Long-term safety and efficacy of a novel iron-containing phosphate binder, JTT-751, in patients receiving hemodialysis.
OBJECTIVE
JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient. This study investigated long-term safety and efficacy of JTT-751 for hyperphosphatemia in patients receiving hemodialysis.


METHODS
This was 52-week, phase 3, multicenter, open-label, dose titration, long-term study. All patients were receiving thrice-weekly hemodialysis for ≥3 months before the initiation of the study. JTT-751 was given at titrated doses between 1.5 and 6.0 g/day.


METHODS
Safety endpoints were adverse events and adverse drug reactions. Efficacy outcomes were the change in serum phosphate, corrected serum calcium, and intact parathyroid hormone. Changes in ferritin, transferrin saturation, and doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron formulations were additional outcomes.


RESULTS
One hundred and eighty patients were included in the trial. Dose-titrated JTT-751 decreased mean serum phosphate after administration and satisfactorily maintained serum phosphate concentrations throughout the entire duration of the 52-week trial. Mean serum phosphate concentrations were kept lower than 5.5 mg/dL from weeks 5 to 52. The most common adverse events were gastrointestinal disorders, which were mild to moderate in intensity. Serum ferritin concentrations rose to a peak around week 28 and stabilized thereafter. The mean intravenous iron dose decreased from 57.3 mg/4 weeks (weeks 0-12) to 3.6 mg/4 weeks (weeks 28-52); weekly ESA dose declined by 25% over the same time frame, while mean hemoglobin concentrations remained stable.


CONCLUSIONS
JTT-751 1.5-6.0 g/day controls serum phosphorus concentrations and reduces the need for ESAs and intravenous iron in patients receiving hemodialysis.
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: keitaro@jikei.ac.jp.
Keitaro
K
Yokoyama
Department of Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Takashi
T
Akiba
Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.
Masafumi
M
Fukagawa
Department of Nephrology, Hypertension, Diabetology, Endocrinology, and Metabolism, Fukushima Medical University School of Medicine, Fukushima, Japan.
Masaaki
M
Nakayama
Department of Hematology, Nephrology, and Rheumatology, Akita University, Akita, Japan.
Kenichi
K
Sawada
Kitasato University East Hospital Clinical Trial Center, Sagamihara, Japan.
Yuji
Y
Kumagai
Division of Nephrology, Stanford University School of Medicine, Palo Alto, California.
Glenn M
GM
Chertow
Japanese Red Cross, Fukuoka Hospital, Fukuoka, Japan.
Hideki
H
Hirakata
D000368:Aged; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D005293:Ferritins / Q000097:blood; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000503:physiopathology; D006397:Hematinics / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D054559:Hyperphosphatemia; D007501:Iron / Q000008:administration & dosage / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis
D005290:Ferric Compounds; D006397:Hematinics; D010281:Parathyroid Hormone; D010710:Phosphates; D010758:Phosphorus; C025314:ferric citrate; D005293:Ferritins; D007501:Iron; D002118:Calcium