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

Chronic Kidney Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00844662
• Other study ID #: ACT 402
• Secondary ID: 2008-004730-25
• Status: Terminated
• Phase: Phase 3
• First received: February 13, 2009
• Last updated: October 18, 2010
• Start date: July 2009
• Est. completion date: October 2011

Study information

• Verified date: October 2010
• Source: Ineos Healthcare Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCzech Republic: State Institute for Drug ControlSouth Africa: Medicines Control CouncilArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: National Health Surveillance AgencyItaly: The Italian Medicines AgencyBelgium: Federal Agency for Medicinal Products and Health ProductsBulgaria: Bulgarian Drug AgencyEstonia: The State Agency of MedicineHungary: National Institute of PharmacyLithuania: State Medicine Control Agency - Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySlovakia: State Institute for Drug ControlMexico: Ministry of HealthSerbia and Montenegro: Agency for Drugs and Medicinal Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1000
• Est. completion date: October 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Failure
• Hyperphosphatemia
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Fermagate
Film coated tablet 500mg
• Sevelamer hydrochloride
Tablet 800mg

Locations

Country	Name	City	State
Belgium	O.L.V Ziekenhuis	Aalst
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Brussel	Jette
Belgium	U. Z. Gasthuisberg	Leuven
Belgium	Hôpital de la Citadelle	Liège
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital Geral de Bonsucesso	Rio de Janeiro	RJ
Brazil	Nefroclinica de Uberlandia Ltda	Uberlandia	MG
Bulgaria	MHAT - Pazardzhik AD	Pazardzhik
Bulgaria	University Multiprofile Hospital for Active Treatment "Dr. G. Stransky"	Pleven
Bulgaria	MHAT - Plovdiv AD	Plovdiv
Bulgaria	MHAT - Rousse AD	Rousse
Bulgaria	MHAT 'Tokuda Hospital Sofia' AD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment and Emergency Medicine "Pirogov"	Sofia
Bulgaria	UMHAT 'Alexandrovska'	Sofia
Bulgaria	UMHAT 'Sv. Ivan Rilski' EAD	Sofia
Bulgaria	MHAT 'Sv. Anna - Varna' AD	Varna
Bulgaria	MHAT 'Sveta Marina'	Varna
Bulgaria	Centre of Haemodialysis and Nephrology MHAT 'Dr. Stefan Cherkezov' AD	Veliko Tarnovo
Czech Republic	Fakultní nemocnice u sv. Anny	Brno
Czech Republic	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	Nemocnice Znojmo	Znojmo
Estonia	North Estonia Regional Hospital	Tallinn
Estonia	West-Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Hungary	FMC Dialysis Centre	Budapest
Hungary	Diaverum Dialysis Centre	Hodmezovasarhely
Hungary	FMC Dializis Center Kecskemet	Kecskemet
Hungary	FMC Dializis Centrum Kft Vac Javorszky Odon Korhaz	Vác
Israel	Barzilai Medical Center	Ashkelon
Israel	Assaf Harofeh Medical Center	Beer Yaakov
Israel	Western Galilee Hospital - Nahariya	Naharia
Italy	Azienda Ospedaliera Istituti Ospitalieri di Cremona	Cremona	CR
Italy	Azienda Ospedaliera Policlinico di Modena	Modena	MO
Italy	Fondazione "S. Maugeri" IRCCS	Pavia	PV
Lithuania	B.Braun Avitum JSC	Kaunas
Lithuania	Diaverum klinikos JSC	Kaunas
Lithuania	Kaunas Medical University Hospital Public Institution	Kaunas
Lithuania	Diaverum klinikos JSC	Kedainiai
Lithuania	Diaverum klinikos JSC	Klaipeda
Lithuania	Siauliai Regional Hospital Public Institution	Siauliai
Lithuania	Diaverum klinikos JSC	Vilnius
Lithuania	Vilnius City University Hospital Public Institution	Vilnius
Mexico	Hospital y Clinica OCA SA de CV	Monterrey
Serbia	Clinical Center Zvezdara	Belgrade
Serbia	Clinical Center Nis	Nis
Serbia	Clinical Centre of Vojvodina	Novi Sad
Serbia	Clinical Center Zemun	Zemun
Slovakia	Logman a.s.	Banska Bystrica
Slovakia	Nephro s.r.o. Levice	Levice
Slovakia	Privat Nephro-Dialysis Centre Ldt Martin	Martin
Slovakia	LOGMAN a.s.	Trencin
