Trial Outcomes & Findings for Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension RANGER (NCT NCT03068130)

NCT ID: NCT03068130

Last Updated: 2025-06-11

Results Overview

Severity was defined using the following definitions: Mild: Symptoms causing no or minimal interference with usual social and functional activities; Moderate: Symptoms causing greater than minimal interference with usual social and functional activities; Severe: Symptoms causing inability to perform usual social and functional activities.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 261 participants
• Primary outcome timeframe: From time of first dose until the final visit, up to 172 weeks
• Results posted on: 2025-06-11

Participant Flow

Participant milestones

Measure	Bardoxolone Methyl Participants who received bardoxolone methyl capsules (administered orally). Dosing started at 10 mg once daily (if enrolled under version 2.0, 2.1 \[UK\], 2.2 \[Germany\] of the protocol) or every other day (if enrolled under version 3.0, 3.1 \[UK\], 3.1 and 3.2 \[Germany\] of the protocol). For participants who began by dosing every other day, once daily dosing at 10 mg began at Week 4, unless contraindicated clinically. In Japan, participants began dosing at 5 mg once daily then dose-escalated to 10 mg at Week 4, unless contraindicated clinically.
Overall Study STARTED	261
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	261

Reasons for withdrawal

Measure	Bardoxolone Methyl Participants who received bardoxolone methyl capsules (administered orally). Dosing started at 10 mg once daily (if enrolled under version 2.0, 2.1 \[UK\], 2.2 \[Germany\] of the protocol) or every other day (if enrolled under version 3.0, 3.1 \[UK\], 3.1 and 3.2 \[Germany\] of the protocol). For participants who began by dosing every other day, once daily dosing at 10 mg began at Week 4, unless contraindicated clinically. In Japan, participants began dosing at 5 mg once daily then dose-escalated to 10 mg at Week 4, unless contraindicated clinically.
Overall Study Adverse Event	19
Overall Study Death	14
Overall Study Lost to Follow-up	4
Overall Study Withdrawal by Subject	26
Overall Study Administrative Reasons	3
Overall Study Protocol specified withdrawal criterion	1
Overall Study Study terminated by sponsor	194

Baseline Characteristics

Extended Access Program to Assess Long-term Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension RANGER

Baseline characteristics by cohort

Measure	Bardoxolone Methyl n=261 Participants Participants who received bardoxolone methyl capsules (administered orally). Dosing started at 10 mg once daily (if enrolled under version 2.0, 2.1 \[UK\], 2.2 \[Germany\] of the protocol) or every other day (if enrolled under version 3.0, 3.1 \[UK\], 3.1 and 3.2 \[Germany\] of the protocol). For participants who began by dosing every other day, once daily dosing at 10 mg began at Week 4, unless contraindicated clinically. In Japan, participants began dosing at 5 mg once daily then dose-escalated to 10 mg at Week 4, unless contraindicated clinically.
Age, Continuous	56.7 years STANDARD_DEVIATION 12.79 • n=5 Participants
Sex: Female, Male Female	221 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	200 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	22 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	30 Participants n=5 Participants
Race (NIH/OMB) White	204 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Region of Enrollment Argentina	23 participants n=5 Participants
Region of Enrollment United States	161 participants n=5 Participants
Region of Enrollment Czechia	3 participants n=5 Participants
Region of Enrollment Japan	12 participants n=5 Participants
Region of Enrollment Philippines	5 participants n=5 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants
Region of Enrollment Spain	8 participants n=5 Participants
Region of Enrollment Canada	6 participants n=5 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants
Region of Enrollment Belgium	3 participants n=5 Participants
Region of Enrollment Brazil	4 participants n=5 Participants
Region of Enrollment Mexico	11 participants n=5 Participants
Region of Enrollment Israel	3 participants n=5 Participants
Region of Enrollment Australia	13 participants n=5 Participants
Region of Enrollment Germany	4 participants n=5 Participants

PRIMARY outcome

Timeframe: From time of first dose until the final visit, up to 172 weeks

Population: Safety population (all patients who received at least 1 dose of bardoxolone methyl)

Severity was defined using the following definitions: Mild: Symptoms causing no or minimal interference with usual social and functional activities; Moderate: Symptoms causing greater than minimal interference with usual social and functional activities; Severe: Symptoms causing inability to perform usual social and functional activities.

Outcome measures

Measure	Bardoxolone Methyl n=261 Participants Participants who received bardoxolone methyl capsules (administered orally). Dosing started at 10 mg once daily (if enrolled under version 2.0, 2.1 \[UK\], 2.2 \[Germany\] of the protocol) or every other day (if enrolled under version 3.0, 3.1 \[UK\], 3.1 and 3.2 \[Germany\] of the protocol). For participants who began by dosing every other day, once daily dosing at 10 mg began at Week 4, unless contraindicated clinically. In Japan, participants began dosing at 5 mg once daily then dose-escalated to 10 mg at Week 4, unless contraindicated clinically.
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study Number and percent of participants with a serious adverse event	106 Participants
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study Number and percent of participants with worst adverse event severity of mild	42 Participants
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study Number and percent of participants with worst adverse event severity of moderate	96 Participants
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study Number and percent of participants with worst adverse event severity of severe	94 Participants
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study Number and percent of participants with at least one adverse event	232 Participants
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study Number and percent of participants with a related adverse event	89 Participants

Adverse Events

Bardoxolone Methyl

Serious events: 106 serious events

Other events: 198 other events

Deaths: 17 deaths

Serious adverse events

Measure	Bardoxolone Methyl n=261 participants at risk Participants who received bardoxolone methyl capsules (administered orally). Dosing started at 10 mg once daily (if enrolled under version 2.0, 2.1 \[UK\], 2.2 \[Germany\] of the protocol) or every other day (if enrolled under version 3.0, 3.1 \[UK\], 3.1 and 3.2 \[Germany\] of the protocol). For participants who began by dosing every other day, once daily dosing at 10 mg began at Week 4, unless contraindicated clinically. In Japan, participants began dosing at 5 mg once daily then dose-escalated to 10 mg at Week 4, unless contraindicated clinically.
Ear and labyrinth disorders Vertigo	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Ascites	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Colitis ischaemic	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Dental cyst	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Duodenitis	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Dysphagia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Faecaloma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Gastritis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.1% 3/261 • Number of events 4 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Haemorrhoids thrombosed	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Intestinal obstruction	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Mallory-Weiss syndrome	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Oesophageal motility disorder	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Oesophageal stenosis	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Small intestinal obstruction	0.77% 2/261 • Number of events 4 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Vomiting	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Chest pain	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Complication associated with device	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Device related thrombosis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Multiple organ dysfunction syndrome	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Non-cardiac chest pain	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Oedema peripheral	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Hepatobiliary disorders Cholelithiasis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Appendicitis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Atypical pneumonia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Bacteraemia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Bursitis infective	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Cellulitis	1.5% 4/261 • Number of events 4 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Cellulitis staphylococcal	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Clostridium difficile infection	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Diarrhoea infectious	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Ecthyma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Haemophilus infection	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Herpes zoster	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Infectious colitis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Influenza	1.5% 4/261 • Number of events 4 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Lower respiratory tract infection	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Meningitis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Pneumonia	5.0% 13/261 • Number of events 13 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Pneumonia staphylococcal	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Respiratory tract infection	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Respiratory tract infection viral	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Sepsis	1.1% 3/261 • Number of events 4 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Septic shock	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Upper respiratory tract infection	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Urinary tract infection	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Accidental overdose	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Drug administration error	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Environmental exposure	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Eschar	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Joint injury	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Laceration	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Spinal compression fracture	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Investigations Norovirus test positive	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Investigations Weight decreased	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Decreased appetite	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Dehydration	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Fluid overload	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Hypoglycaemia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Hypomagnesaemia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Malnutrition	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Bursitis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Costochondritis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Myalgia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Scleroderma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Spinal deformity	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland cancer	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Blood and lymphatic system disorders Agranulocytosis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Blood and lymphatic system disorders Anaemia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Blood and lymphatic system disorders Iron deficiency anaemia	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Acute myocardial infarction	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Angina unstable	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Arteriosclerosis coronary artery	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Atrial fibrillation	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Atrial flutter	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Cardiac failure	1.5% 4/261 • Number of events 5 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Cardiac failure acute	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Cardiac failure congestive	0.77% 2/261 • Number of events 3 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Cardio-respiratory arrest	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Cardiogenic shock	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Coronary artery occlusion	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Dilatation ventricular	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Left ventricular failure	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Myocardial infarction	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Palpitations	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Pericardial effusion	1.1% 3/261 • Number of events 3 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Pericarditis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Right ventricular dysfunction	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Right ventricular failure	2.7% 7/261 • Number of events 10 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Cardiac disorders Systolic dysfunction	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Cerebellar artery thrombosis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Embolic stroke	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Headache	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Hepatic encephalopathy	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Lateral medullary syndrome	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Lumbar radiculopathy	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Metabolic encephalopathy	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Paraesthesia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Presyncope	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Spinal epidural haematoma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Subarachnoid haemorrhage	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Syncope	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Vasculitis cerebral	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Renal and urinary disorders Acute kidney injury	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Renal and urinary disorders Nephrolithiasis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Renal and urinary disorders Urinary retention	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Reproductive system and breast disorders Menometrorrhagia	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Reproductive system and breast disorders Ovarian cyst ruptured	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.5% 4/261 • Number of events 5 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Asthma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.38% 1/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.77% 2/261 • Number of events 2 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.1% 3/261 • Number of events 4 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.77% 2/261 • Number of events 3 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	5.0% 13/261 • Number of events 16 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.9% 5/261 • Number of events 6 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 3/261 • Number of events 3 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Vascular disorders Haematoma	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Vascular disorders Shock	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Vascular disorders Thrombophlebitis	0.38% 1/261 • Number of events 1 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.

Other adverse events

Measure	Bardoxolone Methyl n=261 participants at risk Participants who received bardoxolone methyl capsules (administered orally). Dosing started at 10 mg once daily (if enrolled under version 2.0, 2.1 \[UK\], 2.2 \[Germany\] of the protocol) or every other day (if enrolled under version 3.0, 3.1 \[UK\], 3.1 and 3.2 \[Germany\] of the protocol). For participants who began by dosing every other day, once daily dosing at 10 mg began at Week 4, unless contraindicated clinically. In Japan, participants began dosing at 5 mg once daily then dose-escalated to 10 mg at Week 4, unless contraindicated clinically.
Cardiac disorders Palpitations	4.6% 12/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Abdominal pain	3.8% 10/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Constipation	4.2% 11/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Diarrhoea	15.7% 41/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.0% 13/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Nausea	11.9% 31/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Gastrointestinal disorders Vomiting	4.6% 12/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Asthenia	2.3% 6/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Fatigue	7.3% 19/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Non-cardiac chest pain	3.8% 10/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Oedema peripheral	6.1% 16/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
General disorders Pyrexia	3.1% 8/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Bronchitis	8.0% 21/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Cellulitis	3.1% 8/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Conjunctivitis	3.8% 10/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Herpes zoster	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Influenza	5.4% 14/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Lower respiratory tract infection	3.1% 8/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Nasopharyngitis	5.0% 13/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Pneumonia	4.2% 11/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Respiratory tract infection	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Sinusitis	8.4% 22/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Upper respiratory tract infection	19.5% 51/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Infections and infestations Urinary tract infection	11.5% 30/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Injury, poisoning and procedural complications Arthropod bite	2.3% 6/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Investigations Brain natriuretic peptide increased	2.3% 6/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Investigations N-terminal prohormone brain natriuretic peptide increased	8.0% 21/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Investigations Weight decreased	6.1% 16/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Decreased appetite	5.7% 15/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Hypokalaemia	5.0% 13/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Hypomagnesaemia	2.7% 7/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Metabolism and nutrition disorders Vitamin D deficiency	2.3% 6/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Arthralgia	5.0% 13/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Back pain	5.0% 13/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Muscle spasms	12.6% 33/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Myalgia	5.0% 13/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Neck pain	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Pain in extremity	6.5% 17/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Musculoskeletal and connective tissue disorders Pain in jaw	2.7% 7/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Dizziness	8.4% 22/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Headache	10.0% 26/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Nervous system disorders Syncope	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Psychiatric disorders Insomnia	3.1% 8/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Cough	9.6% 25/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.6% 25/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.7% 7/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.3% 6/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.1% 8/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	3.4% 9/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	2.7% 7/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Skin and subcutaneous tissue disorders Rash	2.7% 7/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Skin and subcutaneous tissue disorders Skin ulcer	2.7% 7/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Blood and lymphatic system disorders Iron deficiency anaemia	5.4% 14/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.
Vascular disorders Hypotension	4.6% 12/261 • The time from the date of a participant's first dose to his or her last participation or event date, a maximum of 172 weeks All AEs and SAEs from the time of administration of the first dose until the final visit were to be reported. AEs and SAEs that occurred within 30 days after the last dose were considered treatment emergent. For SAEs, the investigator was to follow the patient until the SAE subsided or until the condition became chronic in nature, stabilized (in the case of persistent impairment), or the patient died.

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: clinicaltrials@biogen.com

Results disclosure agreements

• Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER