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

Chronic Kidney Failure Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00841126
• Other study ID #: ACT 401
• Secondary ID: 2008-004729-41
• Status: Terminated
• Phase: Phase 3
• First received: February 10, 2009
• Last updated: October 18, 2010
• Start date: July 2009
• Est. completion date: July 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 AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationSouth Africa: Medicines Control CouncilCanada: Health CanadaPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsGermany: Federal Institute for Drugs and Medical DevicesBrazil: National Health Surveillance AgencySpain: Spanish Agency of MedicinesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Malta: Medicines AuthorityNew Zealand: Medsafe
• 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 hemodialysis, compared with a marketed phosphate binder, lanthanum carbonate and placebo.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 657
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 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:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Hervey Bay Hospital	Pialba	Queensland
Australia	Epworth Hospital	Richmond	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	Hospital Universitario da Univ Federal de Juiz de Fora	Juiz de Fora	MG
Brazil	Hospital Universitario Pedro Ernesto	Rio de Janeiro	RJ
Brazil	Universidade Federal de Sao Paulo - UNIFESP	Sao Paulo	SP
Brazil	Faculdade de Ciencias Medicas de Sorocaba - Hosp Santa Lucin	Sorocaba	SP
Canada	William Osler Health Centre	Brampton	Ontario
Canada	Exsequi Recherche Clinique	Gatineau	Quebec
Canada	Hospital Charles LeMoyne	Greenfield Park	Quebec
Canada	Capital District Health Authority	Halifax	Nova Scotia
Canada	Clinical Research Solutions Inc.	Kitchener	Ontario
Canada	London Health Science Centre - University Campus Site	London	Ontario
Canada	Royal Victoria Hospital	Montréal	Quebec
Canada	St. Michael's Health Care Centre	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
France	Centre Hospitalier Sud	Amiens Cedex 1	80
France	Clinique Mutualiste des Eaux Claires	Grenoble	38
Germany	Gemeinschaftspraxis	Aschaffenburg	BY
Germany	Prager Gerhard	Bad Koenig	HE
Germany	Klinikum Coburg	Coburg	BY
Germany	Dialysepraxis Altona	Hamburg	HH
Germany	Dialysezentrum Barmbek	Hamburg	HH
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern	RP
Malta	Mater Dei Hospital Medical Outpatient	B'Kara
Malta	Mater Dei Hospital Renal Unit	B'Kara
Malta	Gozo General Hospital	Gozo
New Zealand	Auckland City Hospital	Auckland
New Zealand	Middlemore Hospital	Auckland
New Zealand	Wellington Hospital	Wellington
Poland	Szpital Specjalistyczny	Dabrowa Gornicza
Poland	NZOZ Avitum-Stacja Dializ Sp.z.o.o	Golub Dobrzyn
Poland	NZOZ Miedzynarodowe Centrum Dializ Poznan Odz. Rawicz	Rawicz
Poland	Euromedic NZOZ Miedzynarodowe	Wroclaw
Poland	NZOZ Miedzynarodowe Centrum Dializ	Wroclaw
South Africa	Netcare Private Hospital	Bloemfontein	Free State
South Africa	Entabeni Hospital	D'Urban	KZ-Natal
South Africa	St. Augustines Hospital	Durban	KZ-Natal
South Africa	Chris Hani Baragwanath Hospital	Johannesburg	Gauteng
Spain	H Clinic i Provincial	Barcelona
Spain	HU de Bellvitge	Barcelona
United States	U.S. Renal Care	Arlington	Texas
United States	Western Nephrology & Metabolic Bone Disease PC	Arvada	Colorado
United States	William Beaumont Hospitals	Berkley	Michigan
United States	Nephrology Associates PC	Birmingham	Alabama
United States	Brookdale Physicians Dialysis Associates	Brooklyn	New York
United States	Hypertension and Renal Research Group	Buffalo	New York
United States	U.S. Renal Care	Burleson	Texas
United States	Nephrology Associates	Chattanooga	Tennessee
United States	University of Cincinnati Medical Center	Cinncinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Nephrology Associates P.C.	Columbus	Mississippi
United States	South Florida Nephrology Group P.A.	Coral Springs	Florida
