Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) in Combination With Xelox and Tarceva in Patients With Metastatic Colorectal Cancer. (NCT NCT01135498)

NCT ID: NCT01135498

Last Updated: 2015-02-06

Results Overview

Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 90 participants
• Primary outcome timeframe: Start of study to approximately 4 years
• Results posted on: 2015-02-06

Participant Flow

Participant milestones

Measure	Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) and oxaliplatin 130 mg per square meter (mg/m\^2) IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, orally (PO), every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.
Overall Study STARTED	90
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	90

Reasons for withdrawal

Measure	Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) and oxaliplatin 130 mg per square meter (mg/m\^2) IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, orally (PO), every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.
Overall Study Adverse Event	20
Overall Study Progressive disease	38
Overall Study Investigator judgement	25
Overall Study Withdrawal by Subject	4
Overall Study Death	1
Overall Study Ongoing at time of analysis	2

Baseline Characteristics

A Study of Avastin (Bevacizumab) in Combination With Xelox and Tarceva in Patients With Metastatic Colorectal Cancer.

Baseline characteristics by cohort

Measure	Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=90 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.
Age, Continuous	59.23 years STANDARD_DEVIATION 8.18 • n=93 Participants
Sex: Female, Male Female	29 Participants n=93 Participants
Sex: Female, Male Male	61 Participants n=93 Participants

PRIMARY outcome

Timeframe: Start of study to approximately 4 years

Population: ITT population

Disease progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) as a 20 percent (%) increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=90 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Percentage of Participants With Disease Progression or Death

61.1 percentage of participants

PRIMARY outcome

Timeframe: From study start up to approximately 4 years

Population: ITT population

Progression-free survival was defined as the time from the date of informed consent until the date when the participant had progression of disease or died from disease progression. Participants who received surgical treatment after treatment ended were censored at the time of surgery. Participants who left the study for reasons other than progression of the disease were censored on the date on which they received a later antitumor therapy (with the same or different drugs, radiotherapy, or surgery).

Outcome measures

Measure

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=90 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Progression-Free Survival

9.18 months Interval 7.86 to 11.87

SECONDARY outcome

Timeframe: From study start up to approximately 4 years

Population: Response-Evaluable population: all enrolled participants who received at least 3 cycles of treatment, had all baseline lesions evaluated at least once after receiving the third cycle (using same technique as at baseline), and were without major violations of the study protocol.

Percentage of participants with objective response based assessment of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must have decreased to normal (short axis less than [<]10 millimeters [mm]) and no new lesions. PR was defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

Outcome measures

Measure

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=84 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR])

55.95 percentage of participants

SECONDARY outcome

Timeframe: From study start up to approximately 4 years

Population: Response-Evaluable population

Percent of participants with confirmed CR, PR, or NC. Per RECIST version (v)1.0: CR was defined as disappearance of all target and non-target lesions. PR was defined as ≥30% decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions. NC was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non-target lesions.

Outcome measures

Measure

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=84 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Percentage of Participants Achieving Disease Control (CR, PR, or No Change [NC])

92.86 percentage of participants

SECONDARY outcome

Timeframe: From study start up to approximately 4 years

Population: ITT population

Outcome measures

Measure

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=90 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Percentage of Participants Who Died

58.89 percentage of participants

SECONDARY outcome

Timeframe: From study start up to approximately 4 years

Population: ITT population

Overall survival was defined as the time from the date of informed consent to the date of death (regardless of the cause of death). There was no restriction; survival was calculated until the date of death, even if another line of treatment was received, or until the date censored (last contact with the participant even if drugs different from the study treatment schedule were received). For all participants, survival information was collected until the date of death, the last contact, or the last follow-up.

Outcome measures

Measure

Bevacizumab+Oxaliplatin+Capecitabine/Bevacizumab+Erlotinib n=90 Participants Cycles 1-6 (3-week cycles): participants received bevacizumab 7.5 mg/kg IV and oxaliplatin 130 mg/m\^2 IV on Day 1 and capecitabine 1000 mg/m\^2, tablet, PO, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. Cycles 7 and beyond (3-week cycles): If all 6 cycles were tolerated with no disease progression, participants then received bevacizumab 7.5 mg/kg IV on Day 1 and erlotinib 150 mg tablets, PO, once daily. This cycle was repeated every 3 weeks until disease progression.

Overall Survival (OS)

25.79 months Interval 17.99 to 30.92

Adverse Events

Bevacizumab+Eloxatin+Capecitabine/Bevacizumab+Erlotinib

Serious events: 33 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab+Eloxatin+Capecitabine/Bevacizumab+Erlotinib n=90 participants at risk A cycle was defined as the following: participants received 7.5 mg/kg bevacizumab, IV on Day 1; 130 mg/m\^2 eloxatin tablets, orally, on Days 1 through 14; and 1000 mg/m\^2 capecitabine tablets, orally, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. If all 6 cycles were tolerated with no disease progression, participants then received 7.5 mg/kg bevacizumab, IV on Day 1 and 150 mg erlotinib tablets, orally, once daily. This cycle was repeated every 3 weeks until disease progression.
Blood and lymphatic system disorders Neutropenia	7.8% 7/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Anaemia	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Leukopenia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Cardiac disorders Myocardial ischaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Diarrhoea	20.0% 18/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Vomiting	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal pain	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Nausea	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Rectal haemorrhage	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Subileus	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Enteritis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Intestinal obstruction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Colitis ischaemic	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal pain upper	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Enterocutaneous fistula	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Large intestine perforation	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal distension	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Asthenia	12.2% 11/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders General physical health deterioration	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Mucosal inflammation	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Adverse drug reaction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Pyrexia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Jaundice cholestatic	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Hepatotoxicity	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Immune system disorders Drug hypersensitivity	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Infection	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Respiratory tract infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Perirectal abscess	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Folliculitis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Pneumonia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Urinary tract infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Gastroenteritis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Injury, poisoning and procedural complications Seroma	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Gamma-glutamyltransferase	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood potassium decreased	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Anorexia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Dehydration	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour perforation	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Dysaesthesia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Headache	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Psychiatric disorders Anxiety	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Psychiatric disorders Confusional state	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Acute prerenal failure	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Hydronephrosis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Ureteric obstruction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Rash	6.7% 6/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Acne	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Erythema	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Toxic skin eruption	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Skin reaction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Skin toxicity	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Vascular disorders Hypertension	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Vascular disorders Deep vein thrombosis	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.

Other adverse events

Measure	Bevacizumab+Eloxatin+Capecitabine/Bevacizumab+Erlotinib n=90 participants at risk A cycle was defined as the following: participants received 7.5 mg/kg bevacizumab, IV on Day 1; 130 mg/m\^2 eloxatin tablets, orally, on Days 1 through 14; and 1000 mg/m\^2 capecitabine tablets, orally, every 12 hours on Days 1 through 14. The cycle was repeated every 21 days for a maximum of 6 cycles. If all 6 cycles were tolerated with no disease progression, participants then received 7.5 mg/kg bevacizumab, IV on Day 1 and 150 mg erlotinib tablets, orally, once daily. This cycle was repeated every 3 weeks until disease progression.
Blood and lymphatic system disorders Neutropenia	27.8% 25/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Anaemia	20.0% 18/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Thrombocytopenia	14.4% 13/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Leukopenia	13.3% 12/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Febrile neutropenia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Neutrophilia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Blood and lymphatic system disorders Thrombocythaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Cardiac disorders Tachycardia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Cardiac disorders Myocardial ischaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Ear and labyrinth disorders Vertigo	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Eye disorders Conjunctivitis	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Eye disorders Lacrimation increased	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Eye disorders Xerophthalmia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Eye disorders Conjunctival haemorrhage	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Eye disorders Ocular icterus	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Eye disorders Scotoma	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Diarrhoea	62.2% 56/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Nausea	45.6% 41/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Vomiting	40.0% 36/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal pain	34.4% 31/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Constipation	17.8% 16/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Stomatitis	13.3% 12/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Rectal haemorrhage	10.0% 9/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal pain upper	10.0% 9/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Gingival bleeding	6.7% 6/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Odynophagia	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Rectal tenesmus	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Dry mouth	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal discomfort	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Subileus	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Epigastric discomfort	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal distension	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Flatulence	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Proctalgia	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Anal ulcer	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Dysphagia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Dyspepsia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Lip ulceration	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Enteritis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Pancreatitis acute	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Intestinal obstruction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Gastrointestinal mucositis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Toothache	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Colitis ischaemic	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Aerophagia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Atrophy of tongue papillae	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Enterocutaneous fistula	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Abdominal pain lower	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Anal discomfort	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Haemorrhoids	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Large intestine perforation	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Haematochezia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Asthenia	76.7% 69/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Pyrexia	23.3% 21/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Mucosal inflammation	20.0% 18/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Pain	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Oedema	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Oedema peripheral	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders General physical health deterioration	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Face oedema	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Mucosal dryness	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Hernia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Adverse drug reaction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Infusion site pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
General disorders Temperature intolerance	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Hepatomegaly	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Jaundice cholestatic	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Hepatic pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Jaundice	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Hepatobiliary disorders Hepatotoxicity	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Immune system disorders Drug hypersensitivity	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Immune system disorders Hypersensitivity	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Infection	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Respiratory tract infection	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Cellulitis	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Folliculitis	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Oral infection	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Nasopharyngitis	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Urinary tract infection	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Paronychia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Escherichia urinary tract infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Perirectal abscess	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Abscess limb	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Nail infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Ear infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Skin infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Pneumonia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Upper respiratory tract infection	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Influenza	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Pharyngitis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Furuncle	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Gastroenteritis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Infections and infestations Subcutaneous abscess	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Injury, poisoning and procedural complications Fall	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Injury, poisoning and procedural complications Injury	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Injury, poisoning and procedural complications Seroma	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Injury, poisoning and procedural complications Hand fracture	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Injury, poisoning and procedural complications Contusion	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Weight decreased	5.6% 5/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Aspartate aminotransferase increased	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Gamma-glutamyltransferase	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Alanine aminotransferase increased	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood lactate dehydrogenase	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood alkaline phosphatase increased	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood potassium decreased	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Weight increased	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Platelet count decreased	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Alanine aminotransferase	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood glucose abnormal	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood bilirubin increased	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Investigations Blood lactate dehydrogenase increased	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Anorexia	38.9% 35/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Decreased appetite	8.9% 8/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Hyperglycaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Hypoglycaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Hyperuricaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Dehydration	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Metabolism and nutrition disorders Hypomagnesaemia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Back pain	8.9% 8/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 6/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Bone pain	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Arthralgia	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Myalgia	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Muscle tightness	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Shoulder pain	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Osteoarthritis	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Muscle contracture	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Chest wall pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Trismus	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Groin pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Neck pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Musculoskeletal and connective tissue disorders Buttock pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour perforation	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Paraesthesia	38.9% 35/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Neurotoxicity	35.6% 32/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Dysaesthesia	26.7% 24/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Dysgeusia	8.9% 8/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Headache	7.8% 7/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Neuropathy	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Aphonia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Tremor	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Dizziness	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Ageusia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Hypoaesthesia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Parosmia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Nervous system disorders Somnolence	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Psychiatric disorders Insomnia	6.7% 6/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Psychiatric disorders Anxiety	5.6% 5/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Psychiatric disorders Depression	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Psychiatric disorders Confusional state	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Proteinuria	10.0% 9/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Dysuria	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Acute prerenal failure	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Renal colic	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Urinary incontinence	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Hydronephrosis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Ureteric obstruction	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Renal and urinary disorders Renal failure	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Reproductive system and breast disorders Amenorrhoea	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Reproductive system and breast disorders Perineal pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Epistaxis	15.6% 14/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 5/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Dysphonia	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Hiccups	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Laryngospasm	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Pharyngeal erythema	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Rash	42.2% 38/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	32.2% 29/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Acne	8.9% 8/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Dry skin	5.6% 5/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Erythema	5.6% 5/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Skin reaction	4.4% 4/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Pruritus	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Nail disorder	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Skin toxicity	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Dermatitis	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Skin fissures	2.2% 2/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Leukocytoclastic vasculitis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Alopecia	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Toxic skin eruption	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Plantar erythema	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Nail dystrophy	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Subcutaneous nodule	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Acanthosis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Night sweats	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Skin and subcutaneous tissue disorders Onycholysis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Vascular disorders Hypertension	16.7% 15/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Vascular disorders Deep vein thrombosis	3.3% 3/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Vascular disorders Hypertensive crisis	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.
Vascular disorders Hypotension	1.1% 1/90 • Participants were monitored for adverse events (AEs) from the first dose of study drug until the end of the study. An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A separate analysis of nonserious AEs was not performed, therefore the AE section includes all AEs reported during the study, not just nonserious events.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request the Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER