Clinical trial NCT00841126: Phase III Study to Investigate the Safety and Efficacy of Fermagate and Lanthanum Carbonate
Official title: An Open, Randomized, Controlled, Parallel Group, Phase III Study to Investigate the Safety and Efficacy of Fermagate and Lanthanum Carbonate Together With a Randomized Placebo Controlled Double Blind Fermagate Comparison in Hemodialysis Patients With Hyperphosphatemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Kidney Failure
Keywords: Hyperphosphatemia
Phosphate binder
Lead sponsor: Ineos Healthcare Limited
Sponsor class: INDUSTRY
First posted: 2009-02-11
Enrollment: 657
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 hemodialysis, compared with a marketed phosphate binder, lanthanum carbonate and placebo.

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 1.78 mmol/L in patients who receive hemodialysis.

This is a 2-stage re-randomization design where Stage 1 is a randomized, open label comparison between fermagate and lanthanum carbonate (in a non-inferiority design) and Stage 2 is a randomized double blind comparison between fermagate and placebo (in a superiority design).

Objectives at Stage 1:

Primary Objective:

The primary objective is to establish the efficacy of fermagate by demonstrating the noninferiority (with possible assessment of superiority) of fermagate to lanthanum carbonate in lowering serum phosphate in hemodialysis patients.

Secondary objectives:

The secondary objectives are to:

1. Determine the safety of fermagate in hemodialysis patients.
2. Compare the effects of fermagate and lanthanum carbonate on measures of mineral metabolism, albumin, pre-albumin and iron status.

Objectives at Stage 2:

Stage 2 will use patients who complete the 3-month maintenance period of Stage 1 and who were originally randomized to fermagate.

Primary Objective:

The primary objective is to establish efficacy of fermagate by demonstrating the superiority of fermagate over placebo in lowering serum phosphate in hemodialysis patients.

Secondary objectives:

The secondary objectives are to:

1. Determine the safety of fermagate in hemodialysis patients.
2. Compare the effects of fermagate and placebo on measures of mineral metabolism, albumin, pre-albumin and iron status.

Eligibility criteria: Inclusion:

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 hemodialysis 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) Subjects (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 hyperphosphatemia.
6. Willing to abstain from taking any phosphate binder or oral magnesium-, oral aluminum- 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 randomization and inclusion into the treatment period, one of the following criteria must be fulfilled:
8. (a) Is not receiving phosphate binding medication at screen and has a screen serum phosphate value above 3.0 mmol/L (9.3 mg/dL)OR(b) Has a serum phosphate value of ≥1.94 mmol/L (≥6.0 mg/dL) at Washout Visit 2 to 4 or above 3.0 mmol/L (9.3 mg/dL) at visit 1 during washout.

Exclusion:

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 \>3.0 mg/dL (\>1.25 mmol/L).
7. A known history of hemochromatosis.
8. Subjects receiving either tetracycline or lithium treatment.
9. Subjects receiving nicotinamide (niacinamide) or niacin (nicotinic acid) alone (i.e. not as a constituent of a multivitamin supplementation).
10. A serum ferritin level of ≥1500 ng/mL (≥3370 pmol/L).
11. Non-elective hospitalization in the 4 weeks prior to screening.
12. Female subjects who are of childbearing potential and who are neither surgically sterilized nor using reliable contraceptive methods (hormonal, barrier methods or intrauterine device) or who are lactating or pregnant.
13. Current hypophosphatemia at screening (last 2 consecutive phosphate values of \<2.2 mg/dL \[\<0.7 mmol/L\]).
14. Known history of colorectal malignancy, familial polyposis coli and/or strong family history (in 2 or more first degree relatives) of these terms
15. A QTcF interval of \>560 ms at screen.
16. Known persistent (\>1 month) non compliance (\<70%) with prescribed medication regimens at screen.
17. Current clinically significant intestinal motility disorder.
18. Intestinal motility disorder with current or previous use of lanthanum carbonate.
19. Known intolerance to lanthanum carbonate or any excipients of fermagate or Fosrenol medication.
20. Subjects with inflammatory bowel disease that, in the investigator's opinion, is poorly controlled.
21. Subjects placed under guardianship or tutelage.
22. Subjects previously withdrawn from the study.

