A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients

Abstract

Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0 g per day and 348 received sevelamer 4.8–14.4 g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were −0.71 mmol/l (PA21) and −0.79 mmol/l (sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250 mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to sevelamer carbonate, a lower pill burden, and better adherence.

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.…”

“…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. Of the eight included trials, five 15,17,[20][21][22] were conducted in Asia.…”

“…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.…”

“…Four studies 15,16,19,21 compared iron-based phosphate binders with sevelamer, one study 21 compared JTT-751 with sevelamer, two studies 16,19 made comparison between PA21 and sevelamer, and the other study 15 compared SBR759 to sevelamer. Treatment duration ranged from 6 to 24 weeks and sample size varied from 154 to 1059.…”

“…Three studies 16,19,21 reported the effect of iron-based phosphate binders on serum phosphorus (expressed as mean ± standard deviation) and were pooled in our metaanalysis. There was no significant difference in serum phosphorus between iron-based phosphate binders and sevelamer (MD ¼ 0.04 mg/dL, 95% CI À0.29 to 0.36, p ¼ 0.83), with significant heterogeneity among studies (Chi 2 ¼ 7.82, I 2 ¼ 74%) (Figure 6a).…”