FGF23 Reduction : Efficacy of a New Phosphate Binder in CHronic Kidney Disease (FRENCH)

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier:
NCT01220843
First received: October 12, 2010
Last updated: September 2, 2013
Last verified: February 2012
  Purpose

The purpose of this study is to evaluate in Chronic Kidney Disease (CKD) patients not on dialysis and who have an Fibroblast growth factor 23 (FGF23) serum levels elevated, the effect of non calcic phosphate binder: sevelamer carbonate. This treatment could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate. In addition, the investigators will describe the impact of the FGF23 level monitoring on the main phosphocalcium metabolism markers as phosphatemia, intact parathyroid hormone (iPTH), serum calcitriol and phosphaturia.


Condition Intervention Phase
Chronic Renal Failure
Drug: Placebo
Drug: Sevelamer carbonate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Placebo Controlled Double-blind Trial in CKD Patients Not on Dialysis to Evaluate the Effect of Sevelamer Carbonate in the Control of FGF-23 Serum Levels and Its Consequences in the Evolution of PTH, Calcitriol and Mineral Metabolism Parameters Levels

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire, Amiens:

Primary Outcome Measures:
  • Measurement of the serum levels of C terminal segment of fibroblast growth factor 23 (FGF23) and evaluation of sevelamer carbonate effect on this levels in comparison with placebo [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
    Indeed the sevelamer carbonate could lead to a diminution of FGF23 serum levels due to the diminution of intestinal absorption of dietary phosphate.


Secondary Outcome Measures:
  • Evaluation of sevelamer carbonate effect on the serum levels of iPTH [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the serum levels of calcitriol (1 25(OH)2D3) [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the serum levels of others mineral metabolism parameters (phosphore, calcium, intact FGF-23 , 25(OH)D3, bone specific alkaline phosphatases, osteocalcin, collagen crosslink, C reactive protein) [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the urinary levels of phosphate [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the urinary levels of calcium [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the urinary levels of creatinine [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the urinary levels of urea [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]
  • Evaluation of sevelamer carbonate effect on the serum and urinary levels of specific biomarkers (serum : fetuin A, para-cresyl sulfate, osteopontin) [ Time Frame: 12 weeks after the beginning of treatment ] [ Designated as safety issue: No ]

Enrollment: 98
Study Start Date: October 2010
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
DOuble blinded, same labels than the active drug same dosage (2 tablets 3 times per day) during the meal
Drug: Placebo
dosage : 2 tablets 3 times per day corresponding taken during meals during 12 weeks
Other Name: Placebo
Experimental: Sevelamer carbonate
DOuble blinded, dosage 2 tablets 3 times per day corresponding to 4.8/d to taken during meals
Drug: Sevelamer carbonate
dosage : 2 tablets 3 times per day corresponding taken during meals during 12 weeks ( each tablet :800mg sevelamer carbonate
Other Name: Renvela 800

Detailed Description:

The total length of the study is 14 weeks divided in 2 parts the first part is the screening period she will stay 1 to 2 weeks and the second period with the treatment with permanent dosage during 12 weeks.

During the screening visit (Vo) inclusion and non inclusion criteria will be checked and the patient consent will be collected. Biological analysis will be performed.

If the patient still eligible after the reception of biological results, he will be randomized and will received, either sevelamer carbonate, either placebo. The study treatment will be begun at the randomisation visit (V1) the dosage will be 2 tablets 3 times per day (corresponding to 4.8g/d sevelamer carbonate for patient taken active medication).

Patient will be seen every 2 weeks after the first visit (+/-5days) during 6 weeks (visit2/day15, visit3/day30, visit4/day45) and 12 weeks after the randomisation visit (visit5/day90). This visits will include biological analysis, compliance evaluation, adverse events report, concomitant treatments reports.

After the consent signature, all the adverse events will be collected until the end of the study for the patient (Visit5 or end of the study visit). Serious adverse events will be collected until 30 days after the date of the end of the study.

The same dosage of the study treatment will be followed during all the study period except if the phosphatemia (evaluated during one analysis) is found above the normal range planned by the protocol. In this case, the dosage adaptations will be :

  • If during a visit the phosphatemia is above or equal to 0.8 mmol/l and superior to 0.5 mmol/l, the study treatment dosage need to be reduce to 2 tablets 3 times per day to 1 tablet 3 times per day.
  • If during the next blood punction, the phosphatemia still or equal to 0.8 mmol/l and superior to 0.5 mmol/l, the study treatment will be stopped and a "end of study" visit will be performed.
  • If during one study visit, the phosphatemia is above or equal to 0.5 mmol/l,the study treatment will be stopped immediately and a end of study visit will be performed.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who gave their written consent
  • Women or men over 18 years
  • No concomitant treatment with phosphate binders
  • CKD patients not on dialysis stage 3b or 4, as a GFR (glomerular filtration rate) between 15 and 45 ml/min/1.73m2, using simplified MDRD formula
  • At the inclusion visit,patients with blood results as levels of C-terminal FGF-23 > 120 rU/ml and fasting phosphatemia > 1.0 mmol/l
  • Able to comply with the study procedures during all the study period
  • Willing to abstain from taking any following medication during all the study period :antiacid and phosphate binders with aluminium, magnesium, calcium or lanthanum;Treatment for hyperparathyroid : active vitamin D and calcimimetic ; native vitamin D
  • Female subjects who are of childbearing potential must have a reliable contraceptive methods during all the study period (hormonal, barrier methods or intrauterine device)
  • No Participation in any clinical trial using an investigational product or device during the 30 days preceding the first protocol visit
  • Informed patient who agreed with the utilisation of his data for the study
  • Able to read and understand french and study objectives
  • Inscription to medical assurance

Exclusion Criteria:

  • predisposition with or presence of intestinal or ileus obstruction or severe gastrointestinal motility disorder(like severe constipation)
  • Antecedent of major gastrointestinal surgery
  • Abusive consumption of alcohol and drug (exclude tabacco) according the investigator
  • Arrythmia treated by antiarrythmic agent or epilepsia treated by anticonvulsant
  • Antecedent of kidney transplantation
  • Antecedent of parathyroidectomy
  • At the inclusion visit,patients with blood results as fasting phosphatemia > 1.78 mmol/l or serum 25(OH)D3< 20 ng/ml (<50 nmol/)
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01220843

Locations
France
CHU Amiens service de nephrologie
Amiens, France, 8000
CHU de Bordeaux Service de néphrologie
Bordeaux, France, 33076
CHU Caen service de néphrologie
Caen, France, 14033
CHU Lyon service de néphrologie
Lyon, France, 69437
CHU Marseille Service de néphrologie
Marseille, France, 13385
CHU de Montpellier Hôpital Lapeyronie Service de Néphrologie
Montpellier, France, 34295
CHU de Nice Service de néphrologie
Nice, France, 06002
Hôpital Européen Georges Pompidou Service de Nephrologie
Paris, France, 75098
Hôpital Tenon Service de Nephrologie
Paris, France, 75020
CHU Reims service de néphrologie
Reims, France, 51092
Clinique du Landy Centre de dialyse
Saint Ouen, France, 93400
CHU St Etienne Hopital Nord Service de néphrologie
St Etienne, France, 42055
Néphrologie - Dialyse Centre de Rein Artificiel
TASSIN la Demi Lune, France, 69160
CH Valenciennes hémodialyse
Valenciennes, France, 59322
CHU de Nancy service de néphrologie
Vandeuvre les Nancy, France, 54511
Sponsors and Collaborators
Centre Hospitalier Universitaire, Amiens
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Gabriel Choukroun, Ph D, M D Centre Hospitalier Universitaire, Amiens
  More Information

Publications:
JP Cristol, AS Bargnoux, AM Dupuy, M Morena, A Avignon and B Canaud. Biological markers of vascular calcifications in uremia. Médecine Nucléaire 2009; 33, 53-61.

Responsible Party: Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier: NCT01220843     History of Changes
Other Study ID Numbers: Amiens FRENCH, 2010-020872-49
Study First Received: October 12, 2010
Last Updated: September 2, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Hospitalier Universitaire, Amiens:
chronic renal failure
FGF23
Sevelamer carbonate

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Sevelamer
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents

ClinicalTrials.gov processed this record on October 23, 2014