BINDREN Film-coated tablet Ref.[50321] Active ingredients: Colestilan

BindRen contains colestilan. Colestilan is a non-absorbed, non-calcium, non-metallic phosphate-binding polymer. The binding sites become partially protonated in the stomach and interact through ionic and hydrogen bonding with both dietary phosphate anions and bile acids in the duodenum. By binding phosphate from food in the digestive tract, colestilan lowers the serum phosphorus concentration. Colestilan also binds bile acids, thereby lowering the serum LDL-cholesterol concentration. Changes in the bile acid pool in the gastrointestinal tract have also been observed to lower serum glucose. Colestilan may also bind uric acid in the gastrointestinal tract.

Three Phase III studies and two long term follow-up studies have been performed in patients with CKD Stage 5 on dialysis, in order to investigate efficacy and safety in this population.

Serum phosphorus

Fixed-dose study

In a double-blind, 12-week fixed-dose study with five colestilan groups (3, 6, 9, 12 and 15 g/day) and placebo, colestilan at 6 g/day and above demonstrated a dose-dependent reduction in serum phosphorus level. The least squares mean reduction from baseline to week 12 as compared to placebo was 0.16, 0.21, 0.19 and 0.37 mmol/L at 6, 9, 12 and 15 g/day respectively.

Flexible-dose studies

Two similar 12-week, open-label, flexible-dose studies followed by a 4-week double-blind withdrawal period (comparison to placebo) were performed. In the first study, the mean serum phosphorus level was 2.33 mmol/L at baseline and 1.96 mmol/L (mean reduction by 0.36 mmol/L) at week 12 on a colestilan mean daily dose of 11.5 g. Similarly in the second study, the mean serum phosphorus level was 2.44 mmol/L at baseline and 1.94 mmol/L at week 12 (mean reduction by 0.50 mmol/L) on a colestilan mean daily dose of 13.1 g. The rate of responders (either a reduction in serum phosphorus ≤1.78 mmol/L and/or a reduction from baseline ≥0.3 mmol/L) was 50.4 % and 43.8% in the two studies, respectively (placebo 30.8% and 26.3%, respectively).

Long-term studies

Two long-term, open-label, flexible-dose studies demonstrated that serum phosphorus reduction was maintained for up to one year. After one year, the mean serum phosphorus level was 1.89 mmol/L with a significant reduction from baseline of 0.39 mmol/L and responder rate (phosphorus level <1.78 mmol/L) was 44%. A majority of patients received 12 or 15 g/day of colestilan in the long-term studies.

Serum calcium

In clinical studies, colestilan had no effect on serum calcium levels over a period of up to one year.

Serum calcium-phosphorus ion product

Calcium-phosphorus ion product was reduced by at least 0.48 mmol²/L² at week 12 compared to placebo at doses ≥9 g/day in fixed-dose study and by 1.05 and 0.86 mmol²/L² at week 12 in two flexible-dose studies. Colestilan reduced calcium-phosphorus ion product by 0.90 mmol²/L² after one year.

Serum parathyroid hormone (PTH)

In most clinical studies, colestilan decreased serum PTH compared to baseline, and was statistically significant against placebo.

Serum cholesterol

Colestilan significantly reduced serum LDL-cholesterol by 17.8, 25.6, 29.4, 34.8 and 33.4% at 3, 6, 9, 12 and 15 g/day at week 12 compared to placebo in fixed-dose study, respectively. Colestilan also showed significant reductions from baseline by 35.3 and 30.1% at week 12 in two flexible-dose studies, and by 25.8% after one year in long-term studies. The reductions in LDL-cholesterol are also reflected in significant falls in total cholesterol.

Serum glycosylated haemoglobin A1c

In subjects with baseline HbA1c ≥7.0%, colestilan showed a reduction of between 0.36 to 1.38% at week 12 in the fixed-dose study, and by 0.94 and 0.91% at week 12 in the two flexible-dose studies. After one year of treatment, a reduction of 1.12% in HbA1c was observed.

Serum uric acid

Colestilan was also associated in dose-dependent reduction in serum uric acid, with a mean reduction of 43 micromol/L after one year of treatment.