A 12-week, open label, multicenter, titration study, with a 9-month maintenance treatment extension, to demonstrate efficacy of SBR759 compared to sevelamer HCl in lowering serum phosphate levels in Chronic Kidney Disease patients on hemodialysis

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2006-001787-23-FR
• Date of registration: 06/06/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 12-week, open label, multicenter, titration study, with a 9-month maintenance treatment extension, to demonstrate efficacy of SBR759 compared to sevelamer HCl in lowering serum phosphate levels in Chronic Kidney Disease patients on hemodialysis
• Scientific title: A 12-week, open label, multicenter, titration study, with a 9-month maintenance treatment extension, to demonstrate efficacy of SBR759 compared to sevelamer HCl in lowering serum phosphate levels in Chronic Kidney Disease patients on hemodialysis
• Date of first enrolment: 04/08/2008
• Target sample size: 378
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001787-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Stratified per serum phosphorus levels (= to 75.mg/dL) If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Estonia, Finland, France, Germany, Italy, Latvia, Lithuania, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must give written informed consent before any assessment is performed.
2. Men or women of at least 18 years old.
3. Patient must be treated with a stable maintenance hemodialysis (i.e. no change in dialysis material and parameters) 3 times per week for > 3 months before screening and planned to be maintained the same throughout the study duration.
4. Patient must be on restricted phosphate diet at screening and throughout the study.
5. Patient has a controlled serum phosphate > 3.0 mg/dL (> 0.97 mmol/L) and < 6.0 mg/dL (< 1.9 mmol/L), as indicated by the average of the 2 latest pre-dialysis laboratory values reported prior to screening, if currently under phosphate binder therapy.
6. Patient has a serum phosphate level > 6.0 mg/dL (> 1.9 mmol/L), obtained from central laboratory, prior to study treatment initiation.
7. Patient must have a Urea Reduction Ratio of > 65% (obtained within 2 weeks prior to screening).
8. If patient has a history of parathyroidectomy, iPTH and calcium-phosphate product levels should be stable within 30 days prior to screening.
9. Patient must be on a stable phosphate binder dose (i.e. No change in prescribed dose) for at least 30 days prior to screening, or is newly diagnosed with hyperphosphatemia and has not initiated treatment with phosphate binder yet.
10. Patient must, in the investigator’s opinion, be compliant with prescribed phosphate binders.
11. If patient is currently being treated with calcimimetics, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
12. If patient is currently being treated with vitamin D, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
13. If patient is currently being treated with IV iron, the prescribed dose must be constant for at least 30 days prior to screening and should remain constant during the total core study duration.
14. If patient is currently being treated for osteoporosis, the prescribed dose must be constant for at least 30 days prior to screening and during the total core study duration.

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. Patient is on peritoneal dialysis or a non-conventional hemodialysis technique (e.g.
hemofiltration, hemodiafiltration)
2. Patient has a parathyroidectomy or transplant scheduled during the study.
3. Patient has an uncontrolled hyperparathyroidism (i.e. intact PTH > 800 pg/mL within 30 days prior to study screening)
4. Patient has a history of hemochromatosis or ferritin > 800 µg/L.
5. Patient has a clinically significant GI disorder (i.e. swallowing disorder, active dysphagia, bowel obstruction, severe GI motility disorder)
6. Patient has a chronic unstable GI disorder (e.g. Irritable Bowel Syndrome, Inflammatory Bowel Disease, chronic abdominal pain, chronic diarrhea)
7. Patient has an history of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection.
8. Patient has a clinically significant unstable medical condition (e.g. uncontrolled diabetes, etc.), other than Chronic Kidney Disease.
9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
10. Patient is known to currently have a drug or alcohol abuse problem.
11. Patient has a known history of immunodeficiency disease, e.g. existing positive HIV (ELISA or Western blot) test result.
12. Patient is / has been treated with sevelamer HCl monotherapy or SBR759 within 3 months prior to screening.
13. History of intolerance to sevelamer HCl.
14. Patient is currently being treated with oral iron.
15. Patient currently has an active infection or is being treated with antibiotics (within 14 days prior to screening).
16. Patient currently has an active antiviral treatment for Hepatitis B and/or C (within 30 days prior to screening).
17. Patient is currently being treated with anti-seizure medications for the control of a seizure disorder (i.e. phenobarbital, valproate, carbamazepine)
18. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives of enrollment, whichever is longer
19. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
20. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation
21. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant. UNLESS they are using a highly effective method of birth control
(i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some
intrauterine devices (IUDs). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hyperphosphataemia in patients with Chronic Kidney Disease (CKD) on hemodialysis
MedDRA version: 9.1 Level: LLT Classification code 10020712 Term: Hyperphosphatemia

Intervention(s)

Product Name: SBR759
Product Code: SBR759
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: not yet established
Current Sponsor code: SBR759-NXA 001
Other descriptive name: Fe(OH)+ Starch + saccharose complex
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000 mg -

Product Name: SBR759
Product Code: SBR759
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: not yet established
Current Sponsor code: SBR759-NXA 001
Other descriptive name: Fe(OH)+ Starch + saccharose complex
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1500 mg-

Trade Name: Renagel
Product Name: RENAGEL
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sevelamer hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 800mg-

Primary Outcome(s)

Secondary Objective: To evaluate safety and tolerability of SBR759 compared to sevelamer HCl over a 12-week period.
To evaluate whether SBR759 has superior efficacy at week 12 compared to sevelamer HCl, as measured by the number of patients with a serum calcium-phosphate product levels below or equal to 55 mg2/dL2.
to evaluate whether SBR759 is associated with less increase in serum iPTH levels compared to sevelamer HCl at 12 weeks
to evaluate whether SBR759 has an equivalent rate of hypercalcemia events at 12 weeks compared to sevelamer HCl as measured by serum calcium levels
to evaluate changes in patient-reported gasrointestinal symptom burden, using gastrointestinal symptom rating scale (GSRS) total and subscales scores, in patients treated with SBR759 compared to patients treated with sevelamer HCl

Main Objective: This study is designed to demonstrate superior or at least non-inferior
efficacy of SBR759 in phoshate binding, versus sevelamer HCl and evaluate safety over a long term exposure. Efficacy will be measured by the number of patients with a serum phosphate level below or equal to 5.5 mg/dl (i.e. 1.78 mmol/L) at 12 weeks

Primary end point(s): To demonstrate superior efficacy or at least non-inferiority of SBR759 compared to sevelamer HCl, as measured by the number of patients with a serum phosphate level below or equal to 5.5 mg/dl (i.e. 1.78 mmol/L) at 12 weeks.

Secondary ID(s)

CSBR759A2201