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.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Failure
• Intervention / Treatment: Drug: Fermagate; Drug: Sevelamer hydrochloride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • O.L.V Ziekenhuis
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Jette, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Leuven, Belgium, 3000
    • U. Z. Gasthuisberg
  • Liège, Belgium, 4000
    • Hôpital de la Citadelle
• Brazil
  • MG
    • Uberlandia, MG, Brazil
      • Nefroclinica de Uberlandia Ltda
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21041-030
      • Hospital Geral de Bonsucesso
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
• Bulgaria
  • Pazardzhik, Bulgaria, 4400
    • MHAT - Pazardzhik AD
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment "Dr. G. Stransky"
  • Plovdiv, Bulgaria, 4002
    • MHAT - Plovdiv AD
  • Rousse, Bulgaria, 7002
    • MHAT - Rousse AD
  • Sofia, Bulgaria, 1407
    • MHAT 'Tokuda Hospital Sofia' AD
  • Sofia, Bulgaria, 1431
    • UMHAT 'Alexandrovska'
  • Sofia, Bulgaria, 1431
    • UMHAT 'Sv. Ivan Rilski' EAD
  • Sofia, Bulgaria, 1606
    • Multiprofile Hospital for Active Treatment and Emergency Medicine "Pirogov"
  • Varna, Bulgaria, 9002
    • MHAT 'Sv. Anna - Varna' AD
  • Varna, Bulgaria, 9010
    • MHAT 'Sveta Marina'
  • Veliko Tarnovo, Bulgaria, 5000
    • Centre of Haemodialysis and Nephrology MHAT 'Dr. Stefan Cherkezov' AD
• Czech Republic
  • Brno, Czech Republic, 65691
    • Fakultni nemocnice u sv. Anny
  • Liberec, Czech Republic, 46063
    • Krajska nemocnice Liberec, a.s.
  • Prachatice, Czech Republic, 38320
    • Nemocnice v Prachaticich, a.s.
  • Praha 6, Czech Republic, 169 00
    • VFN Praha
  • Tabor, Czech Republic, 39003
    • Nemocnice Tabor a.s.
  • Znojmo, Czech Republic, 66902
    • Nemocnice Znojmo
• Estonia
  • Tallinn, Estonia, 10617
    • West-Tallinn Central Hospital
  • Tallinn, Estonia, 13419
    • North Estonia Regional Hospital
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• Hungary
  • Budapest, Hungary, 1037
    • FMC Dialysis Centre
  • Hodmezovasarhely, Hungary, 6800
    • Diaverum Dialysis Centre
  • Kecskemet, Hungary, 6000
    • FMC Dializis Center Kecskemet
  • Vác, Hungary, 2600
    • FMC Dializis Centrum Kft Vac Javorszky Odon Korhaz
• Israel
  • Ashkelon, Israel, 78306
    • Barzilai Medical Center
  • Beer Yaakov, Israel, 70300
    • Assaf Harofeh Medical Center
  • Naharia, Israel, 22100
    • Western Galilee Hospital - Nahariya
• Italy
  • CR
    • Cremona, CR, Italy, 26100
      • Azienda Ospedaliera Istituti Ospitalieri di Cremona
  • MO
    • Modena, MO, Italy, 41100
      • Azienda Ospedaliera Policlinico di Modena
  • PV
    • Pavia, PV, Italy, 27100
      • Fondazione "S. Maugeri" IRCCS
• Lithuania
  • Kaunas, Lithuania, 49476
    • Diaverum klinikos JSC
  • Kaunas, Lithuania, 50009
    • Kaunas Medical University Hospital Public Institution
  • Kaunas, Lithuania, 50169
    • B.Braun Avitum JSC
  • Kedainiai, Lithuania, 57164
    • Diaverum klinikos JSC
  • Klaipeda, Lithuania, 93220
    • Diaverum klinikos JSC
  • Siauliai, Lithuania, 76231
    • Siauliai Regional Hospital Public Institution
  • Vilnius, Lithuania, 03219
    • Diaverum klinikos JSC
  • Vilnius, Lithuania, 10207
    • Vilnius City University Hospital Public Institution
• Mexico
  • Monterrey, Mexico, 64000
    • Hospital y Clinica OCA SA de CV
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center Zvezdara
  • Nis, Serbia, 18000
    • Clinical Center Nis
  • Novi Sad, Serbia, 21000
    • Clinical Centre of Vojvodina
  • Zemun, Serbia, 11080
    • Clinical Center Zemun
• Slovakia
  • Banska Bystrica, Slovakia, 97517
    • LOGMAN a.s.
  • Levice, Slovakia, 93401
    • Nephro s.r.o. Levice
  • Martin, Slovakia, 03601
    • Privat Nephro-Dialysis Centre Ldt Martin
  • Trencin, Slovakia, 91171
    • LOGMAN a.s.
• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7460
      • N1 City Hospital
    • Cape Town, Western Cape, South Africa, 7800
      • South Peninsula Dialysis
    • Cape Town, Western Cape, South Africa, 7925
      • Grootte Schuur Hospital
    • Parow, Western Cape, South Africa, 7050
      • Panorama Medi Clinic
    • Parow, Western Cape, South Africa, 7500
      • Tygerberg Hospital
• United Kingdom
  • Reading, United Kingdom, RG1 5AN
    • Royal Berkshire Hospital
  • Sheffield, United Kingdom, S5 7AU
    • Northern General Hospital
  • Cambs
    • Cambridge, Cambs, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
  • Gt Lon
    • London, Gt Lon, United Kingdom, E1 1BB
      • The Royal London Hospital
  • Leics
    • Leicester, Leics, United Kingdom, LE5 4PW
      • Leicester General Hospital
  • Mersyd
    • Liverpool, Mersyd, United Kingdom, L7 8XP
      • Royal Liverpool Hospital
  • Norflk
    • Norwich, Norflk, United Kingdom, NR4 7UZ
      • Norfolk and Norwich University Hospital
  • Nthumb
    • Bradford, Nthumb, United Kingdom, BD5 0NA
      • St Lukes Hospital
  • S Glam
    • Cardiff, S Glam, United Kingdom, CF14 4XW
      • University Hospital of Wales
• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71901
      • Arkansas Nephrology Services Ltd
  • California
    • Bakersfield, California, United States, 93309
      • National Institute of Clinical Research
    • Lynwood, California, United States, 90262
      • Renal Medical Associates
    • Monterey Park, California, United States, 91754
      • Academic Medical Research Institute Inc
    • Pasadena, California, United States, 91105
      • Pasadena Nephrology
    • Porterville, California, United States, 93257
      • Sierra View Nephrology SC
    • Thousand oaks, California, United States, 91361
      • Kidney Center Inc.
  • Connecticut
    • Stamford, Connecticut, United States, 06902
      • Stanford Nephrology
  • District of Columbia
    • Washington, District of Columbia, United States, 20002
      • Capitol Dialysis
  • Florida
    • Ocala, Florida, United States, 34471
      • Discovery Medical Research Group Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Cleveland William MD
    • Brunswick, Georgia, United States, 31520
      • Davita South Brunswick Dialysis Center
  • Illinois
    • Evanston, Illinois, United States, 60201
      • North Shore University Health System
    • Evergreen Park, Illinois, United States, 60805
      • Southwest Nephrology Associates
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Renal Associates of Baton Rouge
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Western New England Transplant Associates
  • Michigan
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • Washington University School of Medicine
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Huq Cruz Strauss Masud PA
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Regional Medical Center
  • New York
    • Bellmore, New York, United States, 11710
      • Nassau Nephrology, LLP
    • Springfield Gardens, New York, United States, 11413
      • Clinical Research Development Associates LLC
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Nephrology Associates, PA
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Bayview Nephrology
    • Pittsburgh, Pennsylvania, United States, 15224
      • Renal Endocrine Associates PC
    • Pittsburgh, Pennsylvania, United States, 15224
      • Renal-Endocrine Associates
  • South Carolina
    • Aiken, South Carolina, United States, 29801
      • CSRA Renal Services
    • Sumter, South Carolina, United States, 29150
      • Carolina Diabetes & Kidney Center
    • Sumter, South Carolina, United States, 29150
      • Carolina Diabetes and Kidney Center/ sumter Medical Specialist
  • Texas
    • Arlington, Texas, United States, 76015
      • South Arlington Dialysis Center
    • Grand Prairie, Texas, United States, 75050
      • U.S Renal Care
    • Grand Prairie, Texas, United States, 75050
      • U.S. Renal Care
    • Houston, Texas, United States, 77004
      • Diagnostic Clinic of Houston
    • Houston, Texas, United States, 77099
      • SouthWest Houston Research LTD.
    • San Antonio, Texas, United States, 78215
      • Renal Associates PA
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Ramon Mendez MD PC (private practice)
    • Alexandria, Virginia, United States, 22304
      • Ramon Mendez, MD, PC (private practice)
    • Fairfax, Virginia, United States, 22030
      • Clinical Research & Consulting Center LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 2	Drug: Sevelamer hydrochloride; Tablet 800mg; Other Names: Renagel
EXPERIMENTAL: 1	Drug: Fermagate; Film coated tablet 500mg; Other Names: Alpharen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Control or not the level of serum phosphate	Within the treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in mean serum phosphate	End of 3 months treatment in maintenance period
Change from baseline in calcium, calcium phosphate product and PTH level	End of 3 months treatment in maintenance period

Collaborators and Investigators

• Sponsor: Ineos Healthcare Limited
• Investigators: Study Chair: Chief Medical Officer (Information at Ineos Healthcare Limited), Dr., INEOS Healthcare Limited

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (ANTICIPATED): September 1, 2011
• Study Completion (ANTICIPATED): October 1, 2011

Study Registration Dates

• First Submitted: February 13, 2009
• First Submitted That Met QC Criteria: February 13, 2009
• First Posted (ESTIMATE): February 16, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 19, 2010
• Last Update Submitted That Met QC Criteria: October 18, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: phosphate binder; Hyperphosphataemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Phosphorus Metabolism Disorders; Kidney Failure, Chronic; Renal Insufficiency; Hyperphosphatemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: ACT 402; 2008-004730-25 (EUDRACT_NUMBER)