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

Floege J, Covic AC, Ketteler M, Rastogi A, Chong EM, Gaillard S, Lisk LJ, Sprague SM, PA21 Study Gro - Kidney Int. (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, RWTH University Hospital Aachen, Aachen, Germany.

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.

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Mean (±s.d.) serum phosphorus concentrations in stage 2 (primary efficacy set (PES); N=93). LOCF, last observation carried forward.
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fig5: Mean (±s.d.) serum phosphorus concentrations in stage 2 (primary efficacy set (PES); N=93). LOCF, last observation carried forward.

Mentions: At week 24, mean serum phosphorus concentrations in the primary efficacy set were similar in both treatment groups: 1.5 mmol/l in the maintenance dose (MD) group (n=50) and 1.6 mmol/l in the LD group (n=49; Figure 5). In the MD group, mean serum phosphorus concentrations did not change significantly from weeks 24 to 27. However, in the LD group mean values increased by 0.6 mmol/l, which was significantly higher than that in the MD group (P<0.001), thereby demonstrating superiority of the MD group. There were no significant interactions of demographic and disease covariates with treatment effects. Similar results were obtained for the primary efficacy per-protocol set.


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

Floege J, Covic AC, Ketteler M, Rastogi A, Chong EM, Gaillard S, Lisk LJ, Sprague SM, PA21 Study Gro - Kidney Int. (2014)

Mean (±s.d.) serum phosphorus concentrations in stage 2 (primary efficacy set (PES); N=93). LOCF, last observation carried forward.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150998&req=5

fig5: Mean (±s.d.) serum phosphorus concentrations in stage 2 (primary efficacy set (PES); N=93). LOCF, last observation carried forward.
Mentions: At week 24, mean serum phosphorus concentrations in the primary efficacy set were similar in both treatment groups: 1.5 mmol/l in the maintenance dose (MD) group (n=50) and 1.6 mmol/l in the LD group (n=49; Figure 5). In the MD group, mean serum phosphorus concentrations did not change significantly from weeks 24 to 27. However, in the LD group mean values increased by 0.6 mmol/l, which was significantly higher than that in the MD group (P<0.001), thereby demonstrating superiority of the MD group. There were no significant interactions of demographic and disease covariates with treatment effects. Similar results were obtained for the primary efficacy per-protocol set.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, RWTH University Hospital Aachen, Aachen, Germany.

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.

Show MeSH
Related in: MedlinePlus