Trial Outcomes & Findings for A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® (Kronos) (NCT NCT02497001)

NCT ID: NCT02497001

Last Updated: 2020-12-24

Results Overview

FEV1 AUC0-4 (L) for The Efficacy Estimand (Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4) AUC was normalized for length of follow up (e.g. typically 4 hours)).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1902 participants
• Primary outcome timeframe: at Week 24
• Results posted on: 2020-12-24

Participant Flow

This study was conducted at 208 sites in four countries, from August 2015 until January 2018. The entire study period could take up to a maximum of 30 weeks.

Subjects were randomized in a 2:2:1:1 scheme.

Participant milestones

Measure	BGF MDI 320/14.4/9.6 ug Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug	BFF MDI 320/9.6 ug Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug	Symbicort TBH 400/12 ug Symbicort Turbuhaler 400/12 ug
Overall Study STARTED	640	627	316	319
Overall Study COMPLETED	566	524	266	278
Overall Study NOT COMPLETED	74	103	50	41

Reasons for withdrawal

Measure	BGF MDI 320/14.4/9.6 ug Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug	BFF MDI 320/9.6 ug Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug	Symbicort TBH 400/12 ug Symbicort Turbuhaler 400/12 ug
Overall Study Lost to Follow-up	10	2	0	2
Overall Study Adverse Event	28	30	11	11
Overall Study Withdrawal by Subject	14	37	19	15
Overall Study Physician Decision	5	11	5	1
Overall Study subjects that were not treated	1	2	2	1
Overall Study Major Protocol Deviation	3	4	4	4
Overall Study Lack of Efficacy	10	16	6	6
Overall Study Protocol Violation	3	1	3	1

Baseline Characteristics

mITT

Baseline characteristics by cohort

Measure	BGF MDI 320/14.4/9.6 ug n=639 Participants Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=625 Participants Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug	BFF MDI 320/9.6 ug n=314 Participants Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug	Symbicort TBH 400/12 ug n=318 Participants Symbicort Turbuhaler 400/12 ug	Total n=1896 Participants Total of all reporting groups
Age, Continuous	64.9 Years STANDARD_DEVIATION 7.8 • n=93 Participants • mITT	65.1 Years STANDARD_DEVIATION 7.7 • n=4 Participants • mITT	65.2 Years STANDARD_DEVIATION 7.2 • n=27 Participants • mITT	65.9 Years STANDARD_DEVIATION 7.7 • n=483 Participants • mITT	65.2 Years STANDARD_DEVIATION 7.7 • n=36 Participants • mITT
Sex: Female, Male Female	179 Participants n=93 Participants	195 Participants n=4 Participants	90 Participants n=27 Participants	82 Participants n=483 Participants	546 Participants n=36 Participants
Sex: Female, Male Male	460 Participants n=93 Participants	430 Participants n=4 Participants	224 Participants n=27 Participants	236 Participants n=483 Participants	1350 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=93 Participants • mITT	14 Participants n=4 Participants • mITT	7 Participants n=27 Participants • mITT	4 Participants n=483 Participants • mITT	41 Participants n=36 Participants • mITT
Ethnicity (NIH/OMB) Not Hispanic or Latino	623 Participants n=93 Participants • mITT	611 Participants n=4 Participants • mITT	305 Participants n=27 Participants • mITT	312 Participants n=483 Participants • mITT	1851 Participants n=36 Participants • mITT
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants • mITT	0 Participants n=4 Participants • mITT	2 Participants n=27 Participants • mITT	2 Participants n=483 Participants • mITT	4 Participants n=36 Participants • mITT
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants • mITT	0 Participants n=4 Participants • mITT	0 Participants n=27 Participants • mITT	0 Participants n=483 Participants • mITT	1 Participants n=36 Participants • mITT
Race (NIH/OMB) Asian	284 Participants n=93 Participants • mITT	285 Participants n=4 Participants • mITT	142 Participants n=27 Participants • mITT	141 Participants n=483 Participants • mITT	852 Participants n=36 Participants • mITT
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants • mITT	1 Participants n=4 Participants • mITT	0 Participants n=27 Participants • mITT	0 Participants n=483 Participants • mITT	1 Participants n=36 Participants • mITT
Race (NIH/OMB) Black or African American	23 Participants n=93 Participants • mITT	38 Participants n=4 Participants • mITT	15 Participants n=27 Participants • mITT	14 Participants n=483 Participants • mITT	90 Participants n=36 Participants • mITT
Race (NIH/OMB) White	329 Participants n=93 Participants • mITT	301 Participants n=4 Participants • mITT	157 Participants n=27 Participants • mITT	163 Participants n=483 Participants • mITT	950 Participants n=36 Participants • mITT
Race (NIH/OMB) More than one race	0 Participants n=93 Participants • mITT	0 Participants n=4 Participants • mITT	0 Participants n=27 Participants • mITT	0 Participants n=483 Participants • mITT	0 Participants n=36 Participants • mITT
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants • mITT	0 Participants n=4 Participants • mITT	0 Participants n=27 Participants • mITT	0 Participants n=483 Participants • mITT	2 Participants n=36 Participants • mITT

