title: Randomized clinical trial of the iron-based phosphate binder PA21 in hemodialysis patients.
abstract: OBJECTIVE
  A dose-finding study was undertaken to investigate the efficacy of PA21, a novel polynuclear iron(III)-oxyhydroxide phosphate binder.
  
  
  METHODS
  In a randomized, active-controlled, multicenter, open-label study at 50 clinical sites in Europe and the United States, hemodialysis patients were randomized to PA21 at dosages of 1.25, 5.0, 7.5, 10.0, or 12.5 g/d or sevelamer-HCl 4.8 g/d for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus concentration from baseline.
  
  
  RESULTS
  There were 154 participants who were randomized and received the study drug. All groups except PA21 1.25 g/d showed a significant decrease in serum phosphorus. Mean decreases in serum phosphorus in PA21 10 g/d and 12.5 g/d were -2.00±1.71 mg/dl and -1.69±1.81 mg/dl, respectively. A similar decrease to sevelamer-HCl (-1.06±1.35 mg/dl) was seen with PA21 5.0 g/d (-1.08±2.12 mg/dl) and 7.5 g/d (-1.25±1.21 mg/d). Overall, 60.9% of participants randomized to PA21 and 57.7% randomized to sevelamer-HCl reported ≥1 adverse event. The most frequent adverse events were hypophosphatemia (18.0%) and discolored feces (11.7%) for the pooled PA21 dose groups, and diarrhea, hypophosphatemia, and hypotension (each 11.5%) for sevelamer-HCl. Discontinuation due to adverse events occurred at a similar rate in PA21-treated (21.1%) and sevelamer-HCl-treated (23.1%) participants.
  
  
  CONCLUSIONS
  PA21 5-12.5 g/d significantly reduces serum phosphorus in hemodialysis patients. The 5 g/d and 7.5 g/d dosages showed similar efficacy to 4.8 g/d of sevelamer-HCl. The adverse events rate was similar for PA21 and sevelamer-HCl.
authors.affiliation: Division of Nephrology, University Hospital, Zürich, Switzerland. rudolf.wuethrich@usz.ch
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Michel
authors.initials: M
authors.lastname: Chonchol
authors.forename: Adrian
authors.initials: A
authors.lastname: Covic
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gaillard
authors.forename: Edward
authors.initials: E
authors.lastname: Chong
authors.forename: James A
authors.initials: JA
authors.lastname: Tumlin
mesh_terms: D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D006801:Humans; D054559:Hyperphosphatemia / Q000209:etiology* / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D005290:Ferric Compounds; C552479:PA21 compound