An open-label randomized Phase II study of PA21 compared to sevelamer to evaluate the ability of PA21 to control serum phosphate levels and the tolerability in patients with chronic kidney disease undergoing hemodialysis

• Conditions: patients with chronic kidney disease undergoing hemodialysishyperphosphatemia; MedDRA version: 9.1Level: LLTClassification code 10020712Term: Hyperphosphatemia

• Registration Number: EUCTR2007-003565-40-DE
• Lead Sponsor: Vifor (International) Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-02
• Last Update Posted: 10 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

Inclusion Criteria at Screening
Patients will be entered into this study only if they meet all of the following criteria, at screening:
1. =18 years of age,
2. Receiving maintenance hemodialysis 3 times a week for =3 months,
3. Receiving stable doses of phosphate binder for at least 1 month before screening (with or without vitamin D or vitamin D metabolite therapy). Patients receiving vitamin D therapy must remain on the same dose throughout the study,
4. Having stable calcium content in dialysate,
5. Able to read and write with sufficient competence to understand the study procedures and capable of giving legal consent,
6. Able to provide written informed consent.

Inclusion Criteria for Entry into the Treatment Period
To be eligible for randomization and to enter into the treatment period, the patients must meet the following serum phosphate level condition either after 1 week of washout or at the end of the allowed 2-week washout period:
7. Having serum phosphate levels >1.76 mmol/L (5.5 mg/dL) and =3.0 mmol/L (9.3 mg/dL) after a washout period for previous phosphate binders (up to 2 weeks).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Uncontrolled hyperphosphatemia (>2.5 mmol/L) while on conventional phosphate binders (value at screening),
2. Serum phosphate >3.0 mmol/L after the start of washout,
3. Hypercalcemia (serum calcium >2.5 mmol/L) at screening or during washout,
4. Serum calcium < 1.9 mmol/L at screening or during washout,
5. Severe hyperparathyroidism (iPTH levels >800 ng/L),
6. History of parathyroidectomy,
7. Intention to initiate therapy with vitamin D, vitamin D metabolites or calcimimetics during the study,
8. Non-stable therapy with vitamin D, vitamin D metabolites or calcimimetics (if applicable),
9. Known to be non-responder to phosphate binders,
10. Known hypersensitivity to PA21, sevelamer (as Renagel®), or to any of their excipients, or iron allergy,
11. Pregnancy or lactation,
12. Lack of highly effective contraception in female patients of child-bearing potential:
This excludes any female patient who is not currently using or is not willing to continue to use a highly effective method of birth control ie, implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence, unless she is surgically sterilized (tubal ligation and/or hysterectomy), post-menopausal (amenorrhea for at least 1 year before screening) or has a vasectomized partner
13. Significant gastrointestinal disorder (including known active peptic ulcer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, motility disorder of the intestines [symptomatic gastroparesis {treated or untreated}, ileus, pseudo-obstruction, megacolon, or mechanical obstruction] and history of major gastrointestinal surgery),
14. Hepatitis B (hepatitis B surface antigen [HBsAg] positivity only), hepatitis C (hepatitis C virus ribonucleic acid [HCV RNA] positivity only) or other significant concurrent liver disorders (alanine transaminase [ALT] or aspartate transaminase [AST] >3 times the upper limit of the normal range),
15. Intention to change diet during the study,
16. Known or suspected non-compliance with dietary phosphate restrictions,
17. Known infection with human immunodeficiency virus (HIV),
18. History of drug or alcohol abuse within 2 years before screening,
19. Use of antacids containing aluminum or magnesium within 1 month before screening,
20. Serious medical condition, uncontrolled systemic disease (eg, poorly controlled diabetes mellitus, hypertension, active malignant disease within the last 5 years [except non-melanotic skin cancer] planned surgery including kidney transplantation during study, or suspected life-expectancy of <12 months per Investigator’s assessment),
21. Inability to fully comprehend and/or perform study procedures (in the Investigator’s opinion),
22. Receipt of any other investigational drug <30 days before the study or during the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate non-inferiority, and if possible superiority of PA21 compared to sevelamer in terms of the ability to control serum phosphate levels after 8 weeks of treatment in patients with chronic kidney disease undergoing hemodialysis. ;Secondary Objective: - To evaluate the time required to reach the first controlled serum phosphate levels,<br>- To evaluate the effect of PA21 compared to sevelamer on serum calcium levels, on serum calcium x phosphate product and intact parathyroid hormone (iPTH) levels,<br>- To evaluate the tolerability and safety of PA21 compared to sevelamer.<br>;Primary end point(s): Achievement of controlled serum phosphate levels (ie, between 1.13 and 1.76 mmol/L, inclusive) at the end of treatment period.