Dose-response efficacy and safety of PA21 in Japanese hemodialysis patients with hyperphosphatemia: a randomized, placebo-controlled, double-blind, Phase II study

Abstract

Background: Hyperphosphatemia is common in chronic kidney disease (CKD) and associated with mortality and morbidity. We aimed to evaluate the dose-dependent efficacy and safety of PA21 (sucroferric oxyhydroxide), an iron-based phosphate binder, in Japanese hemodialysis patients with hyperphosphatemia.

Methods: In this double-blind, multicenter, Phase II study, 183 patients were randomized to placebo or PA21 at doses of 250, 500, 750, or 1000 mg (based on iron content) three times/day for 6 weeks. The primary efficacy endpoint was the mean change in serum phosphorus levels from baseline to end of treatment in each group. Adverse reactions were evaluated.

Results: The change in serum phosphorus level was significantly greater in each PA21 group than in the placebo group (analysis of covariance: P < 0.001 for all groups). A dose-dependent change in serum phosphorus levels was observed in the PA21 groups. A notable decrease in mean serum phosphorus levels to the target level of ≤6 mg/dL was shown starting at Week 1 in all PA21 groups. The cumulative achievement rates for target serum phosphorus level at the end of treatment were generally >80 % in all PA21 groups. The major adverse reaction reported was diarrhea; however, most cases were mild.

Conclusions: PA21 was an effective and safe treatment that decreased serum phosphorus levels starting at 1 week of treatment when administered as one 250-mg tablet three times/day. PA21 demonstrated a dose-dependent phosphorus lowering effect up to 3000 mg/day. PA21 may be a new treatment alternative with relatively low pill burden for Japanese hemodialysis patients with hyperphosphatemia.

Keywords: Hemodialysis; Hyperphosphatemia; Japanese; PA21 compound; Phosphate binder; Sucroferric oxyhydroxide.

Fig. 1

Disposition of patients. Some subjects had more than one reason for discontinuation. Abbreviations Ca calcium, P phosphorus

Fig. 2

Change from baseline to end of treatment in serum phosphorus levels (full analysis set). The changes in serum phosphorus levels from baseline to end of treatment are adjusted for serum phosphorus levels at baseline. ANCOVA: * P < 0.001 for all PA21 groups vs placebo

Fig. 3

Time course of mean serum phosphorus levels (full analysis set). The mean serum phosphorus levels were significantly higher in all the PA21 groups in all the time-points after administering the PA21 dose (all P < 0.001, one-sample t test)

Fig. 4

Cumulative achievement rates of target serum phosphorus levels (≤6.0 mg/dL) (full analysis set). The numbers of patients analyzed in the 750-, 1500-, 2250-, 3000-mg, and placebo group were 36, 32, 32, 29, and 31, respectively. The cumulative achievement rates were significantly higher in all the PA21 groups than in the placebo group (all * P < 0.001, Fisher’s exact test)