Background/Aims: JTT-751 (ferric citrate hydrate) is a novel iron-based phosphate approved in Japan for the treatment of hyperphosphatemia in dialysis and nondialysis patients with chronic kidney disease. Methods: In this phase 3, multicenter, open-label, dose-adjusted study, we investigated the efficacy and safety of JTT-751 in peritoneal dialysis patients. A total of 56 patients with serum phosphate ≥5.6 and <10.0 mg/dl were enrolled in the study. The dose of JTT-751 was adjusted to between 1.5 and 6.0 g/day, according to the target range of serum phosphate (3.5-5.5 mg/dl), for 12 weeks. The primary endpoint was change in serum phosphate from baseline to end of treatment. Secondary endpoints included the percentage of patients achieving target serum phosphate levels and changes in intact parathyroid hormone. Results: Serum phosphate was significantly reduced by 2.26 mg/dl (p < 0.001). The percentage of patients achieving target serum phosphate levels was 76.8%. Intact parathyroid hormone decreased significantly (p < 0.001). The most common adverse drug reactions were diarrhea and constipation. Most of the events were considered to be mild. Treatment with JTT-751 resulted in significant increases in serum ferritin and transferrin saturation (p < 0.001). Conclusion: In peritoneal dialysis patients with hyperphosphatemia, 12-week treatment with JTT-751 resulted in significant reductions in serum phosphate while simultaneously increasing serum iron parameters. JTT-751 was well tolerated.

Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G; Kidney Disease Improving Global Outcomes (KDIGO): Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69:1945-1953.
Block GA, Hulbert-Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium × phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998;31:607-617.
Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-2218.
Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC: Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 1996;27:394-401.
Sarnak MJ: Cardiovascular complications in chronic kidney disease. Am J Kidney Dis 2003;41(suppl 5):11-17.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009;113:S1−S130.
Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama J, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Shigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T; CKD-MBD Guideline Working Group, Japanese Society for Dialysis Therapy: Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial 2013;17:247−288.
National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42(suppl 3):S1-S201.
Nagina A: Phosphate binders in CKD - past, present, and future. J Indian Acad Clin Med 2009;10:43-45.
Tonelli M, Pannu N, Manns B: Oral phosphate binders in patients with kidney failure. N Engl J Med 2010;362:1312-1324.
Feng L, Xiao H, He X, Li Z, Liu N, Zhao Y, Huang Y, Zhang Z, Chai Z: Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett 2006;165:112-120.
Slatopolsky E, Liapis H, Finch J: Progressive accumulation of lanthanum in the liver of normal and uremic rats. Kidney Int 2005;68:2809-2813.
Sinsakul M, Sika M, Koury M, Shapiro W, Greene T, Dwyer J, Smith M, Korbet S, Lewis J; Collaborative Study Group: The safety and tolerability of ferric citrate as a phosphate binder in dialysis patients. Nephron Clin Pract 2012;121:c25-c29.
Dwyer JP, Sika M, Schulman G, Chang IJ, Anger M, Smith M, Kaplan M, Zeig S, Koury MJ, Blumenthal SS, Lewis JB; Collaborative Study Group: Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients: a short-term randomized trial. Am J Kidney Dis 2013;61:759-766.
Iida A, Kemmochi Y, Kakimoto K, Tanimoto M, Mimura T, Shinozaki Y, Uemura A, Matsuo A, Matsushita M, Miyamoto K: Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification. Am J Nephrol 2013;37:346-358.
Yokoyama K, Hirakata H, Akiba T, Sawada K, Kumagai Y: Effect of oral JTT-751 (ferric citrate) on hyperphosphatemia in hemodialysis patients: results of a randomized, double-blind, placebo-controlled trial. Am J Nephrol 2012;36:478-487.
Yokoyama K, Akiba T, Fukagawa M, Nakayama M, Sawada K, Kumigai Y, Chertow GM, Hirakata H: A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis. Nephrol Dial Transplant 2014;29:1053-1060.
Cozzolino M, Stucchi A, Rizzo MA, Brenna I, Elli F, Ciceri P, Bover J, Cusi D, Gallieni M: Phosphate control in peritoneal dialysis. Contrib Nephrol. Basel, Karger, 2012, vol 178, pp 116-123.
Evenepoel P, Selgas R, Caputo F, Foggensteiner L, Heaf JG, Ortiz A, Kelly A, Chasan-Taber S, Duggal A, Fan S: Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis. Nephrol Dial Transplant 2009;24:278-285.
Hutchison AJ, Gill M, Copley B, Poole L, Wilson RJ: Lanthanum carbonate versus placebo for management of hyperphosphatemia in patients undergoing peritoneal dialysis: a subgroup analysis of a phase 2 randomized controlled study of dialysis patients. BMC Nephrol 2013;14:40.
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