Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial

Abstract

Background and objectives: Lanthanum carbonate (FOSRENOL, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis.

Design, setting, participants and measurements: A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized (2:1) to lanthanum carbonate or placebo (80 versus 41). The modified intent-to-treat population included 90 patients (56 versus 34); 71 (43 versus 28) completed the study. After run-in, when any current phosphate binders were discontinued and dietary counseling reinforced, patients with serum phosphorus >4.6 mg/dl received lanthanum carbonate (titrated up to 3000 mg/d) or matching placebo for 8 wk.

Results: At the end of treatment, 25 (44.6%) versus nine (26.5%) patients had serum phosphorus < or =4.6 mg/dl (difference 18.1%, P = 0.12) in the lanthanum carbonate and placebo groups, respectively. Statistically significant differences were observed between groups in change from baseline to end of treatment for serum phosphorus (P = 0.02), intact parathyroid hormone (P = 0.02), and urinary phosphorus excretion (P = 0.04). The safety profile and tolerability of lanthanum carbonate were similar to that of placebo.

Conclusions: Because <1% of phosphorus is in the extracellular fluid, serum measurements may not accurately reflect total body burden in patients with CKD stages 3 and 4. However, lanthanum carbonate is an effective phosphate binder in this patient population, with a safety profile and tolerability similar to that of placebo.

Trial registration: ClinicalTrials.gov NCT00234702.

Figure 1.

Study design and patient disposition. *Patients with serum phosphorus ≤4.6 mg/dl (1.49 mmol/L) or serum calcium <8.0 mg/dl (2.0 mmol/L) at the baseline visit were withdrawn from the study and excluded from the modified intent-to-treat (ITT) population. Serum P_i, serum phosphorus. To convert mg/dl to mmol/L, multiply by 0.323. Serum Ca, serum calcium. To convert mg/dl to mmol/L, multiply by 0.25. eGFR, estimated glomerular filtration rate.

Figure 2.

Percentage of patients (95% CI) achieving serum phosphorus concentrations ≤4.6 mg/dl during 8 wk of double-blind treatment with lanthanum carbonate (LC) or placebo. Observed-case and end of treatment (EOT) data are shown. CI, confidence intervals. Nine patients had serum phosphorus concentrations ≤4.6 mg/dl (1.49 mmol/L) at baseline. Six of these patients (five lanthanum carbonate and one placebo) failed the baseline visit criteria of serum phosphorus (>4.6 mg/dl) but had a postdose efficacy assessment and were therefore included in the modified intent-to-treat population. Another three patients (one lanthanum carbonate and two placebo) failed the baseline visit criteria of serum phosphorus (>4.6 mg/dl) but were granted waivers to continue in the study.

Figure 3.

Change from baseline in serum phosphorus concentrations during 8 wk of lanthanum carbonate (LC) or placebo treatment. Data are least squares mean ± SEM. Observed-case and end-of-treatment (EOT) data are shown. *P < 0.05 between treatments, analysis of covariance (ANCOVA) model. To convert mg/dl to mmol/L, multiply by 0.323.

Figure 4.

Change from baseline in intact parathyroid hormone (iPTH) concentrations during 8 wk of lanthanum carbonate (LC) or placebo treatment. Data are least squares mean ± SEM. Observed-case and end-of-treatment (EOT) data are shown. *P < 0.05 between treatments, analysis of covariance (ANCOVA) model. To convert pg/ml to ng/L, multiply by 1.0.

Figure 5.

Change from baseline in urinary phosphorus excretion during 8 wk of lanthanum carbonate (LC) or placebo treatment. Data are least squares mean ± SEM. Observed-case and end-of- treatment (EOT) data are shown. *P < 0.05 between treatments, analysis of covariance (ANCOVA) model. To convert mg/d to mmol/d, divide by 31.