Phase III Study to Investigate the Safety and Efficacy of Fermagate and Lanthanum Carbonate

NCT ID: NCT00841126

Last Updated: 2010-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

657 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2011-07-31

Brief Summary

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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

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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.

Conditions

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Chronic Kidney Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Magnesium iron hydroxycarbonate

Group Type EXPERIMENTAL

Magnesium iron hydroxycarbonate

Intervention Type DRUG

500 mg tablets, administered orally: initial dosage 500 or 1000 mg (total daily dose 1500 or 3000 mg) depending on serum phosphate concentration, titrated to a maximum DAILY dose of 9000 mg). The total daily dose should be divided and taken with meals. Any SINGLE dose should not exceed 3000 mg.

Lanthanum carbonate

Group Type ACTIVE_COMPARATOR

Lanthanum carbonate

Intervention Type DRUG

750 mg chewable tablets, administered orally: initial dosage 750 mg up to 3-times daily (total daily dose 2250 mg), titrated to a maximum SINGLE dose of 1500 mg (DAILY dose 3750 mg). The total daily dose should be divided and taken with meals.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

0 mg (500 mg-size) tablets, administered orally: The total daily dose should be divided and taken with meals. Any SINGLE dose should not exceed 6 tablets.

Interventions

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Magnesium iron hydroxycarbonate

500 mg tablets, administered orally: initial dosage 500 or 1000 mg (total daily dose 1500 or 3000 mg) depending on serum phosphate concentration, titrated to a maximum DAILY dose of 9000 mg). The total daily dose should be divided and taken with meals. Any SINGLE dose should not exceed 3000 mg.

Intervention Type DRUG

Lanthanum carbonate

750 mg chewable tablets, administered orally: initial dosage 750 mg up to 3-times daily (total daily dose 2250 mg), titrated to a maximum SINGLE dose of 1500 mg (DAILY dose 3750 mg). The total daily dose should be divided and taken with meals.

Intervention Type DRUG

Placebo

0 mg (500 mg-size) tablets, administered orally: The total daily dose should be divided and taken with meals. Any SINGLE dose should not exceed 6 tablets.

Intervention Type DRUG

Other Intervention Names

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Alpharen, magnesium iron hydroxycarbonate Fosrenol

Eligibility Criteria

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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 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ineos Healthcare Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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INEOS Healthcare Limited

Principal Investigators

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Information at Ineos Healthcare Limited (Chief Medical Officer)

Role: STUDY_CHAIR

INEOS Healthcare Ltd, UK

Locations

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Nephrology Associates PC

Birmingham, Alabama, United States

Site Status

Arizona Kidney Disease and Hypertension Center

Phoenix, Arizona, United States

Site Status

Southwest Kidney Institute

Tempe, Arizona, United States

Site Status

US Renal Care

Jonesboro, Arkansas, United States

Site Status

Wright Steven (Private Practice)

Pine Bluff, Arkansas, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Apex Research of Riverside

Riverside, California, United States

Site Status

North America Research Institute

San Dimas, California, United States

Site Status

Kidney Center Inc.

Simi Valley, California, United States

Site Status

Nephrology Educational Services and Research

Tarzana, California, United States

Site Status

American Institute of Research

Whittier, California, United States

Site Status

North Valley Nephrology

Yoba City, California, United States

Site Status

Western Nephrology & Metabolic Bone Disease PC

Arvada, Colorado, United States

Site Status

Western Nephrology & Metabolic Bone Disease PC

Westminister, Colorado, United States

Site Status

Nephrology and Hypertension Associates

Middlebury, Connecticut, United States

Site Status

South Florida Nephrology Group P.A.

Coral Springs, Florida, United States

Site Status

Outcomes Research International Inc.

Hudson, Florida, United States

Site Status

Nephrology Associates of South Miami

Miami, Florida, United States

Site Status

Nephrology Associates Research Center

Panama City, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Renal Physicians of Georgia PC

Macon, Georgia, United States

Site Status

Boise Kidney & Hypertension Institute

Meridian, Idaho, United States

Site Status

Research by Design LLC

Evergreen Park, Illinois, United States

Site Status

North Suburban Nephrology

Gurnee, Illinois, United States

Site Status

Kansas Nephrology Research Institute LLC

Wichita, Kansas, United States

Site Status

Research Nurse Specialists LLC

Lafayette, Louisiana, United States

Site Status

Lazowski Piotr MD- PC

Plymouth, Massachusetts, United States

Site Status

Fallon Clinic - Winthrop

Worcester, Massachusetts, United States

Site Status

William Beaumont Hospitals

Berkley, Michigan, United States

Site Status

St. Clair Specialty Physicians PC

Detroit, Michigan, United States

Site Status

Nephrology Associates P.C.

Columbus, Mississippi, United States

Site Status

Creighton University

Omaha, Nebraska, United States

Site Status

Kantor Nephrology Consultants Ltd.

Las Vagas, Nevada, United States

Site Status

Brookdale Physicians Dialysis Associates

Brooklyn, New York, United States

Site Status

Hypertension and Renal Research Group

Buffalo, New York, United States

Site Status

Lower Manhattan Dialysis Center

New York, New York, United States

Site Status

Long Island Hypertension and Nephrology PLLC

Port Washington, New York, United States

Site Status

Wake Nephrology Associates PA

Raleigh, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cinncinnati, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Humility of Mary Health Partners

Youngstown, Ohio, United States

Site Status

Hypertension and Kidney Specialists

Lancaster, Pennsylvania, United States

Site Status

SC Nephrology & Hypertension Center Inc.

Orangeburg, South Carolina, United States

Site Status

Nephrology Associates

Chattanooga, Tennessee, United States

Site Status

Nephrology Associates

Nashville, Tennessee, United States

Site Status

U.S. Renal Care

Arlington, Texas, United States

Site Status

U.S. Renal Care

Burleson, Texas, United States

Site Status

U.S. Renal Care

Fort Worth, Texas, United States

Site Status

U.S. Renal Care

Fort Worth, Texas, United States

Site Status

Texas Renal Care

Greenville, Texas, United States

Site Status

Ralph Plaza Nephrology

Houston, Texas, United States

Site Status

Dallas Nephrology Associates

Irving, Texas, United States

Site Status

US Renal Care

Mansfield, Texas, United States

Site Status

U.S. Renal Care

McAllen, Texas, United States

Site Status

Dukes Carl

San Antonio, Texas, United States

Site Status

San Antonio Kidney Disease Center

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Scott and White Memorial Hospital and Clinic

Temple, Texas, United States

Site Status

Nephrology Associates of Northern Virginia

Fairfax, Virginia, United States

Site Status

Internal Medicine Kidney and Hypertension Center

Norfolk, Virginia, United States

Site Status

Clinical Research Associates of Tidewater

Norfolk, Virginia, United States

Site Status

Tidewater Kidney Specialists

Virginia Beach, Virginia, United States

Site Status

Northwest Kidney Center

Seattle, Washington, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Hervey Bay Hospital

Pialba, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Launceston General Hospital

Launceston, Tasmania, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Epworth Hospital

Richmond, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Hospital Universitario da Univ Federal de Juiz de Fora

Juiz de Fora, Minas Gerais, Brazil

Site Status

Hospital Universitario Pedro Ernesto

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Universidade Federal de Sao Paulo - UNIFESP

São Paulo, São Paulo, Brazil

Site Status

Faculdade de Ciencias Medicas de Sorocaba - Hosp Santa Lucin

Sorocaba, São Paulo, Brazil

Site Status

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status

Capital District Health Authority

Halifax, Nova Scotia, Canada

Site Status

William Osler Health Centre

Brampton, Ontario, Canada

Site Status

Clinical Research Solutions Inc.

Kitchener, Ontario, Canada

Site Status

London Health Science Centre - University Campus Site

London, Ontario, Canada

Site Status

St. Michael's Health Care Centre

Toronto, Ontario, Canada

Site Status

Exsequi Recherche Clinique

Gatineau, Quebec, Canada

Site Status

Hospital Charles LeMoyne

Greenfield Park, Quebec, Canada

Site Status

Royal Victoria Hospital

Montreal, Quebec, Canada

Site Status

Clinique Mutualiste des Eaux Claires

Grenoble, 38, France

Site Status

Centre Hospitalier Sud

Amiens, 80, France

Site Status

Gemeinschaftspraxis

Aschaffenburg, Bavaria, Germany

Site Status

Klinikum Coburg

Coburg, Bavaria, Germany

Site Status

Dialysezentrum Barmbek

Hamburg, City state of Hamburg, Germany

Site Status

Dialysepraxis Altona

Hamburg, City state of Hamburg, Germany

Site Status

Prager Gerhard

Bad König, Hesse, Germany

Site Status

Westpfalz-Klinikum GmbH

Kaiserslautern, Rhineland-Palatinate, Germany

Site Status

Mater Dei Hospital Medical Outpatient

Birkirkara, , Malta

Site Status

Mater Dei Hospital Renal Unit

Birkirkara, , Malta

Site Status

Gozo General Hospital

Gozo, , Malta

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

Middlemore Hospital

Auckland, , New Zealand

Site Status

Wellington Hospital

Wellington, , New Zealand

Site Status

Szpital Specjalistyczny

Dąbrowa Górnicza, , Poland

Site Status

NZOZ Avitum-Stacja Dializ Sp.z.o.o

Golub-Dobrzyń, , Poland

Site Status

NZOZ Miedzynarodowe Centrum Dializ Poznan Odz. Rawicz

Rawicz, , Poland

Site Status

Euromedic NZOZ Miedzynarodowe

Wroclaw, , Poland

Site Status

NZOZ Miedzynarodowe Centrum Dializ

Wroclaw, , Poland

Site Status

Netcare Private Hospital

Bloemfontein, Free State, South Africa

Site Status

Chris Hani Baragwanath Hospital

Johannesburg, Gauteng, South Africa

Site Status

St. Augustines Hospital

Durban, KZ-Natal, South Africa

Site Status

Entabeni Hospital

Durbanville, KZ-Natal, South Africa

Site Status

H Clinic i Provincial

Barcelona, , Spain

Site Status

HU de Bellvitge

Barcelona, , Spain

Site Status

Countries

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United States Australia Brazil Canada France Germany Malta New Zealand Poland South Africa Spain

Other Identifiers

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2008-004729-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACT 401

Identifier Type: -

Identifier Source: org_study_id