number of events 7 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 11 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Ascites	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Constipation	13.5% 59/438 • Number of events 85 Participants are reported under the treatment to which they received.	7.8% 17/218 • Number of events 22 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Dental caries	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Diarrhoea	11.9% 52/438 • Number of events 88 Participants are reported under the treatment to which they received.	6.9% 15/218 • Number of events 17 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Dry mouth	2.3% 10/438 • Number of events 10 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Dyspepsia	3.0% 13/438 • Number of events 18 Participants are reported under the treatment to which they received.	2.8% 6/218 • Number of events 21 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Dysphagia	0.91% 4/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Faecal incontinence	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Faecaloma	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Flatulence	0.91% 4/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Gastric disorder	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Gastritis	0.91% 4/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Gingival pain	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Gingivitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Haemorrhoids	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Hiatus hernia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Ileus	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Inflammatory bowel disease	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Lip ulceration	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Mouth ulceration	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Nausea	23.3% 102/438 • Number of events 209 Participants are reported under the treatment to which they received.	10.1% 22/218 • Number of events 24 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Odynophagia	0.91% 4/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Oesophageal haemorrhage	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Oesophagitis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Oral pain	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Paraesthesia oral	0.46% 2/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Periodontal disease	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Rectal haemorrhage	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Stomatitis	4.3% 19/438 • Number of events 22 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Tongue black hairy	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Tongue coated	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Toothache	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Gastrointestinal disorders Vomiting	12.8% 56/438 • Number of events 88 Participants are reported under the treatment to which they received.	4.1% 9/218 • Number of events 12 Participants are reported under the treatment to which they received.
General disorders Asthenia	11.0% 48/438 • Number of events 74 Participants are reported under the treatment to which they received.	4.6% 10/218 • Number of events 11 Participants are reported under the treatment to which they received.
General disorders Axillary pain	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Catheter site erythema	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Chest discomfort	0.68% 3/438 • Number of events 14 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Chest pain	10.0% 44/438 • Number of events 67 Participants are reported under the treatment to which they received.	7.3% 16/218 • Number of events 17 Participants are reported under the treatment to which they received.
General disorders Chills	1.6% 7/438 • Number of events 9 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Condition aggravated	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Cyst	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
General disorders Extravasation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Face oedema	1.4% 6/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
General disorders Facial pain	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Fatigue	33.1% 145/438 • Number of events 227 Participants are reported under the treatment to which they received.	22.5% 49/218 • Number of events 63 Participants are reported under the treatment to which they received.
General disorders Feeling abnormal	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Gait disturbance	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders General physical health deterioration	1.6% 7/438 • Number of events 9 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Influenza like illness	2.3% 10/438 • Number of events 17 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 4 Participants are reported under the treatment to which they received.
General disorders Injection site reaction	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Irritability	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Localised oedema	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Malaise	0.46% 2/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Mucosal inflammation	2.7% 12/438 • Number of events 19 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
General disorders Obstruction	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Oedema	2.7% 12/438 • Number of events 16 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
General disorders Oedema peripheral	6.2% 27/438 • Number of events 34 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 3 Participants are reported under the treatment to which they received.
General disorders Pain	5.5% 24/438 • Number of events 28 Participants are reported under the treatment to which they received.	6.0% 13/218 • Number of events 13 Participants are reported under the treatment to which they received.
General disorders Peripheral coldness	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
General disorders Pyrexia	12.8% 56/438 • Number of events 78 Participants are reported under the treatment to which they received.	11.5% 25/218 • Number of events 33 Participants are reported under the treatment to which they received.
General disorders Swelling	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
General disorders Visceral oedema	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Hepatobiliary disorders Cholelithiasis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Hepatobiliary disorders Hepatic pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Hepatobiliary disorders Hepatitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Hepatobiliary disorders Hepatomegaly	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Hepatobiliary disorders Hyperbilirubinaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Immune system disorders Contrast media allergy	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Immune system disorders Hypersensitivity	1.4% 6/438 • Number of events 8 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Immune system disorders Seasonal allergy	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Abscess	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Bronchitis	3.4% 15/438 • Number of events 17 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Infections and infestations Candidiasis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Cellulitis	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Cystitis	0.46% 2/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Diverticulitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Ear infection	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Erysipelas	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Folliculitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Fungal infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Gastroenteritis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Gastroenteritis viral	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Hepatic infection	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Herpes simplex	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Herpes virus infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Herpes zoster	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Infection	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Infections and infestations Influenza	2.3% 10/438 • Number of events 12 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Laryngitis	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Infections and infestations Lower respiratory tract infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Lung infection	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Nasopharyngitis	3.2% 14/438 • Number of events 17 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Infections and infestations Oral candidiasis	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Oral herpes	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Infections and infestations Otitis media	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Paronychia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Parotitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Pharyngitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Pneumonia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Infections and infestations Pyothorax	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Infections and infestations Respiratory tract infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Respiratory tract infection viral	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Rhinitis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Sinusitis	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Soft tissue infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Tonsillitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Tooth abscess	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Tooth infection	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Infections and infestations Upper respiratory tract infection	3.4% 15/438 • Number of events 20 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Infections and infestations Urinary tract infection	1.1% 5/438 • Number of events 7 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Arterial injury	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Contusion	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Fall	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Fracture	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Incision site pain	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Procedural headache	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Radiation skin injury	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Thermal burn	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Injury, poisoning and procedural complications Wound	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Alanine aminotransferase	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Alanine aminotransferase decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Alanine aminotransferase increased	13.7% 60/438 • Number of events 87 Participants are reported under the treatment to which they received.	4.1% 9/218 • Number of events 11 Participants are reported under the treatment to which they received.
Investigations Aspartate aminotransferase increased	11.9% 52/438 • Number of events 63 Participants are reported under the treatment to which they received.	3.7% 8/218 • Number of events 10 Participants are reported under the treatment to which they received.
Investigations Blood albumin decreased	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood alkaline phosphatase	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Investigations Blood alkaline phosphatase increased	2.7% 12/438 • Number of events 16 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Investigations Blood bicarbonate decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood bilirubin increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood calcium decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood creatinine decreased	0.68% 3/438 • Number of events 10 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Blood creatinine increased	4.8% 21/438 • Number of events 30 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Investigations Blood fibrinogen increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood glucose increased	0.23% 1/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood iron decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood lactate dehydrogenase increased	2.1% 9/438 • Number of events 15 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Blood potassium decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood potassium increased	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood sodium decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood sodium increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Blood uric acid increased	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations C-reactive protein increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Creatinine renal clearance decreased	4.1% 18/438 • Number of events 28 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Investigations Forced expiratory volume decreased	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Gamma-glutamyltransferase increased	1.4% 6/438 • Number of events 7 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 5 Participants are reported under the treatment to which they received.
Investigations Glomerular filtration rate	0.23% 1/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Glomerular filtration rate decreased	1.1% 5/438 • Number of events 10 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Granulocyte count decreased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Granulocyte count increased	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Investigations Haemoglobin	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Haemoglobin decreased	4.3% 19/438 • Number of events 30 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Investigations Neutrophil count decreased	2.5% 11/438 • Number of events 16 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Neutrophil count increased	0.68% 3/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Platelet count	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Platelet count decreased	1.1% 5/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Investigations Platelet count increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 3 Participants are reported under the treatment to which they received.
Investigations Red blood cell count decreased	0.46% 2/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Red blood cell microcytes present	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Renal function test abnormal	0.23% 1/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Sensory level	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Total bile acids increased	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations Transaminases increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Troponin t	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations Weight decreased	3.9% 17/438 • Number of events 20 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Investigations Weight increased	1.1% 5/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Investigations White blood cell count decreased	0.91% 4/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Investigations White blood cell count increased	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 3 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Acidosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Alcohol intolerance	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Alkalosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Anorexia	28.3% 124/438 • Number of events 238 Participants are reported under the treatment to which they received.	18.3% 40/218 • Number of events 43 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Dehydration	1.6% 7/438 • Number of events 8 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Diabetes mellitus	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Fluid retention	0.46% 2/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Glucose tolerance impaired	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypercalcaemia	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 3 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypercholesterolaemia	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypercreatininaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hyperglycaemia	4.1% 18/438 • Number of events 20 Participants are reported under the treatment to which they received.	2.8% 6/218 • Number of events 7 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hyperkalaemia	0.91% 4/438 • Number of events 6 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hyperlipidaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypernatraemia	0.46% 2/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hyperuricaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypoalbuminaemia	0.46% 2/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypocalcaemia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypokalaemia	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hyponatraemia	1.6% 7/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 2 Participants are reported under the treatment to which they received.
Metabolism and nutrition disorders Increased appetite	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Arthralgia	2.7% 12/438 • Number of events 16 Participants are reported under the treatment to which they received.	3.2% 7/218 • Number of events 7 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Arthritis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Back pain	9.4% 41/438 • Number of events 48 Participants are reported under the treatment to which they received.	3.7% 8/218 • Number of events 8 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Bone pain	3.2% 14/438 • Number of events 14 Participants are reported under the treatment to which they received.	4.6% 10/218 • Number of events 10 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Flank pain	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Muscle spasms	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Muscular weakness	1.1% 5/438 • Number of events 6 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.8% 8/438 • Number of events 8 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 5 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.7% 12/438 • Number of events 14 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 6 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Myalgia	3.4% 15/438 • Number of events 17 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 7 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Neck pain	0.68% 3/438 • Number of events 5 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 6 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 11/438 • Number of events 14 Participants are reported under the treatment to which they received.	4.1% 9/218 • Number of events 11 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Pain in jaw	0.46% 2/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Scleroderma	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Musculoskeletal and connective tissue disorders Tendonitis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiolipoma	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	2.5% 11/438 • Number of events 11 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.1% 5/438 • Number of events 5 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 5 Participants are reported under the treatment to which they received.
Nervous system disorders Ageusia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Aphasia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Aphonia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Ataxia	1.1% 5/438 • Number of events 6 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Balance disorder	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Brain injury	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Burning sensation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Cerebral ischaemia	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Nervous system disorders Cognitive disorder	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Coma	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Convulsion	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Depressed level of consciousness	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Disturbance in attention	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Dizziness	7.8% 34/438 • Number of events 39 Participants are reported under the treatment to which they received.	3.2% 7/218 • Number of events 7 Participants are reported under the treatment to which they received.
Nervous system disorders Dysaesthesia	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Dysgeusia	2.3% 10/438 • Number of events 14 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Dysphasia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Formication	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Headache	11.6% 51/438 • Number of events 62 Participants are reported under the treatment to which they received.	8.7% 19/218 • Number of events 26 Participants are reported under the treatment to which they received.
Nervous system disorders Hemicephalalgia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Hemiparesis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Hypoaesthesia	1.1% 5/438 • Number of events 6 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Nervous system disorders Memory impairment	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Neuralgia	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Neuropathy peripheral	2.3% 10/438 • Number of events 11 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Nervous system disorders Neurotoxicity	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Paraesthesia	6.2% 27/438 • Number of events 29 Participants are reported under the treatment to which they received.	5.0% 11/218 • Number of events 12 Participants are reported under the treatment to which they received.
Nervous system disorders Peripheral motor neuropathy	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Peripheral sensory neuropathy	5.0% 22/438 • Number of events 22 Participants are reported under the treatment to which they received.	2.8% 6/218 • Number of events 6 Participants are reported under the treatment to which they received.
Nervous system disorders Poor quality sleep	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Somnolence	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Speech disorder	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Stupor	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Syncope	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Nervous system disorders Syncope vasovagal	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Transient ischaemic attack	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Nervous system disorders Tremor	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Psychiatric disorders Abnormal behaviour	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Psychiatric disorders Agitation	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Psychiatric disorders Anxiety	1.1% 5/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Psychiatric disorders Confusional state	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Psychiatric disorders Depressed mood	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Psychiatric disorders Depression	2.1% 9/438 • Number of events 9 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Psychiatric disorders Insomnia	6.4% 28/438 • Number of events 31 Participants are reported under the treatment to which they received.	3.7% 8/218 • Number of events 8 Participants are reported under the treatment to which they received.
Psychiatric disorders Suicidal ideation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Psychiatric disorders Tic	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Bladder spasm	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Calculus bladder	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Dysuria	0.68% 3/438 • Number of events 8 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Glycosuria	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Haematuria	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Haemorrhage urinary tract	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Renal and urinary disorders Incontinence	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Micturition urgency	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Renal and urinary disorders Nocturia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Pollakiuria	0.68% 3/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Renal failure	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Urinary hesitation	0.23% 1/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Renal and urinary disorders Urinary incontinence	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Renal and urinary disorders Urinary retention	1.1% 5/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Balanitis	0.31% 1/321 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/158 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Breast swelling	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Pelvic pain	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Testicular disorder	0.31% 1/321 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/158 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Testicular pain	0.31% 1/321 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/158 Participants are reported under the treatment to which they received.
Reproductive system and breast disorders Vaginal haemorrhage	1.7% 2/117 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/60 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Cough	21.7% 95/438 • Number of events 118 Participants are reported under the treatment to which they received.	21.6% 47/218 • Number of events 50 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.4% 98/438 • Number of events 118 Participants are reported under the treatment to which they received.	19.7% 43/218 • Number of events 45 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.1% 5/438 • Number of events 8 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.5% 24/438 • Number of events 26 Participants are reported under the treatment to which they received.	4.6% 10/218 • Number of events 11 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Hiccups	2.1% 9/438 • Number of events 17 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	2.3% 10/438 • Number of events 11 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 5 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.68% 3/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Productive cough	2.5% 11/438 • Number of events 15 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/438 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Rales	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.91% 4/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.4% 6/438 • Number of events 6 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Rhonchi	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Respiratory, thoracic and mediastinal disorders Wheezing	0.91% 4/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Acne	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Alopecia	4.8% 21/438 • Number of events 23 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Dermal cyst	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.46% 2/438 • Number of events 6 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Dermatitis exfoliative	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Dermatosis	0.23% 1/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Dry skin	1.1% 5/438 • Number of events 6 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Erythema	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.7% 12/438 • Number of events 15 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Madarosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/438 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Night sweats	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/438 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Periorbital oedema	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Petechiae	0.46% 2/438 • Number of events 5 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Pigmentation disorder	0.91% 4/438 • Number of events 7 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Pruritus	4.1% 18/438 • Number of events 22 Participants are reported under the treatment to which they received.	3.2% 7/218 • Number of events 8 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Pruritus generalised	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Psoriasis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Rash	14.2% 62/438 • Number of events 81 Participants are reported under the treatment to which they received.	6.4% 14/218 • Number of events 16 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Rash pruritic	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Skin discolouration	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Skin exfoliation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.1% 9/438 • Number of events 9 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Skin toxicity	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Swelling face	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Skin and subcutaneous tissue disorders Urticaria	0.23% 1/438 • Number of events 4 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Surgical and medical procedures Medical device implantation	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Surgical and medical procedures Pneumatic compression therapy	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Surgical and medical procedures Tumour excision	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Deep vein thrombosis	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Flushing	1.8% 8/438 • Number of events 10 Participants are reported under the treatment to which they received.	2.3% 5/218 • Number of events 7 Participants are reported under the treatment to which they received.
Vascular disorders Haemorrhage	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Hot flush	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Vascular disorders Hypertension	2.5% 11/438 • Number of events 11 Participants are reported under the treatment to which they received.	1.8% 4/218 • Number of events 4 Participants are reported under the treatment to which they received.
Vascular disorders Hypotension	1.4% 6/438 • Number of events 6 Participants are reported under the treatment to which they received.	1.4% 3/218 • Number of events 3 Participants are reported under the treatment to which they received.
Vascular disorders Orthostatic hypotension	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Vascular disorders Peripheral ischaemia	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Phlebitis	0.46% 2/438 • Number of events 2 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Shock	0.23% 1/438 • Number of events 1 Participants are reported under the treatment to which they received.	0.00% 0/218 Participants are reported under the treatment to which they received.
Vascular disorders Superior vena caval occlusion	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.46% 1/218 • Number of events 1 Participants are reported under the treatment to which they received.
Vascular disorders Thrombosis	0.68% 3/438 • Number of events 3 Participants are reported under the treatment to which they received.	0.92% 2/218 • Number of events 2 Participants are reported under the treatment to which they received.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

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

Restriction type: GT60