title: Efficacy and safety of SBR759, a novel calcium-free, iron (III)-based phosphate binder, versus placebo in chronic kidney disease stage V Japanese patients on maintenance renal replacement therapy.
abstract: BACKGROUND
  SBR759, an iron (III)-based oral phosphate binder, was developed for the treatment of hyperphosphataemia in chronic kidney disease stage V patients receiving maintenance renal replacement therapy (RRT). Serum phosphate-lowering efficacy and dose response of SBR759 (3-, 6-, 9- and 12-g/day doses) were compared with placebo.
  
  
  METHODS
  Japanese patients with hyperphosphataemia (P ≥ 5.5 mg/dL [≥ 1.78 mmol/L]) receiving maintenance RRT (N = 63) were randomised to receive either SBR759 (3-, 6-, 9-, 12-g/day dose) or placebo (12-g/day dose) for 4 weeks. The primary endpoint was change from baseline in 72-h post-dialysis serum phosphate levels at week 4 for different doses of SBR759 versus placebo. Secondary endpoints were change from baseline in serum phosphate levels and dose-dependent efficacy of SBR759 during the 4-week treatment period.
  
  
  RESULTS
  SBR759 showed significant reduction in serum phosphate levels compared with placebo at week 4, demonstrating a significant linear dose response (P < 0.001). Incidence of adverse events was comparable between the SBR759 treatment groups (7/13 and 5/12 in the 3- and 12-g/day groups, respectively, and 8/13 in the 6- and 9-g/day groups) and was 6/12 in the placebo group. Discoloured faeces and diarrhoea were the most frequently reported adverse events. Two serious adverse events were reported--one in the SBR759 3-g/day group (1/13, skin ulcer) and one in the SBR759 12-g/day group (1/12, arthralgia).
  
  
  CONCLUSIONS
  SBR759 showed significant phosphate-lowering efficacy and dose-dependent response compared with placebo in patients with chronic kidney disease receiving RRT.
authors.affiliation: Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan, fukagawa@tokai-u.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.forename: Hirotake
authors.initials: H
authors.lastname: Kasuga
authors.forename: Devanand
authors.initials: D
authors.lastname: Joseph
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sawata
authors.forename: Guido
authors.initials: G
authors.lastname: Junge
authors.forename: Alan
authors.initials: A
authors.lastname: Moore
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiba
mesh_terms: D015415:Biomarkers / Q000097:blood; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005290:Ferric Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology; D007564:Japan; D016014:Linear Models; D010710:Phosphates / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000628:therapy*; D012720:Severity of Illness Index; D013213:Starch / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; D004338:Drug Combinations; D005290:Ferric Compounds; D010710:Phosphates; C570356:SBR 759; D013213:Starch