Lanthanum Carbonate Treatment of Patients with Hyperphosphatemia Undergoing CAPD

Editor: Lanthanum carbonate is a new non-aluminumand non-calcium-containing phosphate binder that has recently become available for the management of hyperphosphatemia in patients with end-stage renal disease (FDA approval in 2004). Oral administration effectively decreases phosphate absorption from the gastrointestinal tract by the formation, and then excretion, of highly insoluble complexes with dietary phosphate (1). Its efficacy has been reported in many clinical trials in hemodialysis patients (2,3) but there have not been any reports published of data specifically obtained from patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Therefore, an open, non-comparative dose-escalation study of lanthanum carbonate to assess its safety and efficacy in reducing serum phosphate levels in subjects with hyperphosphatemia undergoing CAPD was undertaken. Male and female patients aged 20 years or older, with hyperphosphatemia, and undergoing CAPD for at least 3 months were enrolled in this study. Serum phosphate level had to be ≥5.0 mg/dL and <11.0 mg/dL at 2 weeks after the initiation of the washout period (serum phosphate level was above the recommended KDOQI level in all patients). Patients were excluded from the study if they met any of the following exclusion criteria: (1) a serum phosphate level ≥10.0 mg/dL at the start of the washout period (week –2), or ≥11.0 mg/dL at the end of the washout (week 0); (2) corrected serum calcium level <7.0 mg/dL at the start of the washout period (week –2), or ≥11.0 mg/dL at the end of the washout (week 0); and (3) serum intact parathyroid hormone (PTH) ≥1000 pg/mL at the start of the washout period (week –2). Chewable lanthanum carbonate was administered to CAPD patients for a period of 8 weeks, three times daily immediately after each meal, with or without a little water. All subjects received an initial dose of 750 mg/ day. Depending on the observed efficacy (serum phosphate levels) and safety (incidence of adverse events, etc.), the dose was increased or decreased by a unit of 750 mg/day 2 weeks after administration of each dose, to a maximum dose of 2250 mg/day. The therapeutic target for the maintenance of serum phosphate level was set at ≤5.5 mg/dL, with a dose reduction to be considered when the level fell below 3.0 mg/dL. Control of serum phosphate was the primary efficacy assessment. Levels of serum calcium, calcium × phosphate product (Ca×P), and intact PTH as well as adverse events were also evaluated. A total of 45 subjects at 11 centers met the criteria for entry into the treatment period. All 45 subjects received at least one dose of the study drug and were included in the safety analysis. Concerning dose, the dosing profile of lanthanum carbonate became relatively constant during the last 4 weeks, and at week 8, the proportions of the subjects on 750 mg, 1500 mg, and 2250 mg were 32%, 45%, and 24 %, respectively. By the end of the study period, 75% of the patients had achieved a serum phosphate level of ≤5.5 mg/dL. Serum phosphate level was reduced by 1.41 mg/dL [95% confidence interval (CI): –1.85 to –0.97] by week 4 and by 1.70 mg/dL (95% CI: –2.19 to –1.21) by week 8. Importantly, mean change from baseline at week 8 was –1.15 mg/dL (95% CI: –1.51 to –0.79) in the subgroup with baseline values <8 mg/dL and, in the subgroup with baseline value ≥8 mg/dL, –2.9 mg/dL (95% CI: –4.17 to –1.63) (Table 1). Thus, more significant changes were observed in subjects with higher baseline values. The