United States	St. Clair Specialty Physicians PC	Detroit	Michigan
United States	Research by Design LLC	Evergreen Park	Illinois
United States	Nephrology Associates of Northern Virginia	Fairfax	Virginia
United States	U.S. Renal Care	Fort Worth	Texas
United States	U.S. Renal Care	Fort Worth	Texas
United States	Texas Renal Care	Greenville	Texas
United States	North Suburban Nephrology	Gurnee	Illinois
United States	Ralph Plaza Nephrology	Houston	Texas
United States	Outcomes Research International Inc.	Hudson	Florida
United States	Dallas Nephrology Associates	Irving	Texas
United States	US Renal Care	Jonesboro	Arkansas
United States	Research Nurse Specialists LLC	Lafayette	Louisiana
United States	Hypertension and Kidney Specialists	Lancaster	Pennsylvania
United States	Kantor Nephrology Consultants Ltd.	Las Vagas	Nevada
United States	University of Southern California	Los Angeles	California
United States	Renal Physicians of Georgia PC	Macon	Georgia
United States	US Renal Care	Mansfield	Texas
United States	U.S. Renal Care	McAllen	Texas
United States	Boise Kidney & Hypertension Institute	Meridian	Idaho
United States	Nephrology Associates of South Miami	Miami	Florida
United States	Nephrology and Hypertension Associates	Middlebury	Connecticut
United States	Nephrology Associates	Nashville	Tennessee
United States	Lower Manhattan Dialysis Center	New York	New York
United States	Clinical Research Associates of Tidewater	Norfolk	Virginia
United States	Internal Medicine Kidney and Hypertension Center	Norfolk	Virginia
United States	Creighton University	Omaha	Nebraska
United States	SC Nephrology & Hypertension Center Inc.	Orangeburg	South Carolina
United States	Nephrology Associates Research Center	Panama City	Florida
United States	Arizona Kidney Disease and Hypertension Center	Phoenix	Arizona
United States	Wright Steven (Private Practice)	Pine Bluff	Arkansas
United States	Lazowski Piotr MD- PC	Plymouth	Massachusetts
United States	Long Island Hypertension and Nephrology PLLC	Port Washington	New York
United States	Wake Nephrology Associates PA	Raleigh	North Carolina
United States	Apex Research of Riverside	Riverside	California
United States	Dukes Carl	San Antonio	Texas
United States	San Antonio Kidney Disease Center	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	North America Research Institute	San Dimas	California
United States	Northwest Kidney Center	Seattle	Washington
United States	Kidney Center Inc.	Simi Valley	California
United States	Nephrology Educational Services and Research	Tarzana	California
United States	Southwest Kidney Institute	Tempe	Arizona
United States	Scott and White Memorial Hospital and Clinic	Temple	Texas
United States	Tidewater Kidney Specialists	Virginia Beach	Virginia
United States	Western Nephrology & Metabolic Bone Disease PC	Westminister	Colorado
United States	Cleveland Clinic Florida	Weston	Florida
United States	American Institute of Research	Whittier	California
United States	Kansas Nephrology Research Institute LLC	Wichita	Kansas
United States	Fallon Clinic - Winthrop	Worcester	Massachusetts
United States	North Valley Nephrology	Yoba City	California
United States	Humility of Mary Health Partners	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ineos Healthcare Limited

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Control or not the level of serum phosphate		Within the treatment period	Yes
Primary	Stage 2: Change from treated baseline in mean serum phosphate		At 4 weeks	Yes
Secondary	Stage 1: Change from baseline in mean serum phosphate		End of 3 months treatment in maintenance period	Yes
Secondary	Stage 1: Change from baseline in calcium, calcium phosphate product and PTH level		End of 3 months treatment in maintenance period	Yes
Secondary	Stage 2: Change from treated baseline in mean serum phosphate		At weeks 1, 2 and 3	Yes
Secondary	Stage 2: Change from treated baseline in Ca, Ca-phosphate product and PTH levels		At the end of weeks 1, 2, 3 and 4	Yes