Effect of Oral JTT-751 (Ferric Citrate) on Hyperphosphatemia in Hemodialysis Patients: Results of a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background/Aims: 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.

Effects and safety of iron-based phosphate binders in dialysis patients: a systematic review and meta-analysis

“…The remaining 18 full-text articles were reviewed for more detailed assessment, and 10 studies were excluded because of duplicate reports. Finally, 8 studies [15][16][17][18][19][20][21][22] with 2018 participants met our inclusion criteria and were included in our meta-analysis. The selection process for studies included in the systematic review is shown in Figure 1.…”

“…The mean age of the participants ranged from 52.5 to 62.8 years. Seven studies [15][16][17][18][19]21,22 were parallel randomized controlled trials, while one study 20 was cross-over randomized controlled trial. Three studies 17,18,22 compared iron-based phosphate binders with placebo, four studies 16,17,19,21 made comparison between iron-based phosphate binders and sevelamer, and one study 20 compared ferric citrate with calcium carbonate.…”

“…Three studies 17,18,22 compared iron-based phosphate binders with placebo, four studies 16,17,19,21 made comparison between iron-based phosphate binders and sevelamer, and one study 20 compared ferric citrate with calcium carbonate. Of the eight included trials, five 15,17,[20][21][22] were conducted in Asia. Two studies 16,17 recruited both hemodialysis and peritoneal dialysis patients and six studies 15,[18][19][20][21][22] included only hemodialysis patients.…”

“…Of the eight included trials, five 15,17,[20][21][22] were conducted in Asia. Two studies 16,17 recruited both hemodialysis and peritoneal dialysis patients and six studies 15,[18][19][20][21][22] included only hemodialysis patients. Six studies 15,16,[19][20][21][22] made dietary recommendations or monitored the dietary phosphate intake for the participants.…”

“…Random sequence generations were adequate in three studies. 18,19,22 Allocation concealments were adequately described with low risk of bias in two studies 18,22 and unclear in other six studies. Participants and investigators were blinded in three studies 17,18,22 and outcome assessors were blinded in four studies.…”