title: Bardoxolone methyl and kidney function in CKD with type 2 diabetes.
abstract: BACKGROUND
  Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined.
  
  
  METHODS
  In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m(2) of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the estimated GFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks.
  
  
  RESULTS
  Patients receiving bardoxolone methyl had significant increases in the mean (±SD) estimated GFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m(2) of 8.2±1.5 ml in the 25-mg group, 11.4±1.5 ml in the 75-mg group, and 10.4±1.5 ml in the 150-mg group; P<0.001). The increases were maintained through week 52, with significant differences per minute per 1.73 m(2) of 5.8±1.8 ml, 10.5±1.8 ml, and 9.3±1.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl.
  
  
  CONCLUSIONS
  Bardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone methyl may have promise for the treatment of CKD. (Funded by Reata Pharmaceuticals; BEAM ClinicalTrials.gov number, NCT00811889.).
authors.affiliation: Renal Associates, San Antonio, TX 78215, USA. ppergola@raparesearch.com
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Pergola
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: Robert D
authors.initials: RD
authors.lastname: Toto
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Meyer
authors.forename: J Warren
authors.initials: JW
authors.lastname: Huff
authors.forename: Eric B
authors.initials: EB
authors.lastname: Grossman
authors.forename: Melissa
authors.initials: M
authors.lastname: Krauth
authors.forename: Stacey
authors.initials: S
authors.lastname: Ruiz
authors.forename: Paul
authors.initials: P
authors.lastname: Audhya
authors.forename: Heidi
authors.initials: H
authors.lastname: Christ-Schmidt
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013035:Spasm / Q000139:chemically induced
chemical_list: D000975:Antioxidants; D009828:Oleanolic Acid; C445068:bardoxolone methyl