Phosphate binder now comes in 1000 mg tablet, reducing intake burden for dialysis patients.

SAN DIEGO—Doses of lanthanum carbonate as high as 4,500 mg a day appear to be well tolerated and may provide serum phosphorus control for some stage-5 CKD patients who do not respond to 3,000 mg a day, according to a new trial of patients on maintenance hemodialysis.

“This is the first time a study has looked at a higher dose of lanthanum carbonate, and we found that a larger proportion of patients have controlled phosphorous levels without an increase in adverse events,” said lead investigator Rajnish Mehrotra, MD, associate professor of medicine in the division of nephrology and hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, in Torrance, Calif.

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While hyperphosphatemia is associated with increased morbidity and mortality in stage-5 CKD patients, studies have suggested that most such patients on dialysis do not achieve the serum phosphorous targets of 3.5-5.5 mg/dL recommended by the Kidney Disease Outcomes Quality Initiative (K/DOQI). Failure to achieve target levels is partly due to poor patient adherence to phosphate-binder therapy, Dr. Mehrotra said. Patients must take up to 17 pills a day.

A noncalcium phosphate binder, lanthanum carbonate (LC) has been formulated to provide reduced tablet size and increased dosage strengths (750 and 1,000 mg) to decrease the high pill burden. Dr. Mehrotra’s team assessed the efficacy of LC at doses of 3,000-4,500 mg a day in patients who were not adequately controlled at doses of 3,000 mg a day or less.

Researchers at 65 U.S. sites enrolled a total of 513 patients with a mean age of 54.9 years and a mean dialysis time of 3.9 years; 63% were men, 48% African-American, and 50% diabetic. Dr. Mehrotra, who presented the findings at the 39th annual meeting of the American Society of Nephrology here, said that following a 0-to-3-week wash-out from previous binders, all the patients began a three-part LC treatment: (1) a four-week open-label titration period; (2) continued participation in an open-label phase for those reaching K/DOQI target or; (3) a four-week, double-blind, forced-dose titration phase for patients not at target (randomized to 3,000, 3,750, or 4,500 mg a day of LC). There was a 16-week open-label extension for all patients.

After four weeks, 54% of the patients achieved the target range for se-rum phosphorus, with a mean change of 2.18 mg/dL from baseline. These 215 patients entered cohort A. Their mean serum phosphorus remained 5.5. mg/dL or less through week 24. Patients not at target for serum phosphorus at week four (cohort B; n=142) were found to have a dose-dependent change in serum phosphorus of 0.59 mg/dL (3,750 mg a day) and 0.76 mg/dL (4,500 mg a day) by week eight.

By week eight, the serum phosphorus target was achieved in 37% of the those receiving 3,750 or 4,500 mg a day of LC. The most common side effects were nausea and vomiting, as well as diarrhea and constipation. They were not dose-related, and the higher dose did not in-crease the incidence of adverse events.

The mean levels of correct serum calcium parathyroid hormone (until week 24) and calcium phosphorous product (after week four) remained within K/DOQI guidelines, Dr. Mehrotra reported. Liver enzymes (ALT, AST, and GGT) remained within normal clinical ranges throughout the study period.

The researchers found that the 750 mg and 1,000 mg tablets of LC made a simplified regimen possible—one tab-let at each meal, for a total of three a day. The investigators theorize that this reduction in pill burden will increase patient adherence and improve serum phosphorus control.