Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia.
BACKGROUND
Lanthanum carbonate is a novel, non-calcium, non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis.


METHODS
This 16-week study assessed the control of serum phosphorus with lanthanum carbonate, and its effects on serum calcium, calcium x phosphorus product, and parathyroid hormone (PTH). Hemodialysis patients > or =18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to >5.9 mg/dL (1.90 mmol/L). In total, 126 patients were titrated with lanthanum carbonate at doses containing 375, 750, 1,500, 2,250, or 3,000 mg/d elemental lanthanum, given in divided doses with meals over a 6-week period, to achieve serum levels < or =5.9 mg/dL. By the end of dose titration, 11/126 (9%) patients received < or =750 mg/d of lanthanum, 25 (20%) received 1,500 mg/d, 37 (29%) received 2,250 mg/d, and 53 (42%) received 3,000 mg/d. Following titration, patients were randomized to receive either lanthanum carbonate or placebo during a 4-week, double-blind maintenance phase.


RESULTS
At the study endpoint, the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL (0.62 mmol/L) (P < 0.0001). Calcium x phosphorus product (P < 0.0001) and serum PTH levels (P < 0.01) were also significantly lower with lanthanum carbonate versus placebo. The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients.


CONCLUSIONS
Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD.
Joy
Melanie S
MS
University of North Carolina, School of Medicine, Division of Nephrology and Hypertension,Chapel Hill, NC 27599-7155, USA. Melanie_Joy@med.unc.edu
Finn
William F
WF
D000368:Aged; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D007811:Lanthanum / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010281:Parathyroid Hormone / Q000097:blood; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010710:Phosphates / Q000097:blood* / Q000493:pharmacokinetics; D006435:Renal Dialysis; D012449:Safety; D016896:Treatment Outcome
D010281:Parathyroid Hormone; D010710:Phosphates; C119467:lanthanum carbonate; D007811:Lanthanum; D002118:Calcium