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Clinical Trial
. 2017 Apr;22(4):293-300.
doi: 10.1111/nep.12891.

Efficacy and safety of sucroferric oxyhydroxide compared with sevelamer hydrochloride in Japanese haemodialysis patients with hyperphosphataemia: A randomized, open-label, multicentre, 12-week phase III study

Fumihiko Koiwa  1 , Keitaro Yokoyama  2 , Masafumi Fukagawa  3 , Akira Terao  4 , Tadao Akizawa  5
Affiliations
Clinical Trial

Efficacy and safety of sucroferric oxyhydroxide compared with sevelamer hydrochloride in Japanese haemodialysis patients with hyperphosphataemia: A randomized, open-label, multicentre, 12-week phase III study

Fumihiko Koiwa et al. Nephrology (Carlton). 2017 Apr.

Abstract

Aim: We aimed to investigate the non-inferiority of PA21 (sucroferric oxyhydroxide) to sevelamer hydrochloride (sevelamer) in terms of efficacy and safety in Japanese haemodialysis patients with hyperphosphataemia.

Methods: In this Phase III, open-label, multicentre study, 213 haemodialysis patients with hyperphosphataemia were randomized to PA21 or sevelamer treatment for 12 weeks. The primary outcome was adjusted serum phosphorus concentration at the end of treatment; the non-inferiority of PA21 was confirmed if the upper limit of the two-sided 95% confidence interval (CI) is ≤0.32 mmol/L. Secondary outcomes were corrected serum calcium and intact-parathyroid hormone concentrations. Adverse events (AEs) and adverse drug reactions (ADRs) were evaluated.

Results: The adjusted mean serum phosphorus concentration at the end of treatment confirmed the non-inferiority of PA21 for lowering serum phosphorus compared with sevelamer (1.62 vs 1.72 mmol/L; difference, -0.11 mmol/L; 95% CI, -0.20 to -0.02 mmol/L). The mean daily tablet intake was 5.6 ± 2.6 and 18.7 ± 7.1 tablets in the PA21 and sevelamer groups, respectively. The incidences of AEs and ADRs were not significantly different between the two groups.

Conclusion: The non-inferiority of PA21 to sevelamer was confirmed for the treatment of Japanese haemodialysis patients with hyperphosphataemia. PA21 was effective, safe, and well tolerated, while having a considerably lower pill burden than sevelamer.

Keywords: PA21 compound; haemodialysis; hyperphosphataemia; sevelamer; sucroferric oxyhydroxide.

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Figures

Figure 1
Figure 1
Patient disposition. aSome subjects had more than one reason for discontinuation. FAS, full analysis set; PPS, per protocol set; SS, safety set.
Figure 2
Figure 2
Serum phosphorus concentrations (mean + SD) (per protocol set). The adjusted mean serum phosphorus concentration at the end of treatment confirmed the non‐inferiority of PA21 (sucroferric oxyhydroxide) to sevelamer (1.62 vs 1.72 mmol/L; difference, −0.11 mmol/L; 95% CI, −0.20 to −0.02 mmol/L; ANCOVA, P = 0.020). A notable decrease in serum phosphorus concentrations was shown at Week 1 in both groups and was maintained until Week 12. The horizontal lines indicate the target range of serum phosphorus concentration in the JSDT guideline. ANCOVA, analysis of covariance; CI, confidence interval; EP, endpoint; SD, standard deviation.
Figure 3
Figure 3
Mean daily number of tablets for daily dose of PA21 (sucroferric oxyhydroxide) and sevelamer (per protocol set). The mean number of tablets for daily dose of PA21 was notably lower than that of sevelamer.
Figure 4
Figure 4
Achievement rates of target serum phosphorus concentration (per protocol set). The achievement rates of target serum phosphorus concentration (1.13–1.94 mmol/L) at the end of treatment were 82.0% and 67.4% in the PA21 (sucroferric oxyhydroxide) and sevelamer groups, respectively. The rates were >80% in the PA21 group after Week 6. Meanwhile, the rates were significantly higher in the PA21 group than in the sevelamer group after Week 8. EP, endpoint. *P < 0.05.
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References

    1. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J. Am. Soc. Nephrol. 2004; 15: 2208–2218. - PubMed
    1. Kalantar‐Zadeh K, Kuwae N, Regidor DL et al. Survival predictability of time‐varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006; 70: 771–780. - PubMed
    1. Fukagawa M, Yokoyama K, Koiwa F et al. Clinical practice guideline for the management of chronic kidney disease‐mineral and bone disorder. Ther. Apher. Dial. 2013; 17: 247–288. - PubMed
    1. National Kidney Foundation . K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am. J. Kidney Dis. 2003; 42: S1–S201. - PubMed
    1. Bleyer AJ, Burke SK, Dillon M et al. A comparison of the calcium‐free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am. J. Kidney Dis. 1999; 33: 694–701. - PubMed

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