Pulmonary Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Pulmonary Hypertension, PH, PAH, Bardoxolone methyl, 6-minute walk distance, CDDO-ME, RTA 402, LARIAT, CATALYST, RANGER
Brief summary
This extended access study will assess the long-term safety and tolerability of bardoxolone methyl in qualified patients with pulmonary hypertension (PH) who previously participated in controlled clinical studies with bardoxolone methyl.
Detailed description
This extended access study will assess the long-term safety and tolerability of bardoxolone methyl in qualified patients with pulmonary hypertension (PH) who previously participated in controlled clinical studies with bardoxolone methyl. Qualified patients will receive 10 mg of bardoxolone methyl once daily until the drug is available through commercial channels or until patient withdrawal, whichever is sooner. Dose de-escalation (down to 5 mg) is permitted during the study, if indicated clinically.
Interventions
Capsules of Bardoxolone methyl
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Treatment-compliant patients who are participating in qualifying ongoing studies and have completed required End-of-Treatment and/or Follow-up visits in a prior clinical study with bardoxolone methyl
Exclusion criteria
* Participation in other investigational clinical studies involving interventional products being tested or used in a way different from the approved form or when used for an unapproved indication; * Patients who have an ongoing SAE from a clinical study that is assessed by the investigator as related to bardoxolone methyl; * Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) while taking study drug; * Women who are pregnant or breastfeeding; * Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason; * Known hypersensitivity to any component of the study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study | From time of first dose until the final visit, up to 172 weeks | 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. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czechia, Germany, Israel, Japan, Mexico, Netherlands, Philippines, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 261 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Reasons | 3 |
| Overall Study | Adverse Event | 19 |
| Overall Study | Death | 14 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Protocol specified withdrawal criterion | 1 |
| Overall Study | Study terminated by sponsor | 194 |
| Overall Study | Withdrawal by Subject | 26 |
Baseline characteristics
| Characteristic | Bardoxolone Methyl |
|---|---|
| Age, Continuous | 56.7 years STANDARD_DEVIATION 12.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 204 Participants |
| Region of Enrollment Argentina | 23 participants |
| Region of Enrollment Australia | 13 participants |
| Region of Enrollment Belgium | 3 participants |
| Region of Enrollment Brazil | 4 participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment Czechia | 3 participants |
| Region of Enrollment Germany | 4 participants |
| Region of Enrollment Israel | 3 participants |
| Region of Enrollment Japan | 12 participants |
| Region of Enrollment Mexico | 11 participants |
| Region of Enrollment Netherlands | 2 participants |
| Region of Enrollment Philippines | 5 participants |
| Region of Enrollment Spain | 8 participants |
| Region of Enrollment United Kingdom | 3 participants |
| Region of Enrollment United States | 161 participants |
| Sex: Female, Male Female | 221 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 261 |
| other Total, other adverse events | 198 / 261 |
| serious Total, serious adverse events | 106 / 261 |
Outcome results
Primary
Long Term Safety as Measured by Incidence and Severity of Adverse Events During the Duration of the Study
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.
Time frame: 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)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bardoxolone Methyl | 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 |
| Bardoxolone Methyl | 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 |
| Bardoxolone Methyl | 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 |
| Bardoxolone Methyl | 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 |
| Bardoxolone Methyl | 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 |
| Bardoxolone Methyl | 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 |