Clinical trial NCT00844662: Phase III Study to Investigate the Safety and Efficacy of Fermagate and Sevelamer Hydrochloride
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Kidney Failure
Keywords: Hyperphosphataemia
phosphate binder
Lead sponsor: Ineos Healthcare Limited
Sponsor class: INDUSTRY
First posted: 2009-02-16
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Control or not the level of serum phosphate
timeFrame: Within the treatment period
Secondary outcomes:
measure: Change from baseline in mean serum phosphate
timeFrame: End of 3 months treatment in maintenance period
measure: Change from baseline in calcium, calcium phosphate product and PTH level
timeFrame: End of 3 months treatment in maintenance period
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Arkansas Nephrology Services Ltd
state: Arkansas
city: Bakersfield
country: United States
facility: National Institute of Clinical Research
state: California
city: Lynwood
country: United States
facility: Renal Medical Associates
state: California
city: Monterey Park
country: United States
facility: Academic Medical Research Institute Inc
state: California
city: Pasadena
country: United States
facility: Pasadena Nephrology
state: California
city: Porterville
country: United States
facility: Sierra View Nephrology SC
state: California
city: Thousand oaks
country: United States
facility: Kidney Center Inc.
state: California
city: Stamford
country: United States
facility: Stanford Nephrology
state: Connecticut
city: Washington
country: United States
facility: Capitol Dialysis
state: District of Columbia
city: Ocala
country: United States
facility: Discovery Medical Research Group Inc.
state: Florida
city: Atlanta
country: United States
facility: Cleveland William MD
state: Georgia
city: Brunswick
country: United States
facility: Davita South Brunswick Dialysis Center
state: Georgia
city: Evanston
country: United States
facility: North Shore University Health System
state: Illinois
city: Evergreen Park
country: United States
facility: Southwest Nephrology Associates
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Baton Rouge
country: United States
facility: Renal Associates of Baton Rouge
state: Louisiana
city: Springfield
country: United States
facility: Western New England Transplant Associates
state: Massachusetts
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Neptune
country: United States
facility: Huq Cruz Strauss Masud PA
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Regional Medical Center
state: New Jersey
city: Bellmore
country: United States
facility: Nassau Nephrology, LLP
state: New York
city: Springfield Gardens
country: United States
facility: Clinical Research Development Associates LLC
state: New York
city: Winston-Salem
country: United States
facility: Nephrology Associates, PA
state: North Carolina
city: Erie
country: United States
facility: Bayview Nephrology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Renal Endocrine Associates PC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Renal-Endocrine Associates
state: Pennsylvania
city: Aiken
country: United States
facility: CSRA Renal Services
state: South Carolina
city: Sumter
country: United States
facility: Carolina Diabetes & Kidney Center
state: South Carolina
city: Sumter
country: United States
facility: Carolina Diabetes and Kidney Center/ sumter Medical Specialist
state: South Carolina
city: Arlington
country: United States
facility: South Arlington Dialysis Center
state: Texas
city: Grand Prairie
country: United States
facility: U.S Renal Care
state: Texas
city: Grand Prairie
country: United States
facility: U.S. Renal Care
state: Texas
city: Houston
country: United States
facility: Diagnostic Clinic of Houston
state: Texas
city: Houston
country: United States
facility: SouthWest Houston Research LTD.
state: Texas
city: San Antonio
country: United States
facility: Renal Associates PA
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Alexandria
country: United States
facility: Ramon Mendez MD PC (private practice)
state: Virginia
city: Alexandria
country: United States
facility: Ramon Mendez, MD, PC (private practice)
state: Virginia
city: Fairfax
country: United States
facility: Clinical Research & Consulting Center LLC
state: Virginia
city: Aalst
country: Belgium
facility: O.L.V Ziekenhuis
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Leuven
country: Belgium
facility: U. Z. Gasthuisberg
city: Liège
country: Belgium
facility: Hôpital de la Citadelle
city: Uberlandia
country: Brazil
facility: Nefroclinica de Uberlandia Ltda
state: MG
city: Rio de Janeiro
country: Brazil
facility: Hospital Geral de Bonsucesso
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Pazardzhik
country: Bulgaria
facility: MHAT - Pazardzhik AD
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Dr. G. Stransky"
city: Plovdiv
country: Bulgaria
facility: MHAT - Plovdiv AD
city: Rousse
country: Bulgaria
facility: MHAT - Rousse AD
city: Sofia
country: Bulgaria
facility: MHAT 'Tokuda Hospital Sofia' AD
city: Sofia
country: Bulgaria
facility: UMHAT 'Alexandrovska'
city: Sofia
country: Bulgaria
facility: UMHAT 'Sv. Ivan Rilski' EAD
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment and Emergency Medicine "Pirogov"
city: Varna
country: Bulgaria
facility: MHAT 'Sv. Anna - Varna' AD
city: Varna
country: Bulgaria
facility: MHAT 'Sveta Marina'
city: Veliko Tarnovo
country: Bulgaria
facility: Centre of Haemodialysis and Nephrology MHAT 'Dr. Stefan Cherkezov' AD
city: Brno
country: Czech Republic
facility: Fakultní nemocnice u sv. Anny
city: Liberec
country: Czech Republic
facility: Krajska nemocnice Liberec, a.s.
city: Prachatice
country: Czech Republic
facility: Nemocnice v Prachaticich, a.s.
city: Praha 6
country: Czech Republic
facility: VFN Praha
city: Tabor
country: Czech Republic
facility: Nemocnice Tabor a.s.
city: Znojmo
country: Czech Republic
facility: Nemocnice Znojmo
city: Tallinn
country: Estonia
facility: West-Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: North Estonia Regional Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Budapest
country: Hungary
facility: FMC Dialysis Centre
city: Hodmezovasarhely
country: Hungary
facility: Diaverum Dialysis Centre
city: Kecskemet
country: Hungary
facility: FMC Dializis Center Kecskemet
city: Vác
country: Hungary
facility: FMC Dializis Centrum Kft Vac Javorszky Odon Korhaz
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Yaakov
country: Israel
facility: Assaf Harofeh Medical Center
city: Naharia
country: Israel
facility: Western Galilee Hospital - Nahariya
city: Cremona
country: Italy
facility: Azienda Ospedaliera Istituti Ospitalieri di Cremona
state: CR
city: Modena
country: Italy
facility: Azienda Ospedaliera Policlinico di Modena
state: MO
city: Pavia
country: Italy
facility: Fondazione "S. Maugeri" IRCCS
state: PV
city: Kaunas
country: Lithuania
facility: Diaverum klinikos JSC
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital Public Institution
city: Kaunas
country: Lithuania
facility: B.Braun Avitum JSC
city: Kedainiai
country: Lithuania
facility: Diaverum klinikos JSC
city: Klaipeda
country: Lithuania
facility: Diaverum klinikos JSC
city: Siauliai
country: Lithuania
facility: Siauliai Regional Hospital Public Institution
city: Vilnius
country: Lithuania
facility: Diaverum klinikos JSC
city: Vilnius
country: Lithuania
facility: Vilnius City University Hospital Public Institution
city: Monterrey
country: Mexico
facility: Hospital y Clinica OCA SA de CV
city: Belgrade
country: Serbia
facility: Clinical Center Zvezdara
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Zemun
country: Serbia
facility: Clinical Center Zemun
city: Banska Bystrica
country: Slovakia
facility: Logman a.s.
city: Levice
country: Slovakia
facility: Nephro s.r.o. Levice
city: Martin
country: Slovakia
facility: Privat Nephro-Dialysis Centre Ldt Martin
city: Trencin
country: Slovakia
facility: LOGMAN a.s.
city: Cape Town
country: South Africa
facility: N1 City Hospital
state: Western Cape
city: Cape Town
country: South Africa
facility: South Peninsula Dialysis
state: Western Cape
city: Cape Town
country: South Africa
facility: Grootte Schuur Hospital
state: Western Cape
city: Parow
country: South Africa
facility: Panorama Medi Clinic
state: Western Cape
city: Parow
country: South Africa
facility: Tygerberg Hospital
state: Western Cape
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambs
city: London
country: United Kingdom
facility: The Royal London Hospital
state: Gt Lon
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: Leics
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospital
state: Mersyd
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: Norflk
city: Bradford
country: United Kingdom
facility: St Lukes Hospital
state: Nthumb
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: S Glam
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
Study officials:
affiliation: Ineos Healthcare Limited
name: Chief Medical Officer (Information at Ineos Healthcare Limited), Dr.
role: STUDY_CHAIR
References: