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

Phase 3

Terminated

• Conditions: Chronic Kidney Failure
• Interventions: Drug: Sevelamer hydrochloride; Drug: Fermagate

• Registration Number: NCT00844662
• Lead Sponsor: Ineos Healthcare Limited

Brief Summary

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.

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 Timeline

• Study First Submitted: 2009-02-13
• Study First Submitted QC: 2009-02-13
• Study First Posted: 2009-02-16
• Study Start: 2009-07
• Status Verified: 2010-10
• Last Update Submitted: 2010-10-18
• Last Update Posted: 2010-10-19
• Primary Completion: 2011-09
• Study Completion: 2011-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1000

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Sevelamer hydrochloride	-
1	Fermagate	-

Primary Outcome Measures

Name	Time	Method
Control or not the level of serum phosphate	Within the treatment period

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (106)

Cleveland William MD; 🇺🇸 Atlanta, Georgia, United States

Diagnostic Clinic of Houston; 🇺🇸 Houston, Texas, United States

SouthWest Houston Research LTD.; 🇺🇸 Houston, Texas, United States

Renal Associates PA; 🇺🇸 San Antonio, Texas, United States

Huq Cruz Strauss Masud PA; 🇺🇸 Neptune, New Jersey, United States

Hurley Medical Center; 🇺🇸 Flint, Michigan, United States

Davita South Brunswick Dialysis Center; 🇺🇸 Brunswick, Georgia, United States

Western New England Transplant Associates; 🇺🇸 Springfield, Massachusetts, United States

St. Joseph's Regional Medical Center; 🇺🇸 Paterson, New Jersey, United States

Clinical Research Development Associates LLC; 🇺🇸 Springfield Gardens, New York, United States

Ramon Mendez MD PC (private practice); 🇺🇸 Alexandria, Virginia, United States

U.S. Renal Care; 🇺🇸 Grand Prairie, Texas, United States

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States

Nassau Nephrology, LLP; 🇺🇸 Bellmore, New York, United States

Southwest Nephrology Associates; 🇺🇸 Evergreen Park, Illinois, United States

Clinical Center Nis; 🇷🇸 Nis, Serbia

Renal Associates of Baton Rouge; 🇺🇸 Baton Rouge, Louisiana, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

Nephrology Associates, PA; 🇺🇸 Winston-Salem, North Carolina, United States

MHAT 'Sv. Anna - Varna' AD; 🇧🇬 Varna, Bulgaria

MHAT 'Sveta Marina'; 🇧🇬 Varna, Bulgaria

Pasadena Nephrology; 🇺🇸 Pasadena, California, United States

Kidney Center Inc.; 🇺🇸 Thousand oaks, California, United States

Sierra View Nephrology SC; 🇺🇸 Porterville, California, United States

National Institute of Clinical Research; 🇺🇸 Bakersfield, California, United States

Renal Medical Associates; 🇺🇸 Lynwood, California, United States

Academic Medical Research Institute Inc; 🇺🇸 Monterey Park, California, United States

Stanford Nephrology; 🇺🇸 Stamford, Connecticut, United States

Discovery Medical Research Group Inc.; 🇺🇸 Ocala, Florida, United States

North Shore University Health System; 🇺🇸 Evanston, Illinois, United States

Renal Endocrine Associates PC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Carolina Diabetes & Kidney Center; 🇺🇸 Sumter, South Carolina, United States

Renal-Endocrine Associates; 🇺🇸 Pittsburgh, Pennsylvania, United States

CSRA Renal Services; 🇺🇸 Aiken, South Carolina, United States

Bayview Nephrology; 🇺🇸 Erie, Pennsylvania, United States

U.S Renal Care; 🇺🇸 Grand Prairie, Texas, United States

South Arlington Dialysis Center; 🇺🇸 Arlington, Texas, United States

Clinical Research & Consulting Center LLC; 🇺🇸 Fairfax, Virginia, United States

Ramon Mendez, MD, PC (private practice); 🇺🇸 Alexandria, Virginia, United States

Universitair Ziekenhuis Brussel; 🇧🇪 Jette, Belgium

O.L.V Ziekenhuis; 🇧🇪 Aalst, Belgium

University of Vermont; 🇺🇸 Burlington, Vermont, United States

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

U. Z. Gasthuisberg; 🇧🇪 Leuven, Belgium

Hôpital de la Citadelle; 🇧🇪 Liège, Belgium

Hospital Geral de Bonsucesso; 🇧🇷 Rio de Janeiro, RJ, Brazil

MHAT - Pazardzhik AD; 🇧🇬 Pazardzhik, Bulgaria

Nefroclinica de Uberlandia Ltda; 🇧🇷 Uberlandia, MG, Brazil

MHAT - Plovdiv AD; 🇧🇬 Plovdiv, Bulgaria

University Multiprofile Hospital for Active Treatment "Dr. G. Stransky"; 🇧🇬 Pleven, Bulgaria

Fakultní nemocnice u sv. Anny; 🇨🇿 Brno, Czech Republic

Centre of Haemodialysis and Nephrology MHAT 'Dr. Stefan Cherkezov' AD; 🇧🇬 Veliko Tarnovo, Bulgaria

Hospital Sao Lucas - PUCRS; 🇧🇷 Porto Alegre, RS, Brazil

MHAT - Rousse AD; 🇧🇬 Rousse, Bulgaria

Multiprofile Hospital for Active Treatment and Emergency Medicine "Pirogov"; 🇧🇬 Sofia, Bulgaria

MHAT 'Tokuda Hospital Sofia' AD; 🇧🇬 Sofia, Bulgaria

UMHAT 'Alexandrovska'; 🇧🇬 Sofia, Bulgaria

UMHAT 'Sv. Ivan Rilski' EAD; 🇧🇬 Sofia, Bulgaria

Krajska nemocnice Liberec, a.s.; 🇨🇿 Liberec, Czech Republic

Nemocnice v Prachaticich, a.s.; 🇨🇿 Prachatice, Czech Republic

VFN Praha; 🇨🇿 Praha 6, Czech Republic

Nemocnice Tabor a.s.; 🇨🇿 Tabor, Czech Republic

Tartu University Hospital; 🇪🇪 Tartu, Estonia

Diaverum Dialysis Centre; 🇭🇺 Hodmezovasarhely, Hungary

FMC Dialysis Centre; 🇭🇺 Budapest, Hungary

Barzilai Medical Center; 🇮🇱 Ashkelon, Israel

Western Galilee Hospital - Nahariya; 🇮🇱 Naharia, Israel

Azienda Ospedaliera Policlinico di Modena; 🇮🇹 Modena, MO, Italy

Fondazione "S. Maugeri" IRCCS; 🇮🇹 Pavia, PV, Italy

Azienda Ospedaliera Istituti Ospitalieri di Cremona; 🇮🇹 Cremona, CR, Italy

Diaverum klinikos JSC; 🇱🇹 Vilnius, Lithuania

Siauliai Regional Hospital Public Institution; 🇱🇹 Siauliai, Lithuania

Vilnius City University Hospital Public Institution; 🇱🇹 Vilnius, Lithuania

B.Braun Avitum JSC; 🇱🇹 Kaunas, Lithuania

Hospital y Clinica OCA SA de CV; 🇲🇽 Monterrey, Mexico

Clinical Center Zvezdara; 🇷🇸 Belgrade, Serbia

Clinical Center Zemun; 🇷🇸 Zemun, Serbia

Clinical Centre of Vojvodina; 🇷🇸 Novi Sad, Serbia

Nephro s.r.o. Levice; 🇸🇰 Levice, Slovakia

LOGMAN a.s.; 🇸🇰 Trencin, Slovakia

Logman a.s.; 🇸🇰 Banska Bystrica, Slovakia

Privat Nephro-Dialysis Centre Ldt Martin; 🇸🇰 Martin, Slovakia

N1 City Hospital; 🇿🇦 Cape Town, Western Cape, South Africa

South Peninsula Dialysis; 🇿🇦 Cape Town, Western Cape, South Africa

Addenbrooke's Hospital; 🇬🇧 Cambridge, Cambs, United Kingdom

The Royal London Hospital; 🇬🇧 London, Gt Lon, United Kingdom

Royal Liverpool Hospital; 🇬🇧 Liverpool, Mersyd, United Kingdom

Norfolk and Norwich University Hospital; 🇬🇧 Norwich, Norflk, United Kingdom

University Hospital of Wales; 🇬🇧 Cardiff, S Glam, United Kingdom

Leicester General Hospital; 🇬🇧 Leicester, Leics, United Kingdom

Royal Berkshire Hospital; 🇬🇧 Reading, United Kingdom

St Lukes Hospital; 🇬🇧 Bradford, Nthumb, United Kingdom

Northern General Hospital; 🇬🇧 Sheffield, United Kingdom

Grootte Schuur Hospital; 🇿🇦 Cape Town, Western Cape, South Africa

Nemocnice Znojmo; 🇨🇿 Znojmo, Czech Republic

North Estonia Regional Hospital; 🇪🇪 Tallinn, Estonia

FMC Dializis Center Kecskemet; 🇭🇺 Kecskemet, Hungary

West-Tallinn Central Hospital; 🇪🇪 Tallinn, Estonia

FMC Dializis Centrum Kft Vac Javorszky Odon Korhaz; 🇭🇺 Vác, Hungary

Assaf Harofeh Medical Center; 🇮🇱 Beer Yaakov, Israel

Kaunas Medical University Hospital Public Institution; 🇱🇹 Kaunas, Lithuania

Tygerberg Hospital; 🇿🇦 Parow, Western Cape, South Africa

Panorama Medi Clinic; 🇿🇦 Parow, Western Cape, South Africa

Arkansas Nephrology Services Ltd; 🇺🇸 Hot Springs, Arkansas, United States

Capitol Dialysis; 🇺🇸 Washington, District of Columbia, United States

Carolina Diabetes and Kidney Center/ sumter Medical Specialist; 🇺🇸 Sumter, South Carolina, United States