Efficacy and Safety of Sucroferric Oxyhydroxide Compared with Sevelamer Carbonate in Chinese Dialysis Patients with Hyperphosphataemia: A Randomised, Open-Label, Multicentre, 12-Week Phase III Study

Abstract

Introduction: This study aimed to investigate the efficacy and safety of sucroferric oxyhydroxide (SFOH) versus sevelamer carbonate in controlling serum phosphorus (sP) in adult Chinese dialysis patients with hyperphosphataemia (sP >1.78 mmol/L).

Methods: Open-label, randomised (1:1), active-controlled, parallel group, multicentre, phase III study of SFOH and sevelamer at starting doses corresponding to 1,500 mg iron/day and 2.4 g/day, respectively, with 8-week dose titration and 4-week maintenance (NCT03644264). Primary endpoint was non-inferiority analysis of change in sP from baseline to week 12. Secondary endpoints included sP over time and safety.

Results: 415 patients were screened; 286 were enrolled and randomised (142 and 144 to SFOH and sevelamer, respectively). Mean (SD) baseline sP: 2.38 (0.57) and 2.38 (0.52) mmol/L, respectively. Mean (SD) change in sP from baseline to week 12: - 0.71 (0.60) versus -0.63 (0.52) mmol/L, respectively; difference (sevelamer minus SFOH) in least squares means (95% CI): 0.08 mmol/L (-0.02, 0.18) with the lower limit of 95% CI above the non-inferiority margin of -0.34 mmol/L. The SFOH group achieved target sP (1.13-1.78 mmol/L) earlier than the sevelamer group (56.5% vs. 32.8% at week 4) and with a lower pill burden (mean 3.7 vs. 9.1 tablets/day over 4 weeks of maintenance, respectively). Safety and tolerability of SFOH was consistent with previous studies, and no new safety signals were observed.

Conclusion: SFOH effectively reduced sP from baseline and was non-inferior to sevelamer after 12 weeks of treatment but had a lower pill burden in Chinese dialysis patients with hyperphosphataemia; SFOH benefit-risk profile is favourable in Chinese patients.

Keywords: Chronic kidney disease; Hyperphosphataemia; Phosphate binder; Sucroferric oxyhydroxide.

Fig. 1.

Study design. SFOH, sucroferric oxyhydroxide.

Fig. 2.

Patient disposition. SFOH, sucroferric oxyhydroxide.

Fig. 3.

Primary outcome: sP change from baseline to week 12: LOCF endpoint (PPS). ^†Values from both central and local laboratories were considered; however, local laboratory assessment was considered only if the central laboratory assessment was missing. Change in sP levels from baseline to week 12 (stage 2) was computed as if the sP level at week 12 (stage 2) analysis visit was missing or was 2 days after the last day of study treatment administration or later, then LOCF approach was applied, and the LOCF was the last on-treatment laboratory value available excluding all data before the week 4 (stage 1) analysis visit but including values on the day after the last day of study treatment. The box is defined by two lines, Q1 (lower) and Q3 (upper), and the distance between both lines of the box is the interquartile range (IQR). Inside the box, the line represents the median (Q2), while the dot represents the mean. The whisker boundaries represent the minimum and maximum. LOCF, last observation carried forward; PPS, per-protocol set; SFOH, sucroferric oxyhydroxide.

Fig. 4.

Secondary efficacy outcomes (PPS). a Absolute sP values over time (central and local laboratories). sP levels up to week 12 (stage 2) were computed as done for the primary endpoint, i.e., if sP level at week 12 (stage 2) analysis visit was missing or was 2 days after the last day of study treatment administration or later, then the LOCF approach was applied, and the LOCF was the last on-treatment laboratory value available excluding all data before the week 4 (stage 1) analysis visit but including values on the day after the last day of study treatment. Values from both central and local laboratories were considered; however, local laboratory assessment was considered only if the central laboratory assessment was missing. b Percentage of patients with sP within the target range. The target range was defined as sP 1.13–1.78 mmol/L (3.5–5.5 mg/dL). On-treatment values as well as values on the day after the last dose from both central and local laboratory assessments were considered; however, central laboratory values were used in preference to local laboratory values. LOCF, last observation carried forward; PPS, per-protocol set; SEM, standard error of the mean; SFOH, sucroferric oxyhydroxide; sP, serum phosphorus.