ant 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.
5.2 Pharmacokinetic properties
BindRen is not absorbed from the gastrointestinal tract of healthy volunteers following oral administration of 14C-radiolabelled colestilan.
The results of in vitro testing suggest that medicinal products with anionic and/or lipophilic characteristics have a higher potential to bind to BindRen.
5.3 Preclinical safety data
Non-clinical data reveal no direct special hazard for humans based on conventional studies of safety pharmacology, single- and repeated-dose toxicity, genotoxicity, carcinogenic potential or toxicity to reproduction and development. However, reproductive toxicity studies were not conducted at doses higher than 2.5 times the human clinical dose, and the possible reproductive effects related to coagulation and bleeding have not been assessed.
Haemorrhage and increased clotting parameters (PT and aPTT) were evident in rats following repeat administration. These were considered to result from a deficiency of vitamin K following a reduction in the absorption of fat-soluble vitamins (see section 4.4).
6. Pharmaceutical particulars
6.1 List of excipients
Tablet core
Purified water
Hydroxypropylcellulose
Silica, colloidal anhydrous
Castor oil, hydrogenated
Film-coating
Hypromellose
Acetic acid esters of mono- and diglycerides of fatty acids
Polysorbate 80
Printing ink
Shellac
Indigo carmine aluminium lake (E 132)
Carnauba wax
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years
6.4 Special precautions for storage
This medicinal
