title: Dose-response efficacy and safety of PA21 in Japanese hemodialysis patients with hyperphosphatemia: a randomized, placebo-controlled, double-blind, Phase II study.
abstract: BACKGROUND
  Hyperphosphatemia is common in chronic kidney disease (CKD) and associated with mortality and morbidity. We aimed to evaluate the dose-dependent efficacy and safety of PA21 (sucroferric oxyhydroxide), an iron-based phosphate binder, in Japanese hemodialysis patients with hyperphosphatemia.
  
  
  METHODS
  In this double-blind, multicenter, Phase II study, 183 patients were randomized to placebo or PA21 at doses of 250, 500, 750, or 1000 mg (based on iron content) three times/day for 6 weeks. The primary efficacy endpoint was the mean change in serum phosphorus levels from baseline to end of treatment in each group. Adverse reactions were evaluated.
  
  
  RESULTS
  The change in serum phosphorus level was significantly greater in each PA21 group than in the placebo group (analysis of covariance: P < 0.001 for all groups). A dose-dependent change in serum phosphorus levels was observed in the PA21 groups. A notable decrease in mean serum phosphorus levels to the target level of ≤6 mg/dL was shown starting at Week 1 in all PA21 groups. The cumulative achievement rates for target serum phosphorus level at the end of treatment were generally >80 % in all PA21 groups. The major adverse reaction reported was diarrhea; however, most cases were mild.
  
  
  CONCLUSIONS
  PA21 was an effective and safe treatment that decreased serum phosphorus levels starting at 1 week of treatment when administered as one 250-mg tablet three times/day. PA21 demonstrated a dose-dependent phosphorus lowering effect up to 3000 mg/day. PA21 may be a new treatment alternative with relatively low pill burden for Japanese hemodialysis patients with hyperphosphatemia.
authors.affiliation: Division of Nephrology, Department of Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan. koiwa-f@med.showa-u.ac.jp.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Koiwa
authors.affiliation: Biostatistics, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Terao
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002614:Chelating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D007564:Japan; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002614:Chelating Agents; D005290:Ferric Compounds; C552479:PA21 compound; D010758:Phosphorus
keywords: Hemodialysis; Hyperphosphatemia; Japanese; PA21 compound; Phosphate binder; Sucroferric oxyhydroxide