Patient Exclusion Criteria. All patients with any of the following conditions or characteristics must be excluded from the study:
1. Prior exposure to bardoxolone methyl;
2. Ongoing chronic hemodialysis or peritoneal dialysis therapy;
3. Renal transplant recipient;
Patient Exclusion Criteria. Patients are excluded from participating in this study if 1 or more of the following criteria are met:
(a) The patient has been treated with intramuscular or intravenous (iv) pulse steroids (ie, 250 to 1000 mg iv total daily dose of methylprednisolone) within 4 weeks of the 1st dose of study drug. The use of intra-articular steroids may be allowed after consultation with the medical expert.
(b) The patient has received tacrolimus, cyclosporin A, or iv immunoglobulins (IVIG) within 3 months of the 1st dose of study drug.
(c) The patient has received cyclophosphamide within 6 months prior to the 1st dose of study drug.
(d) The patient has been treated for SLE with agents such as fusion proteins, therapeutic proteins, or monoclonal antibodies or antibody fragments, within 6 months of the 1st dose of study drug.
(e) The patient has received B-cell depleting agents such as rituximab, belimumab or epratuzumab within one year of the 1st dose of study drug and has not yet normalized the B- cell count (ie, CD20+ B-cell count is less than normal range and the absolute lymphocyte count [ALC] is less than normal range).
(f) The patient has New York Heart Association (NYHA) Class III or IV congestive heart failure.
(g) The patient has an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 (via Modification of Diet in Renal Disease [MDRD] equation).
(h) The patient has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value greater than 2 times the upper limit of the normal range (ULN) or a total bilirubin level greater than 1.5 times ULN.
(i) The patient has a planned immunization with a live or live attenuated vaccine within 3 months prior to administration of the 1st dose of study drug and for 3 months after administration of the last dose of study drug.
(j) The patient has any clinically significant abnormalities on ECG that are not related to SLE, as determined by the investigator. Patients with stable ECG changes without evidence of active cardiovascular disease may participate at the discretion of the investigator and medical monitor.
(k) The patient has an ongoing active systemic infection requiring treatment or a history of severe infection, such as hepatitis or pneumonia, in the 3 months prior to administration of the 1st dose of study drug. Less severe infections in the 3 months prior to administration of the 1st dose of study drug are permitted at the discretion of the investigator and medical monitor.
(l) The patie...
Patient Exclusion Criteria. A patient who meets any of the following criteria will be excluded from this study.
1. Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks of study drug administration that in the opinion of the Investigator might have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).
2. Previous treatment with SMT C1100/BMN 195 at any time.
3. Previous treatment with drisapersen (PRO051) within the last 6 months. Participation in any other DMD interventional clinical study within 12 weeks of study drug administration, or use of the shock training system or “STS,” or planned use during this study. Concurrent participation in an interventional clinical study or observational trial is not permitted.
4. Major change in physiotherapy regimen within the past 3 months or expected change over the study period.
5. Major surgery within 3 months of study drug administration or planned major surgery for any time during this study.
6. Presence of other clinically significant illness including significant cardiac, pulmonary, hepatic, renal, hematologic, immunologic, behavioral disease or malignancy.
7. Systemic use of any aminoglycoside antibiotic within 12 weeks of study drug administration or anticipated need for use of an aminoglycoside antibiotic or statin during the study.
8. CCI .
9. Must not require antiarrhythmic and/or antidiuretic therapy for heart failure. Patients are allowed to take other medication including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), β blockers or potassium, provided they have been on a stable dose for 24 weeks prior to study drug administration and the dose is expected to remain constant throughout the study.
Patient Exclusion Criteria. All patients with any of the following conditions or characteristics must be excluded from the study:
1. 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 within 30 days prior to Day 1;
2. Initiation of an exercise program for cardio-pulmonary rehabilitation within 90 days prior to Day 1 or planned initiation during the study;
3. Stopped receiving any PAH chronic therapy within 60 days prior to Day 1;
4. Received a dose of prednisone >20 mg/day (or equivalent dose if other corticosteroid) within 30 days prior to Day 1;
5. Received intravenous (iv) or subcutaneous (sc) prostacyclin/prostacyclin analogues within 90 days prior to Day 1;
6. Received intravenous inotropes within 30 days prior to Day 1;
7. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic BP > 100 mm Hg during Screening after a period of rest;
8. Has systolic BP < 90 mm Hg during Screening after a period of rest;
9. Has a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. Congenital or acquired valvular disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension;
b. Pericardial constriction;
c. Restrictive or congestive cardiomyopathy;
d. Left ventricular ejection fraction < 40% per echocardiogram (ECHO) within 90 days of Day 1;
e. Symptomatic coronary artery disease within the last 3 years;
10. Acutely decompensated heart failure within 30 days prior to Day 1, per investigator assessment;
11. Has more than two of the following clinical risk factors for left ventricular diastolic dysfunction:
a. Age > 65 years;
b. BMI ≥ 30 kg/m2;
c. History of systemic hypertension;
d. History of type 2 diabetes;
e. History of atrial fibrillation;
12. History of atrial septostomy within 180 days prior to Day 1;
13. Uncontrolled obstructive sleep apnea;
14. Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Xxxx Class A-C);
15. Serum aminotransferase (ALT or AST) levels > 1.5X the upper limit of normal (ULN) at Screening;
16. Hemoglobin (Hgb) concentration < 10.5 g/dL at Sc...
