Trial Outcomes & Findings for An Extended Access Program for Bardoxolone Methyl in Patients With CKD (EAGLE) (NCT NCT03749447)

Last Updated: 2025-06-03

Results Overview

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or is a medically important event. AEs and SAEs that occurred within 30 days after the last dose were considered treatment-emergent. The study follow-up assessment was collected within 14 to 35 days after the last dose.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

270 participants

Primary outcome timeframe

From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years)

Results posted on

2025-06-03

Participant Flow

Participants were enrolled at the investigative sites in the United States, Australia, Japan, Spain, Puerto Rico and France from 08 March 2019 to 23 August 2023.

A total of 270 eligible participants who participated in the previous qualifying studies i.e., 402-C-1603 (NCT03019185) and 402-C-1808 (NCT03918447) of bardoxolone methyl were enrolled in this study. Data was summarized as per the treatment received in the previous qualifying studies.

Participant milestones

Participant milestones
Measure	Prior Placebo to Bardoxolone Methyl Participants who received placebo in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, once daily (QD) at a starting dose of 5 milligrams (mg), followed by dose- escalation to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility urine albumin to creatinine ratio (UACR) \>300 milligrams per gram (mg/g), the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.	Prior Bardoxolone Methyl to Bardoxolone Methyl Participants who received bardoxolone methyl in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose-escalated to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.
Overall Study STARTED	143	127
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	143	127

Reasons for withdrawal

Reasons for withdrawal
Measure	Prior Placebo to Bardoxolone Methyl Participants who received placebo in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, once daily (QD) at a starting dose of 5 milligrams (mg), followed by dose- escalation to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility urine albumin to creatinine ratio (UACR) \>300 milligrams per gram (mg/g), the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.	Prior Bardoxolone Methyl to Bardoxolone Methyl Participants who received bardoxolone methyl in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose-escalated to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.
Overall Study Adverse Event	11	3
Overall Study Death	1	1
Overall Study Lost to Follow-up	2	2
Overall Study Reason Not Specified	0	3
Overall Study Physician Decision	4	3
Overall Study Protocol-Specified Withdrawal Criteria Met	1	3
Overall Study Study Terminated By Sponsor	112	105
Overall Study Withdrawal by Subject	12	6
Overall Study Non-compliance With Study Drug	0	1

Baseline Characteristics

An Extended Access Program for Bardoxolone Methyl in Patients With CKD (EAGLE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prior Placebo to Bardoxolone Methyl n=143 Participants Participants who received placebo in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose- escalation to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.	Prior Bardoxolone Methyl to Bardoxolone Methyl n=127 Participants Participants who received bardoxolone methyl in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose-escalated to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.	Total n=270 Participants Total of all reporting groups
Age, Continuous	48.8 years STANDARD_DEVIATION 13.26 • n=5 Participants	48.3 years STANDARD_DEVIATION 13.82 • n=7 Participants	48.6 years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	78 Participants n=7 Participants	166 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	49 Participants n=7 Participants	104 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	112 Participants n=5 Participants	96 Participants n=7 Participants	208 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic/Latino	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Non-Hispanic/Latino	128 Participants n=5 Participants	115 Participants n=7 Participants	243 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years)

Population: The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.

Outcome measures

Outcome measures
Measure	Prior Placebo to Bardoxolone Methyl n=143 Participants Participants who received placebo in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose- escalation to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.	Prior Bardoxolone Methyl to Bardoxolone Methyl n=127 Participants Participants who received bardoxolone methyl in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose-escalated to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	128 Participants	105 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	12 Participants	20 Participants

Adverse Events

Prior Placebo to Bardoxolone Methyl

Serious events: 12 serious events

Other events: 127 other events

Deaths: 1 deaths

Prior Bardoxolone Methyl to Bardoxolone Methyl

Serious events: 20 serious events

Other events: 104 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for non-commercial 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

Measure	Prior Placebo to Bardoxolone Methyl n=143 participants at risk Participants who received placebo in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose- escalation to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.	Prior Bardoxolone Methyl to Bardoxolone Methyl n=127 participants at risk Participants who received bardoxolone methyl in the previous qualifying studies, 402-C-1603 (NCT03019185) or 402-C-1808 (NCT03918447), and received bardoxolone methyl in this study. Adult participants received bardoxolone methyl capsules, QD at a starting dose of 5 mg, followed by dose-escalated to 10 mg at Week 2 (Day 14 ± 3), and to 20 mg at Week 4 (Day 28 ± 3). Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 (Day 42 ± 3) until the end of the study. Participants under 18 years of age received bardoxolone methyl capsules at a starting dose of 5 mg every other day during the first week and QD during the second week of the study, followed by dose-escalation to 10 mg at Week 2 and to 20 mg at Week 4. Based on the eligibility UACR \>300 mg/g, the dose was increased to 30 mg starting from Week 6 until the end of the study.
Blood and lymphatic system disorders Anaemia	6.3% 9/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	4.7% 6/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Gastrointestinal disorders Nausea	8.4% 12/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	10.2% 13/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Gastrointestinal disorders Diarrhoea	11.2% 16/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	6.3% 8/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Gastrointestinal disorders Abdominal pain	6.3% 9/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	3.9% 5/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
General disorders Fatigue	9.8% 14/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	6.3% 8/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
General disorders Oedema peripheral	7.0% 10/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	8.7% 11/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
General disorders Pyrexia	4.9% 7/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	5.5% 7/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Infections and infestations Corona virus infection	15.4% 22/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	21.3% 27/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Infections and infestations Upper respiratory tract infection	8.4% 12/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	9.4% 12/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Infections and infestations Nasopharyngitis	3.5% 5/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	6.3% 8/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Infections and infestations Sinusitis	3.5% 5/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	6.3% 8/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Investigations Alanine aminotransferase increased	25.9% 37/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	6.3% 8/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Investigations Aspartate aminotransferase increased	16.8% 24/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	5.5% 7/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Investigations N-terminal prohormone brain natriuretic peptide increased	9.1% 13/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	8.7% 11/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Investigations Brain natriuretic peptide increased	7.7% 11/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	3.9% 5/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Investigations Gamma-glutamyltransferase increased	7.7% 11/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	0.00% 0/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Investigations Blood creatinine increased	2.1% 3/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	5.5% 7/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Metabolism and nutrition disorders Hyperkalaemia	7.0% 10/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	8.7% 11/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Metabolism and nutrition disorders Hypomagnesaemia	7.0% 10/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	3.1% 4/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Musculoskeletal and connective tissue disorders Muscle spasms	39.9% 57/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	35.4% 45/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Musculoskeletal and connective tissue disorders Back pain	8.4% 12/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	9.4% 12/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Musculoskeletal and connective tissue disorders Pain in extremity	2.8% 4/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	5.5% 7/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Nervous system disorders Headache	11.2% 16/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	7.1% 9/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Nervous system disorders Dizziness	3.5% 5/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	5.5% 7/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Respiratory, thoracic and mediastinal disorders Cough	2.8% 4/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	8.7% 11/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Vascular disorders Hypertension	5.6% 8/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	7.1% 9/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.
Infections and infestations Urinary tract infection	5.6% 8/143 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.	9.4% 12/127 • From the first dose of the study drug (baseline) up to the end of the study follow-up (up to 4.2 years) The safety population included all participants who had received at least 1 dose of bardoxolone methyl in the 402-C-1803 study.