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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Failure
• Intervention / Treatment: Drug: Magnesium iron hydroxycarbonate; Drug: Lanthanum carbonate; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 657
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Wollongong, New South Wales, Australia, 2500
      • Wollongong Hospital
  • Queensland
    • Pialba, Queensland, Australia, 4655
      • Hervey Bay Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Tasmania
    • Launceston, Tasmania, Australia, 7250
      • Launceston General Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3065
      • Royal Melbourne Hospital
    • Richmond, Victoria, Australia, 3121
      • Epworth Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• Brazil
  • MG
    • Juiz de Fora, MG, Brazil, 36038-330
      • Hospital Universitario da Univ Federal de Juiz de Fora
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20551-030
      • Hospital Universitário Pedro Ernesto
  • SP
    • Sao Paulo, SP, Brazil, 04023-900
      • Universidade Federal de São Paulo - UNIFESP
    • Sorocaba, SP, Brazil, 18030-083
      • Faculdade de Ciencias Medicas de Sorocaba - Hosp Santa Lucin
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Capital District Health Authority
  • Ontario
    • Brampton, Ontario, Canada, L6W 2Z8
      • William Osler Health Centre
    • Kitchener, Ontario, Canada, N2H 5Z8
      • Clinical Research Solutions Inc.
    • London, Ontario, Canada, N6A 5A5
      • London Health Science Centre - University Campus Site
    • Toronto, Ontario, Canada, M5C 2T2
      • St. Michael's Health Care Centre
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 4B7
      • Exsequi Recherche Clinique
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hospital Charles Lemoyne
    • Montréal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
• France
  • 38
    • Grenoble, 38, France, 38028
      • Clinique Mutualiste des Eaux Claires
  • 80
    • Amiens Cedex 1, 80, France, 80054
      • Centre Hospitalier Sud
• Germany
  • BY
    • Aschaffenburg, BY, Germany, 63741
      • Gemeinschaftspraxis
    • Coburg, BY, Germany, 96450
      • Klinikum Coburg
  • HE
    • Bad Koenig, HE, Germany, 64732
      • Prager Gerhard
  • HH
    • Hamburg, HH, Germany, 22297
      • Dialysezentrum Barmbek
    • Hamburg, HH, Germany, 22767
      • Dialysepraxis Altona
  • RP
    • Kaiserslautern, RP, Germany, 67655
      • Westpfalz-Klinikum GmbH
• Malta
  • B'Kara, Malta, MSD2090
    • Mater Dei Hospital Medical Outpatient
  • B'Kara, Malta, MSD2090
    • Mater Dei Hospital Renal Unit
  • Gozo, Malta
    • Gozo General Hospital
• New Zealand
  • Auckland, New Zealand, 1640
    • Middlemore Hospital
  • Auckland, New Zealand, 1010
    • Auckland City Hospital
  • Wellington, New Zealand, 6002
    • Wellington Hospital
• Poland
  • Dabrowa Gornicza, Poland, 41-300
    • Szpital Specjalistyczny
  • Golub Dobrzyn, Poland
    • NZOZ Avitum-Stacja Dializ Sp.z.o.o
  • Rawicz, Poland, 63-900
    • NZOZ Miedzynarodowe Centrum Dializ Poznan Odz. Rawicz
  • Wroclaw, Poland, 51-149
    • Euromedic NZOZ Miedzynarodowe
  • Wroclaw, Poland, 52-223
    • NZOZ Miedzynarodowe Centrum Dializ
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Netcare Private Hospital
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1
      • Chris Hani Baragwanath Hospital
  • KZ-Natal
    • D'Urban, KZ-Natal, South Africa, 4001
      • Entabeni Hospital
    • Durban, KZ-Natal, South Africa, 4001
      • St. Augustines Hospital
• Spain
  • Barcelona, Spain, 8036
    • H Clinic i Provincial
  • Barcelona, Spain, 8907
    • HU de Bellvitge
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Nephrology Associates PC
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Kidney Disease and Hypertension Center
    • Tempe, Arizona, United States, 85284
      • Southwest Kidney Institute
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • US Renal Care
    • Pine Bluff, Arkansas, United States, 71603
      • Wright Steven (Private Practice)
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Riverside, California, United States, 92505
      • Apex Research of Riverside
    • San Dimas, California, United States, 91773
      • North America Research Institute
    • Simi Valley, California, United States, 93065
      • Kidney Center Inc.
    • Tarzana, California, United States, 91356
      • Nephrology Educational Services and Research
    • Whittier, California, United States, 90603
      • American Institute of Research
    • Yoba City, California, United States, 95991
      • North Valley Nephrology
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Western Nephrology & Metabolic Bone Disease PC
    • Westminister, Colorado, United States, 80031
      • Western Nephrology & Metabolic Bone Disease PC
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Nephrology and Hypertension Associates
  • Florida
    • Coral Springs, Florida, United States, 33071
      • South Florida Nephrology Group P.A.
    • Hudson, Florida, United States, 34667
      • Outcomes Research International Inc.
    • Miami, Florida, United States, 33173
      • Nephrology Associates of South Miami
    • Panama City, Florida, United States, 32401
      • Nephrology Associates Research Center
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Macon, Georgia, United States, 31217
      • Renal Physicians of Georgia PC
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney & Hypertension Institute
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Research by Design LLC
    • Gurnee, Illinois, United States, 60031
      • North Suburban Nephrology
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Kansas Nephrology Research Institute LLC
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Research Nurse Specialists LLC
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Lazowski Piotr MD- PC
    • Worcester, Massachusetts, United States, 01608
      • Fallon Clinic - Winthrop
  • Michigan
    • Berkley, Michigan, United States, 48073
      • William Beaumont Hospitals
    • Detroit, Michigan, United States, 48236
      • St. Clair Specialty Physicians PC
  • Mississippi
    • Columbus, Mississippi, United States, 39705
      • Nephrology Associates P.C.
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University
  • Nevada
    • Las Vagas, Nevada, United States, 89169
      • Kantor Nephrology Consultants Ltd.
  • New York
    • Brooklyn, New York, United States, 11219
      • Brookdale Physicians Dialysis Associates
    • Buffalo, New York, United States, 14209
      • Hypertension and Renal Research Group
    • New York, New York, United States, 10016
      • Lower Manhattan Dialysis Center
    • Port Washington, New York, United States, 11050
      • Long Island Hypertension and Nephrology PLLC
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Wake Nephrology Associates PA
  • Ohio
    • Cinncinnati, Ohio, United States, 45206
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Youngstown, Ohio, United States, 44501
      • Humility of Mary Health Partners
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Hypertension and Kidney Specialists
  • South Carolina
    • Orangeburg, South Carolina, United States, 29115
      • SC Nephrology & Hypertension Center Inc.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Nephrology Associates
    • Nashville, Tennessee, United States, 37205
      • Nephrology Associates
  • Texas
    • Arlington, Texas, United States, 76011
      • U.S. Renal Care
    • Burleson, Texas, United States, 76028
      • U.S. Renal Care
    • Fort Worth, Texas, United States, 76105
      • U.S. Renal Care
    • Fort Worth, Texas, United States, 76106
      • U.S. Renal Care
    • Greenville, Texas, United States, 75402
      • Texas Renal Care
    • Houston, Texas, United States, 77004
      • Ralph Plaza Nephrology
    • Irving, Texas, United States, 75061
      • Dallas Nephrology Associates
    • Mansfield, Texas, United States, 76063
      • US Renal Care
    • McAllen, Texas, United States, 78503
      • U.S. Renal Care
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • San Antonio Kidney Disease Center
    • San Antonio, Texas, United States, 78200
      • Dukes Carl
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital and Clinic
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Nephrology Associates of Northern Virginia
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater
    • Norfolk, Virginia, United States, 23502
      • Internal Medicine Kidney and Hypertension Center
    • Virginia Beach, Virginia, United States, 23455
      • Tidewater Kidney Specialists
  • Washington
    • Seattle, Washington, United States, 98133
      • Northwest Kidney Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	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.
Experimental: Magnesium iron hydroxycarbonate	Drug: 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.; Other Names: Alpharen, magnesium iron hydroxycarbonate
Active Comparator: Lanthanum carbonate	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.; Other Names: Fosrenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Stage 1: Control or not the level of serum phosphate	Within the treatment period
Stage 2: Change from treated baseline in mean serum phosphate	At 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Stage 1: Change from baseline in mean serum phosphate	End of 3 months treatment in maintenance period
Stage 1: Change from baseline in calcium, calcium phosphate product and PTH level	End of 3 months treatment in maintenance period
Stage 2: Change from treated baseline in mean serum phosphate	At weeks 1, 2 and 3
Stage 2: Change from treated baseline in Ca, Ca-phosphate product and PTH levels	At the end of weeks 1, 2, 3 and 4

Collaborators and Investigators

• Sponsor: Ineos Healthcare Limited
• Investigators: Study Chair: Information at Ineos Healthcare Limited (Chief Medical Officer), INEOS Healthcare Ltd, UK

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Anticipated): July 1, 2011
• Study Completion (Anticipated): July 1, 2011

Study Registration Dates

• First Submitted: February 10, 2009
• First Submitted That Met QC Criteria: February 10, 2009
• First Posted (Estimate): February 11, 2009

Study Record Updates

• Last Update Posted (Estimate): October 19, 2010
• Last Update Submitted That Met QC Criteria: October 18, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Hyperphosphatemia; Phosphate binder
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Phosphorus Metabolism Disorders; Kidney Failure, Chronic; Renal Insufficiency; Hyperphosphatemia; Physiological Effects of Drugs; Trace Elements; Micronutrients; Iron
• Other Study ID Numbers: ACT 401; 2008-004729-41 (EudraCT Number)