An investigational calcium-free phosphate binder called colestilan is safe and effective for controlling phosphorus in dialysis patients, and it has no impact on calcium levels, researchers reported.
Treatment with the novel binder also was associated with clinically relevant decreases from baseline in calcium × phosphorus product and significant declines in low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (A1c), and parathyroid hormone (PTH).
In an open-label phase following a one- to five-week phosphate-binder washout, dialysis patients received colestilan at a dosage of 3-15 g/day, with dose-titration allowed to achieve a target phosphorus level of 3.5-5.5 mg/dL. During the open-label phase, colestilan significantly decreased phosphorus levels by 1.54 mg/dL from baseline to week 12. Colestilan decreased mean LDL-C by 30.1% and mean A1c by 0.91% in patients with an A1C of 7% or higher (mean 8.5%).
After 12 weeks, the investigators, led by Joachim E. Hertel, MD, of Nephrology Associates in Augusta, Ga., randomized subjects to receive colestilan (85 patients) or placebo (83 patients) for four weeks. Compared with placebo, colestilan-treated patients had a mean 1.01 mg/dL decrease in phosphorus from week 12 to week 16. Patients with baseline phosphorus levels of 7.5 mg/dL or higher (mean 8.76 mg/dL) showed a mean decrease of 2.41 mg/dL versus placebo.
In addition, compared with placebo, colestilan was associated with a significant 51.9 mg/dL mean decrease in LDL-C, a mean 7.91 decrease in calcium × phosphorus product, a mean 0.28% decrease in A1c, and a mean 66.6 pg/mL decrease in PTH. The investigators observed no significant difference in calcium levels between the treatment arms.
The most frequently reported treatment-emergent adverse events during the open-label phase included nausea (9% of patients), diarrhea (9%), vomiting (7.8%), and constipation (6.1%), the investigators noted. During the placebo-controlled phase, nausea, diarrhea, and vomiting occurred in 4.7%, 3.5%, and 3.5% of the colestilan group compared with 0%, 3.6%, and 0%, respectively, of the placebo recipients.