Trial Outcomes & Findings for ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer (NCT NCT01360554)

NCT ID: NCT01360554

Last Updated: 2017-05-24

Results Overview

PFS was defined as the time from randomization to the date of disease progression as by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 878 participants
• Primary outcome timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.
• Results posted on: 2017-05-24

Participant Flow

The study was conducted at 134 sites with 878 participants randomized in a 1:1 ratio to 1 of 2 treatment arms, of these 872 were treated. Eligible participants who provided written informed consent and met all inclusion and exclusion criteria were assigned a Single Subject Identification number and randomized by the central randomization system.

There were no significant study milestones following participant enrollment, but prior to group assignment.

Participant milestones

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Study STARTED	439	439
Overall Study Treated	436	436
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	439	439

Reasons for withdrawal

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Study Death	359	371
Overall Study Lost to Follow-up	4	4
Overall Study Withdrawal by Subject	23	24
Overall Study Study terminated by sponsor	49	37
Overall Study Other, not specified	1	0
Overall Study Randomized but not treated.	3	3

Baseline Characteristics

ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=436 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=436 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Total n=872 Participants Total of all reporting groups
Age, Continuous	63.3 Years STANDARD_DEVIATION 9.57 • n=93 Participants	61.7 Years STANDARD_DEVIATION 9.71 • n=4 Participants	62.5 Years STANDARD_DEVIATION 9.67 • n=27 Participants
Sex: Female, Male Female	150 Participants n=93 Participants	161 Participants n=4 Participants	311 Participants n=27 Participants
Sex: Female, Male Male	286 Participants n=93 Participants	275 Participants n=4 Participants	561 Participants n=27 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

PFS was defined as the time from randomization to the date of disease progression as by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=439 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=439 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Progression-Free Survival (PFS) Per Independent Radiologic Review.	2.6 Months Interval 1.9 to 2.8	2.5 Months Interval 1.9 to 2.8

PRIMARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: ITT population for KRAS-WT participants: all participants who were confirmed as having KRAS-WT tumors, randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=256 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=263 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Progression-Free Survival (PFS) Per Independent Radiologic Review in KRAS Wild-type (WT) Participants.	2.6 Months Interval 1.9 to 2.9	2.5 Months Interval 1.9 to 3.0

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=439 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=439 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
PFS Based on Investigator Review.	1.9 Months Interval 1.9 to 2.6	1.9 Months Interval 1.8 to 2.1

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: ITT population for KRAS-WT participants: all participants who were confirmed as having KRAS-WT tumors, randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=256 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=263 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
PFS Based on Investigator Review in KRAS-WT Participants.	1.9 Months Interval 1.8 to 2.7	1.9 Months Interval 1.8 to 2.6

SECONDARY outcome

Timeframe: From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months.

Population: The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive (ie, at their last known alive date from long term follow-up).

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=439 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=439 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Survival (OS).	7.9 Months Interval 6.8 to 9.0	8.3 Months Interval 7.4 to 9.7

SECONDARY outcome

Timeframe: From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months.

Population: ITT population for KRAS-WT participants: all participants who were confirmed as having KRAS-WT tumors, randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive (ie, at their last known alive date from long term follow-up). Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=256 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=263 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
OS in KRAS-WT Participants.	8.1 Months Interval 6.7 to 9.4	8.5 Months Interval 7.5 to 10.2

SECONDARY outcome

Timeframe: From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

The BOR was the best response per RECIST (version 1.1) criteria as assessed by independent assessment recorded from randomization until disease progression. Per RECIST version 1.1: Complete Response (CR): disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; Partial Response (PR): >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; Progressive Disease (PD): >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=439 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=439 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Best Overall Response (BOR) Per Independent Radiologic Review. Complete response	6 Participants	8 Participants
Best Overall Response (BOR) Per Independent Radiologic Review. Partial response	46 Participants	27 Participants
Best Overall Response (BOR) Per Independent Radiologic Review. Stable/No response	163 Participants	182 Participants
Best Overall Response (BOR) Per Independent Radiologic Review. Objective progression	151 Participants	146 Participants
Best Overall Response (BOR) Per Independent Radiologic Review. Indeterminate	73 Participants	76 Participants

SECONDARY outcome

Timeframe: From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

The BOR was the best response per RECIST (version 1.1) criteria as assessed by investigator assessment recorded from randomization until disease progression. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=439 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=439 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
BOR Per Investigator Review. Complete response	2 Participants	3 Participants
BOR Per Investigator Review. Partial response	57 Participants	42 Participants
BOR Per Investigator Review. Stable/No response	136 Participants	136 Participants
BOR Per Investigator Review. Objective progression	191 Participants	206 Participants
BOR Per Investigator Review. Indeterminate	53 Participants	52 Participants

SECONDARY outcome

Timeframe: From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: DR was analyzed for a subgroup of participants in the ITT population, who had an objective tumor response.

DR was defined as the time from first documentation of response assessed by independent review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=52 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=35 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Duration of Response (DR) Based on Independent Radiologic Review.	9.2 Months Interval 6.9 to 20.2	10.1 Months Interval 5.6 to 14.8

SECONDARY outcome

Timeframe: From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Population: DR was analyzed for a subgroup of participants in the ITT population, who had an objective tumor response.

DR was defined as the time from first documentation of response assessed by investigator review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=59 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=45 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
DR Based on Investigator Review.	10.4 Months Interval 7.4 to 16.6	9.2 Months Interval 6.2 to 11.3

SECONDARY outcome

Timeframe: Baseline up to Cycle 5 Day 1

Population: Participants treated with dacomitinib with at least one measured plasma concentration.

Mean Ctrough values of dacomitinib observed from Cycle 2 through 5, Day 1 for dose compliant participants.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=317 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Trough Concentrations (Ctrough) of Dacomitinib. Cycle (C) 2 Day (D) 1 (n=317)	61.0102 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 77	—
Trough Concentrations (Ctrough) of Dacomitinib. C3D1 (n=175)	46.5229 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 97	—
Trough Concentrations (Ctrough) of Dacomitinib. C4D1 (n=131)	44.2708 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 86	—
Trough Concentrations (Ctrough) of Dacomitinib. C5D1 (n=95)	38.0307 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 83	—

SECONDARY outcome

Timeframe: Baseline up to Cycle 5 Day 1

Population: Participants treated with dacomitinib with at least one measured plasma concentration.

Mean Ctrough values of PF-05199265 observed from Cycle 2 through 5, Day 1 for dose compliant participants.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=323 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Trough Concentrations (Ctrough) of PF-05199265. Cycle (C) 2 Day (D) 1 (n=323)	6.3695 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 129	—
Trough Concentrations (Ctrough) of PF-05199265. C3D1 (n=179)	5.8706 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 123	—
Trough Concentrations (Ctrough) of PF-05199265. C4D1 (n=136)	6.4380 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 116	—
Trough Concentrations (Ctrough) of PF-05199265. C5D1 (n=100)	6.5353 Trough Plasma Concentration (ng/mL) Geometric Coefficient of Variation 118	—

SECONDARY outcome

Timeframe: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal.

Population: The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

TTD defined as the time from first dose (baseline) to the first time a patient's score in pain, dyspnea, fatigue or cough from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-LC13) increased by ≥10 points. A ≥10 point increase in score had to be maintained for ≥2 consecutive cycles for the symptom to be considered deteriorated. Participants were censored at the last time when they completed an assessment for pain, dyspnea, fatigue or cough if they had not deteriorated. A 10 point or higher change in the score is perceived by participants as clinically significant.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=421 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=424 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough Patient Reported Disease Symptoms.	1.0 Months Interval 1.0 to 1.9	1.0 Months Interval 0.9 to 1.4

SECONDARY outcome

Timeframe: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Population: The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a better level of quality of life. Overall scores present the mean score for that scale from all time-point data.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=421 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=424 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) QLQ-C30 Global QoL	56.4068 Units on a scale. Interval 54.631 to 58.183	58.3425 Units on a scale. Interval 56.554 to 60.131
Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) QLQ-C30 Cognitive Functioning	83.8980 Units on a scale. Interval 82.275 to 85.521	83.0913 Units on a scale. Interval 81.461 to 84.722
Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) QLQ-C30 Emotional Functioning	79.1982 Units on a scale. Interval 77.39 to 81.007	78.4682 Units on a scale. Interval 76.658 to 80.279
Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) QLQ-C30 Physical Functioning	75.2138 Units on a scale. Interval 73.25 to 77.21	73.6849 Units on a scale. Interval 71.719 to 75.651
Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) QLQ-C30 Role Functioning	69.3252 Units on a scale. Interval 66.771 to 71.879	68.1033 Units on a scale. Interval 65.553 to 70.653
Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) QLQ-C30 Social Functioning	74.7868 Units on a scale. Interval 72.371 to 77.203	76.2839 Units on a scale. Interval 73.864 to 78.703

SECONDARY outcome

Timeframe: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Population: The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=421 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=424 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Appetite loss	28.5960 Units on a scale. Interval 25.841 to 31.351	27.3109 Units on a scale. Interval 24.532 to 30.09
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Constipation	8.2496 Units on a scale. Interval 6.392 to 10.108	14.1726 Units on a scale. Interval 12.299 to 16.046
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Diarrhea	38.8641 Units on a scale. Interval 36.303 to 41.425	18.6077 Units on a scale. Interval 16.017 to 21.198
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Dysponea	28.3313 Units on a scale. Interval 25.736 to 30.927	32.8812 Units on a scale. Interval 30.282 to 35.48
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Fatigue	35.0885 Units on a scale. Interval 32.848 to 37.329	36.7469 Units on a scale. Interval 34.494 to 38.999
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Financial Difficulties	20.0597 Units on a scale. Interval 17.76 to 22.36	20.0597 Units on a scale. Interval 17.76 to 22.36
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Insomnia	19.7903 Units on a scale. Interval 17.413 to 22.168	24.6615 Units on a scale. Interval 22.276 to 27.046
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Nausea and Vomiting	9.1438 Units on a scale. Interval 7.759 to 10.528	9.6362 Units on a scale. Interval 8.208 to 11.065
Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30. QLQ-C30 Pain	25.1850 Units on a scale. Interval 22.867 to 27.503	24.8754 Units on a scale. Interval 22.551 to 27.2

SECONDARY outcome

Timeframe: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Population: The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

The QLQ-LC13 included questions specific to the disease associated symptoms (dyspnea, cough, haemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy, and alopecia), and analgesic use of lung cancer patients. Scores range from 0-100 and a higher score indicates greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data.

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=421 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=424 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Trouble Swallowing	10.1934 Units on a scale. Interval 8.36 to 12.027	7.5553 Units on a scale. Interval 5.711 to 9.4
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Coughing	28.3790 Units on a scale. Interval 26.037 to 30.721	32.6294 Units on a scale. Interval 30.272 to 34.986
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Haemoptysis	3.4751 Units on a scale. Interval 2.118 to 4.832	4.5515 Units on a scale. Interval 2.615 to 6.488
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Sore Mouth	20.4054 Units on a scale. Interval 18.115 to 22.696	11.0509 Units on a scale. Interval 8.731 to 13.371
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Shortness of Breath	27.1651 Units on a scale. Interval 25.161 to 29.169	28.3413 Units on a scale. Interval 26.346 to 30.337
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Peripheral Neuropathy	19.4905 Units on a scale. Interval 17.222 to 21.759	20.1284 Units on a scale. Interval 17.85 to 22.407
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Alopecia	14.8327 Units on a scale. Interval 11.848 to 17.818	16.1963 Units on a scale. Interval 13.22 to 19.173
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Pain in Chest	16.4268 Units on a scale. Interval 14.335 to 18.518	17.6430 Units on a scale. Interval 15.541 to 19.745
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Pain in Arm or Shoulder	15.9840 Units on a scale. Interval 13.864 to 18.104	17.1315 Units on a scale. Interval 14.989 to 19.274
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Pain in other Parts	21.5437 Units on a scale. Interval 19.02 to 24.067	22.6124 Units on a scale. Interval 20.06 to 25.165
Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13. QLQ-LC13 Any Med for Pain	61.8437 Units on a scale. Interval 58.169 to 65.519	61.8115 Units on a scale. Interval 58.038 to 65.585

SECONDARY outcome

Timeframe: Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Population: The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

The EQ-5D is a validated and reliable self-report preference-based measure developed by the EuroQoL Group to assess health-related quality of life. It consists of the EQ-5D descriptive system and a visual analogue scale-the EQ VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no health problems," "moderate health problems," and "extreme health problems." The EQ VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).

Outcome measures

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=421 Participants Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=424 Participants Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Mean and Difference in Mean of the EuroQoL-5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) Score	65.1908 Units on a scale. Interval 63.519 to 66.863	65.5794 Units on a scale. Interval 63.908 to 67.25

Adverse Events

Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)

Serious events: 178 serious events

Other events: 424 other events

Deaths: 0 deaths

Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)

Serious events: 169 serious events

Other events: 417 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=436 participants at risk Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=436 participants at risk Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Blood and lymphatic system disorders Anaemia	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Coagulopathy	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile neutropenia	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Splenic infarction	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute coronary syndrome	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute myocardial infarction	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac arrest	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac tamponade	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial infarction	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Pericardial effusion	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Supraventricular tachycardia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hypothyroidism	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Retinal artery embolism	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Retinal detachment	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	4.6% 20/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.6% 7/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dysphagia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric ulcer	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haematemesis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Inguinal hernia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Melaena	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis acute	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pneumoperitoneum	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Retroperitoneal haemorrhage	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Axillary pain	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Catheter site pain	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Condition aggravated	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Death	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Disease progression	12.2% 53/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.0% 48/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Drug interaction	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Mucosal inflammation	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pain	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Performance status decreased	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholangitis acute	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic failure	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hyperbilirubinaemia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Abdominal sepsis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Acne pustular	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchopneumonia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Diverticulitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infectious pleural effusion	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lobar pneumonia	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lung abscess	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lung infection	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Oral candidiasis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	2.8% 12/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.4% 15/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia pseudomonal	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Rash pustular	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Respiratory tract infection	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Rhinitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Septic shock	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Staphylococcal sepsis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Viral infection	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femoral neck fracture	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Incisional hernia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Radiation oesophagitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Radius fracture	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Rib fracture	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspiration bronchial	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood calcium decreased	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood creatine phosphokinase increased	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations C-reactive protein increased	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Haemoglobin decreased	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Hepatic enzyme increased	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations International normalised ratio increased	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Platelet count decreased	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Cachexia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.4% 6/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Failure to thrive	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypercalcaemia	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Malnutrition	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Chondrocalcinosis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma metastatic	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral infarction	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral ischaemia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebrovascular accident	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hemiparesis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypotonia	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Paraplegia	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Seizure	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Syncope	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Transient ischaemic attack	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Delirium	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Mental status changes	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Acute kidney injury	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Calculus ureteric	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Haematuria	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Prerenal failure	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal impairment	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Urinary retention	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.69% 3/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.92% 4/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Drug eruption	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Erythema multiforme	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Exfoliative rash	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash generalised	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Hospitalisation	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Internal fixation of fracture	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Deep vein thrombosis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Embolism	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypovolaemic shock	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Peripheral artery thrombosis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Phlebitis	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Venous thrombosis	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.23% 1/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo) n=436 participants at risk Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo) n=436 participants at risk Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.6% 7/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	8.0% 35/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.9% 43/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Dry eye	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.6% 20/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Cheilitis	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	9.9% 43/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.5% 59/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	73.9% 322/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	49.8% 217/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dry mouth	3.2% 14/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	4.6% 20/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dysphagia	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 11/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	20.6% 90/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	18.6% 81/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	18.6% 81/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.9% 52/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	16.3% 71/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	16.1% 70/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	14.9% 65/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.5% 59/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 36/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	17.9% 78/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	21.1% 92/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 11/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Malaise	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.6% 7/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Mucosal inflammation	15.4% 67/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.4% 28/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Oedema peripheral	3.9% 17/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 29/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pain	2.8% 12/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	9.4% 41/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 36/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Xerosis	3.2% 14/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.6% 7/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Conjunctivitis	6.7% 29/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.2% 14/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cystitis	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.6% 20/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Paronychia	21.6% 94/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.1% 44/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Rash pustular	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Respiratory tract infection	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 12/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	4.1% 18/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.0% 22/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood bilirubin increased	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 11/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	3.9% 17/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Weight decreased	14.7% 64/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.7% 38/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	31.7% 138/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	27.3% 119/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	6.0% 26/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.2% 14/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoalbuminaemia	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	6.4% 28/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypomagnesaemia	5.0% 22/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	3.4% 15/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	8.0% 35/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.9% 30/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	3.4% 15/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 11/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.6% 20/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.46% 2/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	6.0% 26/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.0% 26/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	3.9% 17/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 25/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dysgeusia	7.8% 34/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.0% 22/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	4.1% 18/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.6% 20/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	3.7% 16/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	1.6% 7/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	3.2% 14/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 25/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	12.4% 54/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	16.7% 73/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dysphonia	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.4% 76/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	18.6% 81/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.5% 37/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.3% 23/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.3% 23/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.5% 37/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Nasal inflammation	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.8% 8/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.5% 11/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.1% 5/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Productive cough	3.0% 13/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 12/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.1% 9/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	1.6% 7/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Acne	5.3% 23/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Alopecia	3.2% 14/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.1% 18/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dermatitis acneiform	18.6% 81/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	20.2% 88/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dry skin	19.7% 86/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	19.3% 84/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Erythema	4.1% 18/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.8% 21/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	11.2% 49/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	12.4% 54/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	50.0% 218/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	46.6% 203/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	4.1% 18/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 12/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Skin exfoliation	3.4% 15/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.3% 10/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Skin fissures	5.5% 24/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	4.4% 19/436 • AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks. The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

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