title: Effect of oral JTT-751 (ferric citrate) on hyperphosphatemia in hemodialysis patients: results of a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  JTT-751 (ferric citrate hydrate) is a novel oral, iron-based phosphate binder being developed for the treatment of hyperphosphatemia among chronic kidney disease patients who are on dialysis. This study investigated the dose-response and safety of JTT-751 among Japanese hemodialysis patients.
  
  
  METHODS
  This was a multicenter, randomized, placebo-controlled, double-blind, parallel-group, comparative study. A total of 192 subjects with serum phosphorus (P) levels between 6.1 and 10.0 mg/dl were randomized to JTT-751 (1.5, 3 or 6 g/day) or to placebo treatment for 28 days. Changes in serum P level from baseline were examined.
  
  
  RESULTS
  In the full analysis set, the mean change in serum P level at week 4 was 0.04, -1.28, -2.16 and -4.10 mg/dl in the placebo, 1.5-grams, 3-grams and 6-grams/day groups, respectively, demonstrating a dose-response relationship up to 6 g/day. Overall, a reduction in serum P levels to ≤5.5 mg/dl was achieved in 2.5, 16.7, 50.0 and 92.6% of subjects, in the placebo, 1.5-grams, 3-grams and 6-grams/day groups, respectively. The most common adverse events (AEs) were gastrointestinal disorders. Most AEs were mild. In 25 patients, treatment was discontinued due to increased transferrin saturation ≥50%; however, this was not considered to be a safety issue.
  
  
  CONCLUSIONS
  When hemodialysis subjects received JTT-751 at doses between 1.5 and 6 g/day for 28 days, serum P levels were significantly reduced in a dose-dependent manner (p < 0.001). JTT-751 was found to be efficacious and safe, with the majority of subjects in the 6-grams/day group achieving a serum P level of ≤5.5 mg/dl.
authors.affiliation: Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. keitaro@jikei.ac.jp
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirakata
authors.forename: Takashi
authors.initials: T
authors.lastname: Akiba
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sawada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kumagai
mesh_terms: D004311:Double-Blind Method; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use*; D006801:Humans; D054559:Hyperphosphatemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D005290:Ferric Compounds; C025314:ferric citrate