South Africa	Grootte Schuur Hospital	Cape Town	Western Cape
South Africa	N1 City Hospital	Cape Town	Western Cape
South Africa	South Peninsula Dialysis	Cape Town	Western Cape
South Africa	Panorama Medi Clinic	Parow	Western Cape
South Africa	Tygerberg Hospital	Parow	Western Cape
United Kingdom	St Lukes Hospital	Bradford	Nthumb
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambs
United Kingdom	University Hospital of Wales	Cardiff	S Glam
United Kingdom	Leicester General Hospital	Leicester	Leics
United Kingdom	Royal Liverpool Hospital	Liverpool	Mersyd
United Kingdom	The Royal London Hospital	London	Gt Lon
United Kingdom	Norfolk and Norwich University Hospital	Norwich	Norflk
United Kingdom	Royal Berkshire Hospital	Reading
United Kingdom	Northern General Hospital	Sheffield
United States	CSRA Renal Services	Aiken	South Carolina
United States	Ramon Mendez MD PC (private practice)	Alexandria	Virginia
United States	Ramon Mendez, MD, PC (private practice)	Alexandria	Virginia
United States	South Arlington Dialysis Center	Arlington	Texas
United States	Cleveland William MD	Atlanta	Georgia
United States	National Institute of Clinical Research	Bakersfield	California
United States	Renal Associates of Baton Rouge	Baton Rouge	Louisiana
United States	Nassau Nephrology, LLP	Bellmore	New York
United States	Davita South Brunswick Dialysis Center	Brunswick	Georgia
United States	University of Vermont	Burlington	Vermont
United States	Bayview Nephrology	Erie	Pennsylvania
United States	North Shore University Health System	Evanston	Illinois
United States	Southwest Nephrology Associates	Evergreen Park	Illinois
United States	Clinical Research & Consulting Center LLC	Fairfax	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	U.S Renal Care	Grand Prairie	Texas
United States	U.S. Renal Care	Grand Prairie	Texas
United States	Arkansas Nephrology Services Ltd	Hot Springs	Arkansas
United States	Diagnostic Clinic of Houston	Houston	Texas
United States	SouthWest Houston Research LTD.	Houston	Texas
United States	Renal Medical Associates	Lynwood	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Academic Medical Research Institute Inc	Monterey Park	California
United States	Huq Cruz Strauss Masud PA	Neptune	New Jersey
United States	Discovery Medical Research Group Inc.	Ocala	Florida
United States	Pasadena Nephrology	Pasadena	California
United States	St. Joseph's Regional Medical Center	Paterson	New Jersey
United States	Renal Endocrine Associates PC	Pittsburgh	Pennsylvania
United States	Renal-Endocrine Associates	Pittsburgh	Pennsylvania
United States	Sierra View Nephrology SC	Porterville	California
United States	Renal Associates PA	San Antonio	Texas
United States	Western New England Transplant Associates	Springfield	Massachusetts
United States	Clinical Research Development Associates LLC	Springfield Gardens	New York
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Stanford Nephrology	Stamford	Connecticut
United States	Carolina Diabetes & Kidney Center	Sumter	South Carolina
United States	Carolina Diabetes and Kidney Center/ sumter Medical Specialist	Sumter	South Carolina
United States	Kidney Center Inc.	Thousand oaks	California
United States	Capitol Dialysis	Washington	District of Columbia
United States	Nephrology Associates, PA	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Ineos Healthcare Limited

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Bulgaria,  Czech Republic,  Estonia,  Hungary,  Israel,  Italy,  Lithuania,  Mexico,  Serbia,  Slovakia,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Control or not the level of serum phosphate		Within the treatment period	Yes
Secondary	Change from baseline in mean serum phosphate		End of 3 months treatment in maintenance period	Yes
Secondary	Change from baseline in calcium, calcium phosphate product and PTH level		End of 3 months treatment in maintenance period	Yes