The above inclusion and exclusion criteria would be the same for all countries except the exclusion criteria of the QTc interval would be different for Germany (QTc interval of \>470ms at screen).

Primary outcomes:
measure: Stage 1: Control or not the level of serum phosphate
timeFrame: Within the treatment period
measure: Stage 2: Change from treated baseline in mean serum phosphate
timeFrame: At 4 weeks
Secondary outcomes:
measure: Stage 1: Change from baseline in mean serum phosphate
timeFrame: End of 3 months treatment in maintenance period
measure: Stage 1: Change from baseline in calcium, calcium phosphate product and PTH level
timeFrame: End of 3 months treatment in maintenance period
measure: Stage 2: Change from treated baseline in mean serum phosphate
timeFrame: At weeks 1, 2 and 3
measure: Stage 2: Change from treated baseline in Ca, Ca-phosphate product and PTH levels
timeFrame: At the end of weeks 1, 2, 3 and 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Nephrology Associates PC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Kidney Disease and Hypertension Center
state: Arizona
city: Tempe
country: United States
facility: Southwest Kidney Institute
state: Arizona
city: Jonesboro
country: United States
facility: US Renal Care
state: Arkansas
city: Pine Bluff
country: United States
facility: Wright Steven (Private Practice)
state: Arkansas
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Riverside
country: United States
facility: Apex Research of Riverside
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Simi Valley
country: United States
facility: Kidney Center Inc.
state: California
city: Tarzana
country: United States
facility: Nephrology Educational Services and Research
state: California
city: Whittier
country: United States
facility: American Institute of Research
state: California
city: Yoba City
country: United States
facility: North Valley Nephrology
state: California
city: Arvada
country: United States
facility: Western Nephrology & Metabolic Bone Disease PC
state: Colorado
city: Westminister
country: United States
facility: Western Nephrology & Metabolic Bone Disease PC
state: Colorado
city: Middlebury
country: United States
facility: Nephrology and Hypertension Associates
state: Connecticut
city: Coral Springs
country: United States
facility: South Florida Nephrology Group P.A.
state: Florida
city: Hudson
country: United States
facility: Outcomes Research International Inc.
state: Florida
city: Miami
country: United States
facility: Nephrology Associates of South Miami
state: Florida
city: Panama City
country: United States
facility: Nephrology Associates Research Center
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Macon
country: United States
facility: Renal Physicians of Georgia PC
state: Georgia
city: Meridian
country: United States
facility: Boise Kidney & Hypertension Institute
state: Idaho
city: Evergreen Park
country: United States
facility: Research by Design LLC
state: Illinois
city: Gurnee
country: United States
facility: North Suburban Nephrology
state: Illinois
city: Wichita
country: United States
facility: Kansas Nephrology Research Institute LLC
state: Kansas
city: Lafayette
country: United States
facility: Research Nurse Specialists LLC
state: Louisiana
city: Plymouth
country: United States
facility: Lazowski Piotr MD- PC
state: Massachusetts
city: Worcester
country: United States
facility: Fallon Clinic - Winthrop
state: Massachusetts
city: Berkley
country: United States
facility: William Beaumont Hospitals
state: Michigan
city: Detroit
country: United States
facility: St. Clair Specialty Physicians PC
state: Michigan
city: Columbus
country: United States
facility: Nephrology Associates P.C.
state: Mississippi
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Las Vagas
country: United States
facility: Kantor Nephrology Consultants Ltd.
state: Nevada
city: Brooklyn
country: United States
facility: Brookdale Physicians Dialysis Associates
state: New York
city: Buffalo
country: United States
facility: Hypertension and Renal Research Group
state: New York
city: New York
country: United States
facility: Lower Manhattan Dialysis Center
state: New York
city: Port Washington
country: United States
facility: Long Island Hypertension and Nephrology PLLC
state: New York
city: Raleigh
country: United States
facility: Wake Nephrology Associates PA
state: North Carolina
city: Cinncinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Youngstown
country: United States
facility: Humility of Mary Health Partners
state: Ohio
city: Lancaster
country: United States
facility: Hypertension and Kidney Specialists
state: Pennsylvania
city: Orangeburg
country: United States
facility: SC Nephrology & Hypertension Center Inc.
state: South Carolina
city: Chattanooga
country: United States
facility: Nephrology Associates
state: Tennessee
city: Nashville
country: United States
facility: Nephrology Associates
state: Tennessee
city: Arlington
country: United States
facility: U.S. Renal Care
state: Texas
city: Burleson
country: United States
facility: U.S. Renal Care
state: Texas
city: Fort Worth
country: United States
facility: U.S. Renal Care
state: Texas
city: Fort Worth
country: United States
facility: U.S. Renal Care
state: Texas
city: Greenville
country: United States
facility: Texas Renal Care
state: Texas
city: Houston
country: United States
facility: Ralph Plaza Nephrology
state: Texas
city: Irving
country: United States
facility: Dallas Nephrology Associates
state: Texas
city: Mansfield
country: United States
facility: US Renal Care
state: Texas
city: McAllen
country: United States
facility: U.S. Renal Care
state: Texas
city: San Antonio
country: United States
facility: Dukes Carl
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital and Clinic
state: Texas
city: Fairfax
country: United States
facility: Nephrology Associates of Northern Virginia
state: Virginia
city: Norfolk
country: United States
facility: Internal Medicine Kidney and Hypertension Center
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Virginia Beach
country: United States
facility: Tidewater Kidney Specialists
state: Virginia
city: Seattle
country: United States
facility: Northwest Kidney Center
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Pialba
country: Australia
facility: Hervey Bay Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Richmond
country: Australia
facility: Epworth Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Juiz de Fora
country: Brazil
facility: Hospital Universitario da Univ Federal de Juiz de Fora
state: MG
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Pedro Ernesto
state: RJ
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFESP
state: SP
city: Sorocaba
country: Brazil
facility: Faculdade de Ciencias Medicas de Sorocaba - Hosp Santa Lucin
state: SP
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Capital District Health Authority
state: Nova Scotia
city: Brampton
country: Canada
facility: William Osler Health Centre
state: Ontario
city: Kitchener
country: Canada
facility: Clinical Research Solutions Inc.
state: Ontario
city: London
country: Canada
facility: London Health Science Centre - University Campus Site
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Health Care Centre
state: Ontario
city: Gatineau
country: Canada
facility: Exsequi Recherche Clinique
state: Quebec
city: Greenfield Park
country: Canada
facility: Hospital Charles LeMoyne
state: Quebec
city: Montréal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Grenoble
country: France
facility: Clinique Mutualiste des Eaux Claires
state: 38
city: Amiens Cedex 1
country: France
facility: Centre Hospitalier Sud
state: 80
city: Aschaffenburg
country: Germany
facility: Gemeinschaftspraxis
state: BY
city: Coburg
country: Germany
facility: Klinikum Coburg
state: BY
city: Bad Koenig
country: Germany
facility: Prager Gerhard
state: HE
city: Hamburg
country: Germany
facility: Dialysezentrum Barmbek
state: HH
city: Hamburg
country: Germany
facility: Dialysepraxis Altona
state: HH
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
state: RP
city: B'Kara
country: Malta
facility: Mater Dei Hospital Medical Outpatient
city: B'Kara
country: Malta
facility: Mater Dei Hospital Renal Unit
city: Gozo
country: Malta
facility: Gozo General Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Dabrowa Gornicza
country: Poland
facility: Szpital Specjalistyczny
city: Golub Dobrzyn
country: Poland
facility: NZOZ Avitum-Stacja Dializ Sp.z.o.o
city: Rawicz
country: Poland
facility: NZOZ Miedzynarodowe Centrum Dializ Poznan Odz. Rawicz
city: Wroclaw
country: Poland
facility: Euromedic NZOZ Miedzynarodowe
city: Wroclaw
country: Poland
facility: NZOZ Miedzynarodowe Centrum Dializ
city: Bloemfontein
country: South Africa
facility: Netcare Private Hospital
state: Free State
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital
state: Gauteng
city: D'Urban
country: South Africa
facility: Entabeni Hospital
state: KZ-Natal
city: Durban
country: South Africa
facility: St. Augustines Hospital
state: KZ-Natal
city: Barcelona
country: Spain
facility: H Clinic i Provincial
city: Barcelona
country: Spain
facility: HU de Bellvitge
Study officials:
affiliation: INEOS Healthcare Ltd, UK
name: Information at Ineos Healthcare Limited (Chief Medical Officer)
role: STUDY_CHAIR
References: