Evaluation of colestilan in chronic kidney disease dialysis patients with hyperphosphataemia and dyslipidaemia: a randomized, placebo-controlled, multiple fixed-dose trial

Abstract

Background: Colestilan is a non-absorbed, non-calcium-based, phosphate binder. It also binds bile acids and reduces serum levels of low-density lipoprotein cholesterol (LDL-C). This study evaluated the efficacy of a range of fixed doses of colestilan compared with placebo for the control of serum phosphorus and LDL-C levels in patients with CKD stage 5 on dialysis.

Methods: This was a multicentre, randomized, double-blind, placebo-controlled, multiple fixed-dose trial in which 642 patients with CKD stage 5 on dialysis who had both hyperphosphataemia and dyslipidaemia, were randomized to treatment with colestilan 3, 6, 9, 12 or 15 g/day or placebo for 12 weeks. The co-primary endpoints were the mean changes in serum phosphorus and the mean per cent change in LDL-C from baseline to Week 12.

Results: A significantly greater mean reduction in serum phosphorus level from baseline to Week 12 than seen with placebo was seen with 9 g (-0.28 mmol/L) and pooled colestilan 12/15 g (-0.34 mmol/L). The per cent reduction in LDL-C level was significantly greater with colestilan 3, 6 and 9 g and pooled colestilan 12/15 g than with placebo (reduction ranged from 15.9 to 27.6% dependent on dose). Colestilan also reduced total cholesterol, oxidized LDL-C, HbA1c and uric acid levels, and did not increase serum calcium levels. Colestilan was generally well tolerated; the most common adverse events affected the gastrointestinal system.

Conclusions: Colestilan is an effective treatment for hyperphosphataemia, and provides beneficial effects on other metabolic parameters associated with cardiovascular risk, notably LDL-C.

Keywords: MCI-196; chronic kidney disease; colestilan; dyslipidaemia; hyperphosphataemia.