The investigational drug bardoxolone methyl is a capsule taken by mouth that has been tested in clinical studies with different diseases, including CKD, cancer, and pulmonary hypertension. The most common side effects have included muscle cramps and nausea.
A previous large study in over 2000 diabetic patients with severe, stage 3 and 4 chronic kidney disease was stopped early because bardoxolone methyl increased the risk for fluid retention in a subset of patients who had previously been hospitalized for heart failure and who had fluid retention prior to the start of the study.
The increased risk for fluid retention was observed in the first month after starting treatment. The identified risk factors are a history of serious cardiovascular disease or heart failure, and are now used to exclude patients who are more likely to retain fluid from participating in studies with bardoxolone methyl.
FALCON will exclude patients with stage 4 chronic kidney disease and these risk factors. Additionally, patients will be monitored closely during the first two months of the trial to ensure they do not develop fluid retention.
Bardoxolone Methyl Research for Potential Treatment of ADPKD
Your estimated glomerular filtration rate (eGFR) is an estimate of how well your kidneys are working. In patients with ADPKD, genetic mutations in PKD1 and PKD2 genes lead to the formation of fluid-filled cysts in the kidneys and other organs. The cysts continue to grow and can cause the kidneys to expand up to five to seven times their normal volume, leading to pain and progressive loss of kidney function and decrease in eGFR. As in other forms of CKD, decreased mitochondrial function and chronic inflammation are key drivers of disease progression in ADPKD. Decreasing eGFR ultimately results in the need for dialysis or kidney transplant.
In previous studies in patients with diabetes and chronic kidney disease, bardoxolone methyl produced an increase in estimated GFR (eGFR) that was sustained for 1 year in some patients. It is not known whether an increase in eGFR, if achieved, will provide long-term benefit in patients with ADPKD. Consequently, FALCON is designed to test the effects of bardoxolone methyl on eGFR in patients with ADPKD through 2 years of treatment.