Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) Added to a Chemotherapeutic Regimen in Patients With Metastatic Pancreatic Cancer (NCT NCT01214720)

Last Updated: 2014-08-13

Results Overview

Duration of overall survival (OS) was defined as the time between date of randomization and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

607 participants

Primary outcome timeframe

Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized

Results posted on

2014-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab + Gemcitabine + Erlotinib Cycle 1 (8-week cycle): Participants received bevacizumab 5 milligrams per kilogram (mg/kg) intravenously (IV) on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg per square meter (mg/m\^2) IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, orally (PO), once daily (QD) for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Study STARTED	306	301
Overall Study COMPLETED	221	233
Overall Study NOT COMPLETED	85	68

Reasons for withdrawal

Reasons for withdrawal
Measure	Bevacizumab + Gemcitabine + Erlotinib Cycle 1 (8-week cycle): Participants received bevacizumab 5 milligrams per kilogram (mg/kg) intravenously (IV) on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg per square meter (mg/m\^2) IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, orally (PO), once daily (QD) for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Overall Study Alive and still on treatment	34	18
Overall Study Alive and in follow-up	45	48
Overall Study Lost to Follow-up	6	2

Baseline Characteristics

A Study of Avastin (Bevacizumab) Added to a Chemotherapeutic Regimen in Patients With Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab + Gemcitabine + Erlotinib n=306 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=301 Participants Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Total n=607 Participants Total of all reporting groups
Age, Continuous	61.5 years STANDARD_DEVIATION 10.36 • n=5 Participants	61.0 years STANDARD_DEVIATION 10.03 • n=7 Participants	61.2 years STANDARD_DEVIATION 10.19 • n=5 Participants
Sex: Female, Male Female	132 Participants n=5 Participants	113 Participants n=7 Participants	245 Participants n=5 Participants
Sex: Female, Male Male	174 Participants n=5 Participants	188 Participants n=7 Participants	362 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized

Population: ITT population.

Outcome measures

Outcome measures
Measure	Bevacizumab + Gemcitabine + Erlotinib n=306 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=301 Participants Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Duration of Overall Survival - Percentage of Participants With an Event	72.2 percentage of participants	77.4 percentage of participants

PRIMARY outcome

Timeframe: Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized

Population: ITT Population.

Duration of OS was defined as the time between date of randomization and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. Median duration of survival was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Bevacizumab + Gemcitabine + Erlotinib n=306 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=301 Participants Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Duration of Overall Survival - Time to Event	7.1 months Interval 6.4 to 7.8	6.0 months Interval 5.5 to 6.7

SECONDARY outcome

Timeframe: Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized

Population: The analysis of the CBR was dependent on the calculation of analgesic therapy (AT); this calculation relies on established conversion factors for different morphine derivatives (MD). Many MD utilized by participants do not have well-established conversion factors, yielding uninterpretable results. Therefore, CBR was not analyzed in this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, Weeks 8, 16, 24, 32, 40, and every 12 weeks thereafter or until confirmed evidence of disease progression

Population: ITT population.

PFS was defined as the time between the date of randomization and the date of documented progressive disease (PD) defined according to modified Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, or date of death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum (LD) recorded since the treatment started. Participants without an event were censored at the date of last follow up for progression, or date of last available tumor assessment if no further follow up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization.

Outcome measures

Outcome measures
Measure	Bevacizumab + Gemcitabine + Erlotinib n=306 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=301 Participants Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Progression-Free Survival (PFS) - Percentage of Participants With an Event	84.0 percentage of participants	92.4 percentage of participants

SECONDARY outcome

Timeframe: Screening, Weeks 8, 16, 24, 32, 40, and every 12 weeks thereafter or until confirmed evidence of disease progression

Population: ITT Population

PFS was defined as the time between the date of randomization and the date of documented PD (per RECIST), or date of death due to any cause. Data for participants without an event were censored at the date of last follow up for progression, or date of last available tumor assessment if no further follow up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. Median PFS was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Bevacizumab + Gemcitabine + Erlotinib n=306 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=301 Participants Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Progression-Free Survival (PFS) - Time to Event	4.6 months Interval 3.9 to 5.4	3.6 months Interval 3.4 to 3.7

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: ITT Population.

Percentage of participants with CR, PR, or SD according to modified RECIST evaluation at the first postbaseline tumor assessment. CR equaled (=) complete disappearance of all target lesions and non-target disease, with normalization of tumor marker level. PR is greater than or equal to (≥) a 30% decrease of the sum of the LD of all target lesions as referenced to the baseline sum LD of all target lesions. Persistence of one or more non-target lesions(s) and/or maintenance of tumor marker level above normal limits. SD=neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for PD with persistence of one or more non-target lesions(s) and/or maintenance of tumor marker level above normal limits.

Outcome measures

Outcome measures
Measure	Bevacizumab + Gemcitabine + Erlotinib n=306 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=301 Participants Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at First Postbaseline Tumor Assessment	62.1 percentage of participants Interval 56.4 to 67.6	58.5 percentage of participants Interval 52.7 to 64.1

SECONDARY outcome

Timeframe: Weeks 1, 3, 5, 7, and 9

Population: ITT Population. Number (n) = number of participants assessed at a specific visit.

Blood samples were collected from a subgroup of participants, in selected centers for the determination of bevacizumab serum concentration before the first bevacizumab/placebo exposure (Week 1) and at Weeks 3, 5, 7, and 9. Each time blood samples were collected just (preferably within 1 hour) before the start of the study treatment.

Outcome measures

Outcome measures
Measure	Bevacizumab + Gemcitabine + Erlotinib n=78 Participants Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib Week 1 (n=4)	0.52 micrograms/milliliter Standard Deviation 14.98	—
Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib Week 3 (n=78)	27.09 micrograms/milliliter Standard Deviation 18.23	—
Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib Week 5 (n=73)	35.23 micrograms/milliliter Standard Deviation 24.88	—
Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib Week 7 (n=72)	41.19 micrograms/milliliter Standard Deviation 19.68	—
Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib Week 9 (n=61)	44.60 micrograms/milliliter Standard Deviation 22.57	—

Adverse Events

Bevacizumab + Gemcitabine + Erlotinib

Serious events: 139 serious events

Other events: 290 other events

Deaths: 0 deaths

Placebo + Gemcitabine + Erlotinib

Serious events: 119 serious events

Other events: 276 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

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 that 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

Serious adverse events
Measure	Bevacizumab + Gemcitabine + Erlotinib n=297 participants at risk Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=286 participants at risk Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Gastrointestinal disorders Abdominal pain	1.7% 5/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.70% 2/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.0% 3/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	1.4% 4/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Nausea	1.0% 3/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	1.4% 4/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Diarrhoea	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	1.4% 4/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Intestinal obstruction	1.0% 3/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	1.0% 3/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.3% 4/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.70% 2/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Rectal haemorrhage	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.70% 2/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Abdominal pain upper	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Constipation	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastric haemorrhage	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastrointestinal perforation	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Haematemesis	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Ileus	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Ileus paralytic	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Peritonitis	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.70% 2/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Anal fistula	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Anal ulcer	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Ascites	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Duodenal perforation	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Dysphagia	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Faeces discoloured	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastric perforation	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Haematochezia	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Intestinal mass	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Melaena	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Pancreatitis acute	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Peptic ulcer haemorrhage	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Peritoneal haemorrhage	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Sigmoiditis	0.34% 1/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.00% 0/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Subileus	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Infections and infestations Sepsis	2.7% 8/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	2.1% 6/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Infections and infestations Pneumonia	3.0% 9/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.70% 2/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Infections and infestations Abdominal abscess	0.67% 2/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	0.35% 1/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Infections and infestations Bronchitis	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	1.0% 3/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Infections and infestations Septic Shock	0.00% 0/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	1.0% 3/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.

Other adverse events
Measure	Bevacizumab + Gemcitabine + Erlotinib n=297 participants at risk Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.	Placebo + Gemcitabine + Erlotinib n=286 participants at risk Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m\^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal.
Gastrointestinal disorders Diarrhoea	48.8% 145/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	50.3% 144/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Nausea	45.5% 135/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	51.0% 146/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Vomiting	36.4% 108/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	41.3% 118/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Constipation	26.6% 79/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	22.7% 65/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Abdominal pain	15.5% 46/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	13.6% 39/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Abdominal pain upper	11.1% 33/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	10.1% 29/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Stomatitis	11.4% 34/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	6.6% 19/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Dyspepsia	8.4% 25/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	7.0% 20/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Gastrointestinal disorders Flatulence	6.4% 19/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	3.5% 10/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
General disorders Fatigue	35.0% 104/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	33.9% 97/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
General disorders Pyrexia	31.6% 94/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	34.6% 99/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
General disorders Oedema peripheral	17.2% 51/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	17.1% 49/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
General disorders Asthenia	13.8% 41/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	15.4% 44/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
General disorders Mucosal inflammation	8.4% 25/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	10.1% 29/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
General disorders Chills	6.1% 18/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	5.2% 15/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Skin and subcutaneous tissue disorders Rash	49.2% 146/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	44.1% 126/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Skin and subcutaneous tissue disorders Alopecia	13.5% 40/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	15.4% 44/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Skin and subcutaneous tissue disorders Dry skin	12.5% 37/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	8.0% 23/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Skin and subcutaneous tissue disorders Acne	10.1% 30/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	5.9% 17/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Skin and subcutaneous tissue disorders Dermatitis acneiform	8.4% 25/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	6.6% 19/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Skin and subcutaneous tissue disorders Pruritus	7.4% 22/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	6.3% 18/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Blood and lymphatic system disorders Anaemia	25.9% 77/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	33.6% 96/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Blood and lymphatic system disorders Thrombocytopenia	31.3% 93/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	26.6% 76/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Blood and lymphatic system disorders Neutropenia	29.3% 87/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	26.2% 75/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Blood and lymphatic system disorders Leukopenia	5.4% 16/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	7.0% 20/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Respiratory, thoracic and mediastinal disorders Epistaxis	30.0% 89/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	11.2% 32/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.4% 31/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	9.1% 26/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Respiratory, thoracic and mediastinal disorders Cough	8.1% 24/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	8.4% 24/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	5.4% 16/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	2.4% 7/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Nervous system disorders Headache	13.1% 39/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	8.4% 24/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Nervous system disorders Dysgeusia	11.8% 35/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	9.1% 26/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Nervous system disorders Dizziness	6.7% 20/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	8.0% 23/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Metabolism and nutrition disorders Anorexia	21.5% 64/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	23.1% 66/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Psychiatric disorders Insomnia	11.8% 35/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	8.7% 25/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Psychiatric disorders Depression	5.1% 15/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	6.3% 18/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Psychiatric disorders Anxiety	6.1% 18/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	3.5% 10/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Vascular disorders Hypertension	19.5% 58/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	9.8% 28/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Musculoskeletal and connective tissue disorders Back pain	7.1% 21/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	7.7% 22/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 20/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	3.1% 9/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.
Infections and infestations Urinary tract infection	9.8% 29/297 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.	5.9% 17/286 • Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death.