PRIMARY outcome

Timeframe: at Week 24

Population: mITT population total numbers may vary based on predefined subject exclusions prior to study unblinding

FEV1 AUC0-4 (L) for The Efficacy Estimand (Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4) AUC was normalized for length of follow up (e.g. typically 4 hours)).

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=436 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=403 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=201 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=211 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
FEV1 AUC0-4	0.292 Liters Interval 0.271 to 0.314	0.288 Liters Interval 0.266 to 0.31	0.177 Liters Interval 0.146 to 0.207	0.189 Liters Interval 0.16 to 0.219

PRIMARY outcome

Timeframe: at Week 24

Population: mITT

Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=565 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=522 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=266 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=276 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Change From Baseline in Morning Pre-dose Trough FEV1	0.124 Liters Interval 0.108 to 0.14	0.111 Liters Interval 0.094 to 0.127	0.050 Liters Interval 0.027 to 0.072	0.062 Liters Interval 0.039 to 0.084

SECONDARY outcome

Timeframe: over 24 Weeks

Population: mITT

Morning Pre-Dose Trough FEV1 (L) for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=622 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=601 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=300 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=301 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Change From Baseline in Morning Pre-dose Trough FEV1	0.147 Liters Interval 0.134 to 0.159	0.125 Liters Interval 0.112 to 0.137	0.073 Liters Interval 0.055 to 0.091	0.088 Liters Interval 0.07 to 0.105

SECONDARY outcome

Timeframe: at Week 24

Population: mITT

Peak Change from Baseline in FEV1 (L) Within 4 Hours Post-Dose for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=436 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=403 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=201 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=211 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Peak Change From Baseline in FEV1 Within 4 Hours Post-dosing	0.370 Liters Interval 0.348 to 0.393	0.361 Liters Interval 0.338 to 0.384	0.253 Liters Interval 0.221 to 0.284	0.264 Liters Interval 0.233 to 0.295

SECONDARY outcome

Timeframe: over 24 weeks

Population: mITT

Rate of Moderate or Severe COPD Exacerbations for the Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=108 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=157 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=65 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=61 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Rate of Moderate or Severe COPD Exacerbations	0.46 Exacerbations Standard Error 0.05	0.95 Exacerbations Standard Error 0.09	0.56 Exacerbations Standard Error 0.08	0.55 Exacerbations Standard Error 0.08

SECONDARY outcome

Timeframe: at Week 24

Population: mITT

Change from BGF

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=625 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=314 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=318 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® Symbicort® Turbuhaler® (TBH) Inhalation Powder
Percentage of Subjects Achieving a Minimal Clinically Important Difference (MCID) of 4 Units or More in SGRQ Total Score (SGRQ Responders)	6.06 Percentage Interval 0.3 to 11.82	6.43 Percentage Interval -0.62 to 13.47	8.23 Percentage Interval 1.23 to 15.22	—

SECONDARY outcome

Timeframe: over 24 Weeks

Population: mITT

Change from Baseline in Mean Daily Number of Puffs of Rescue Ventolin HFA for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=141 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=155 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=269 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=233 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Change From Baseline in Average Daily Rescue Ventolin HFA Use	-1.3 Puffs Interval -1.6 to -1.1	-1.1 Puffs Interval -1.3 to -0.8	-1.1 Puffs Interval -1.5 to -0.8	-1.6 Puffs Interval -1.9 to -1.2

SECONDARY outcome

Timeframe: Day 1

Population: mITT

FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=429 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=417 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=220 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=210 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Time to Onset of Action on Day 1, 5 Minutes Post Dose	0.181 Liters Interval 0.169 to 0.192	0.194 Liters Interval 0.182 to 0.205	0.167 Liters Interval 0.152 to 0.182	0.163 Liters Interval 0.148 to 0.178

SECONDARY outcome

Timeframe: Day 1

Population: mITT

FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=484 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=470 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=238 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=238 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Time to Onset of Action on Day 1, 15 Minutes Post Dose	0.217 Liters Interval 0.205 to 0.23	0.230 Liters Interval 0.218 to 0.243	0.197 Liters Interval 0.18 to 0.213	0.190 Liters Interval 0.174 to 0.207

SECONDARY outcome

Timeframe: Day 1

Population: mITT

FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=490 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=474 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=242 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=238 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Time to Onset of Action on Day 1, 30 Minutes Post Dose	0.236 Liters Interval 0.223 to 0.249	0.255 Liters Interval 0.242 to 0.268	0.213 Liters Interval 0.195 to 0.23	0.208 Liters Interval 0.19 to 0.225

SECONDARY outcome

Timeframe: Day 1

Population: mITT

FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=497 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=481 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=244 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=245 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Time to Onset of Action on Day 1, 1 Hour Post Dose	0.268 Liters Interval 0.254 to 0.282	0.282 Liters Interval 0.268 to 0.296	0.228 Liters Interval 0.208 to 0.247	0.232 Liters Interval 0.213 to 0.251

SECONDARY outcome

Timeframe: Day 1

Population: mITT

FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=494 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=480 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=243 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=246 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Time to Onset of Action on Day 1, 2 Hours Post Dose	0.281 Liters Interval 0.266 to 0.295	0.292 Liters Interval 0.277 to 0.307	0.241 Liters Interval 0.22 to 0.261	0.244 Liters Interval 0.224 to 0.265

SECONDARY outcome

Timeframe: Day 1

Population: mITT

FEV1 (L) by Post-Dose Timepoint on Day 1 for The Efficacy Estimand

Outcome measures

Measure	BGF MDI 320/14.4/9.6 μg n=491 Participants Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (PT010, BGF metered dose inhaler \[MDI\])	GFF MDI (PT003) 14.4/9.6 μg n=477 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (PT003, GFF MDI)	BFF MDI (PT009) 320/9.6 μg n=243 Participants Budesonide and Formoterol Fumarate Inhalation Aerosol (PT009, BFF MDI)	Symbicort® n=244 Participants Symbicort® Turbuhaler® (TBH) Inhalation Powder
Time to Onset of Action on Day 1, 4 Hours Post Dose	0.276 Liters Interval 0.26 to 0.292	0.278 Liters Interval 0.262 to 0.294	0.234 Liters Interval 0.213 to 0.256	0.247 Liters Interval 0.225 to 0.268

Adverse Events

BGF MDI 320/14.4/9.6 ug

Serious events: 55 serious events

Other events: 126 other events

Deaths: 6 deaths

GFF MDI 14.4/9.6 ug

Serious events: 68 serious events

Other events: 84 other events

Deaths: 3 deaths

BFF MDI 320/9.6 ug

Serious events: 21 serious events

Other events: 59 other events

Deaths: 2 deaths

Symbicort TBH 400/12 ug

Serious events: 29 serious events

Other events: 55 other events

Deaths: 1 deaths

Serious adverse events

Measure	BGF MDI 320/14.4/9.6 ug n=639 participants at risk Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=625 participants at risk Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug	BFF MDI 320/9.6 ug n=314 participants at risk Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug	Symbicort TBH 400/12 ug n=318 participants at risk Symbicort Turbuhaler 400/12 ug
Cardiac disorders Acute coronary syndrome	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.7% 17/639 • Number of events 17 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.1% 32/625 • Number of events 41 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	2.5% 8/314 • Number of events 8 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	4.1% 13/318 • Number of events 16 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.63% 4/639 • Number of events 4 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.31% 2/639 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Pneumonia	1.3% 8/639 • Number of events 8 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.96% 6/625 • Number of events 6 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Sepsis	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Influenza	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Appendicitis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Cellulitis	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Clostridium difficile infection	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Dengue ferver	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Device related infection	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Diverticulitits	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Gastritis viral	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Gastroenteritis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Herpes zoster	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Lung infection	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Lymphangitis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Meningitis viral	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Osteomyelitis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Pneumonia bacterial	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Pulmonary tuberculosis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Pyelonephritis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Pyelonephritis acute	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Urinary tract infection	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Acute myocardial infarction	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 2/625 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Coronary artery disease	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Atrial fibrilation	0.31% 2/639 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Angina unstable	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Atrioventricular block complete	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Cardiac failure chronic	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Cardiac failure tamponade	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Coronary artery occlusion	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Cardiac disorders Myocardial ischaemia	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukemia	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain cancer metastatic	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer metastatic	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of thymus	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metasteses of liver	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metasteses to lung	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papilloma	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer metastatic	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Urethral cancer	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Carotid artery stenosis	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Syncope	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Central nervous system lesion	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Cerebral infarction	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Cerebral ischeamia	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Cerebrovascular insufficiency	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Migraine	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Siezure	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 2/625 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Anal fistula	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Colitis ulcerative	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders gastrointestinal haemorrhage	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Intestinal polyp	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Large intestinal polyp	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Injury, poisoning and procedural complications Hip fracture	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Injury, poisoning and procedural complications Respiratory fume inhalation disorder	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Injury, poisoning and procedural complications Road traffic accident6	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.31% 2/639 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.16% 1/639 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
General disorders Non-cardiac chest pain	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
General disorders Death	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
General disorders Systemic inflammatory response syndrome	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Vascular disorders Arterial stenosis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Vascular disorders Hypertension	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Vascular disorders Iliac artery occlusion	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Vascular disorders Peripheral vascular disorder	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.32% 1/314 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Renal and urinary disorders Ureterolithiasis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Hepatobiliary disorders Cholangitis	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Hepatobiliary disorders Bile duct stone	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Hepatobiliary disorders Hepatic cyst	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Psychiatric disorders Delerium	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Psychiatric disorders Major depression	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Psychiatric disorders Suicide attempt	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.31% 1/318 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Blood and lymphatic system disorders Anaemia	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Eye disorders Cataract	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Investigations Electrocardiogram T wave inversion	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Reproductive system and breast disorders Prostatitis	0.16% 1/639 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/625 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Nervous system disorders Myelopathy	0.00% 0/639 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.16% 1/625 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/314 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	0.00% 0/318 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.

Other adverse events

Measure	BGF MDI 320/14.4/9.6 ug n=639 participants at risk Budesonide Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 320/14.4/9.6 ug	GFF MDI 14.4/9.6 ug n=625 participants at risk Glycopyrronium Formoterol Fumarate Metered Dose Inhalation 14.4/9.6 ug	BFF MDI 320/9.6 ug n=314 participants at risk Budesonide Formoterol Fumarate Metered Dose Inhalation 320/9.6 ug	Symbicort TBH 400/12 ug n=318 participants at risk Symbicort Turbuhaler 400/12 ug
Infections and infestations Nasopharyngitits	7.7% 49/639 • Number of events 61 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	6.6% 41/625 • Number of events 48 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	8.3% 26/314 • Number of events 30 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	9.4% 30/318 • Number of events 32 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Infections and infestations Upper Respiratory Infection	10.2% 65/639 • Number of events 77 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.9% 37/625 • Number of events 41 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.7% 18/314 • Number of events 18 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	6.9% 22/318 • Number of events 23 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.
Musculoskeletal and connective tissue disorders Muscle Spasms	3.3% 21/639 • Number of events 21 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	1.3% 8/625 • Number of events 9 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	5.4% 17/314 • Number of events 18 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.	1.9% 6/318 • Number of events 6 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call. Adverse Events were collected from the time subject was randomized. The Safety Population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study drug.

Additional Information

Pearl Therapeutics Inc.

Pearl Therapeutics Inc.

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER