Phase III Study to Investigate the Safety and Efficacy of Fermagate and Sevelamer Hydrochloride

An Open, Randomised, Controlled, Parallel Group, Phase III Study to Investigate the Safety and Efficacy of Fermagate and Sevelamer Hydrochloride in Haemodialysis Patients With Hyperphosphataemia

Magnesium iron hydroxycarbonate is a phosphate binder that absorbs phosphate from food, reducing the amount that the body can absorb.

The purpose of this study is to assess the efficacy of magnesium iron hydroxycarbonate in subjects requiring haemodialysis, compared with a marketed phosphate binder, sevelamer hydrochloride.

High levels of phosphate in the blood are linked with serious effects, due to calcium imbalances (high levels of parathyroid hormone (PTH), bone disease, formation of calcium deposites in the body and blood-vessel disease.

Current guidelines indicate that blood phosphorous levels should be maintained between 1.13 to 1.78mmol/L in patients who receive haemodialysis.

The purpose of this study is to establish the non-inferiority of magnesium iron hydroxycarbonate to sevelamer hydrochloride in lowering serum phosphate in haemodialysis patients treated for 3 months. Additional objectives: (1) to determine the safety of magnesium iron hydroxycarbonate after short term (3 months) and long term (6 and 12 months) treatment, (2)to determine the efficacy of magnesium iron hydroxycarbonate after long term treatment (6 and 12 months) and (3) To compare the effects of magnesium iron hydroxycarbonate and sevelamer hydrochloride on measures of mineral metabolism, albumin, pre-albumin and iron status after short term (3 months) and long term (6 and 12 months) treatment.

Inclusion Criteria:

Subjects will be considered eligible for entry in the study if they meet all of the following criteria.

1. Male or female, aged > 18 years.

2. Able to comply with the study procedures and medication.

3. Written informed consent given.

4. On a stable haemodialysis regimen (at least 3x per week) for ≥12 weeks prior to screening.

5. (a) Subject receiving phosphate binder medication(s) at screening, must have been on a stable regimen (dose and medication) for at least 1 month prior to screening and will remain on this regimen until entry into the washout period OR (b)Subject (i) is not currently receiving any phosphate binding medication at screening (or medication likely to act as a phosphate binder) and (ii) must not have done so for at least one month and (iii) has sustained hyperphosphataemia.

6. Willing to abstain from taking any phosphate binder or oral magnesium-, oral aluminium- or oral iron-containing products and preparations other than the study medication.

7. If required to take >6000 mg/day of fermagate, the subject will be willing to have at least three meals per day.

   Specifically, for randomisation and inclusion into the treatment period, the following criterion must be fulfilled:

8. Has a serum phosphate value of ≥1.94 mmol/L (≥6.0 mg/dL) within the 2 to 4 week washout period or above 3.0 mmol/L (9.3 mg/dL) at any time during washout.

Exclusion Criteria:

Subjects will not be considered eligible for entry in the study if they meet one or more of the following criteria.

1. Participation in any clinical trial using an investigational product or device during the 30 days preceding the Screening Visit.
2. Previous experience of fermagate treatment.
3. A significant history of alcohol, drug or solvent abuse in the opinion of the investigator.
4. Any disease or condition, physical or psychological that, in the opinion of the investigator, would compromise the safety of the subject or the likelihood of achieving reliable results or increase the likelihood of the subject being withdrawn.
5. Laboratory findings at screening which, in the opinion of the investigator, are clinically significant for this subject population.
6. A screen serum magnesium concentration of >1.25 mmol/L (>3.0 mg/dL).
7. A known history of haemochromatosis.
8. Subjects receiving either tetracycline or lithium treatment.
9. A serum ferritin level of ≥1000 ng/mL.
10. Non-elective hospitalisation in the 4 weeks prior to screening.
11. Female subjects who are of childbearing potential and who are neither surgically sterilised nor using reliable contraceptive methods (hormonal, barrier methods or intrauterine device) or who are lactating or pregnant.
12. Current hypophosphataemia at screening (last 2 consecutive phosphate values of <0.7 mmol/L [<2.2 mg/dL]).
13. Known history of colorectal malignancy, familial polyposis coli and/or strong family history (in 2 or more first degree relatives) of these terms.
14. A QTcF interval of >560 ms at screen.
15. Known persistent (>1 month) non compliance (<70%) with prescribed medication regimens at screen.
16. Current clinically significant intestinal motility disorder.
17. Bowel obstruction with current or previous use of sevelamer HCl.
18. Known intolerance to sevelamer HCl or any excipients of fermagate or Renagel medication.
19. Subjects with inflammatory bowel disease that, in the investigator's opinion, is poorly controlled.