Effects of Lanthanum Carbonate on FGF-23 in Subjects With Stage 3 CKD

A Proof of Concept, Phase 2a, Double-blind, Parallel Group, Randomised, Placebo-controlled Study to Assess the Effect of Lanthanum Carbonate on Intact FGF23 in Normo-phosphataemic Subjects With Stage 3 Chronic Kidney Disease

To assess the effects of 12 weeks of treatment with lanthanum carbonate compared with placebo on serum intact Fibroblast Growth Factor 23 (FGF23) levels.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Lanthanum carbonate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris
    • Saint Ouen, Paris, France, 93400
      • Dr Pablo Urena Torres

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 Criteria:

Subjects meeting all of the criteria listed below may be included in the study:

1. ≥18 years old.
2. Male, or non-pregnant, non-lactating females who agree to comply with any applicable contraceptive requirements of the protocol.
3. Been in the care of a physician for CKD for >2 months, and are not expected to begin dialysis for at least 6 months.
4. Screening serum c-terminal FGF23 > 50.0RU/mL.
5. Screening estimated glomerular filtration rate (eGFR) of 30-59mL/min/1.73m2 using the MDRD formula.
6. Normal serum phosphate (0.808-1.55mmol/L).
7. Endogenous 25-hydroxy Vitamin D levels >20ng/mL.
8. Adequate protein diet (includes 2-3 portions of protein-rich food per day).
9. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
10. Ability to provide written, signed, and dated (personally) informed consent to participate in the study.

Exclusion Criteria

1. Vitamin D supplementation required.
2. Compounds containing calcium, phosphate, aluminium or magnesium required.
3. Acute renal failure.
4. Rapidly progressing glomerulonephritis.
5. Vegetarian diet.
6. Known allergy to iodine.
7. Clinically significant uncontrolled concurrent illness, which, in the opinion of the Investigator, would impair subjects' ability to give informed consent or take part in or complete this clinical study.
8. Cirrhosis or other clinically significant liver disease (aspartate transaminase (AST) or alanine transaminase (ALT) >3 times the upper limit of normal or bilirubin >2 times the upper limit of normal).
9. Past (treated within the last 5 years) or present GI disorders including uncontrolled peptic ulcer, Crohn's disease (or other conditions where the integrity of the GI tract may be compromised), malignancy, or GI bleed within the last 6 months.
10. Life-threatening malignancy or current multiple myeloma.
11. Known to be Human Immunodeficiency Virus (HIV) positive.
12. History of poor compliance with diet or medication that in the Investigator's opinion may interfere with adherence to the protocol.
13. History of alcohol or other substance abuse within 6 months prior to screening.
14. Subjects must not have used another investigational medicinal product or taken part in a clinical trial within the last 30 days prior to enrolment.
15. Subjects who have previously been enrolled into this study and subsequently withdrawn.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo chewable tablets administered 3 times a day for 12 weeks
Experimental: Lanthanum carbonate	Drug: Lanthanum carbonate; 1000 mg in chewable tablets administered three times a day (for a total of 3000 mg/day) for 12 weeks; Other Names: Fosrenol/Foznol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural Logarithm Transformed Serum Intact Fibroblast Growth Factor (FGF-23) Levels at Week 12 Last Observation Carried Forward (LOCF)	FGF-23 plays an important role in mineral metabolism in chronic kidney disease patients. It is secreted by bone cells in response to hyperphosphatemia. It acts to decrease renal phosphate reabsorption. Administration of a phosphate-binder (i.e. lanthanum carbonate) was expected to produce a reduction in FGF-23 levels.	12 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Serum Intact Parathyroid Hormone (iPTH) Values at Week 12 (LOCF)	12 Weeks
Change From Baseline in 1,25-Dihydroxy Vitamin D Values at Week 12 (LOCF)	12 weeks
Change From Baseline in Urinary Fractional Excretion of Phosphate Values at Week 12 (LOCF)	12 weeks
Change From Baseline in Serum Phosphate Values at Week 12 (LOCF)	12 weeks
Change From Baseline in Serum Total Calcium Values at Week 12 (LOCF)	12 weeks
Change From Baseline in Calcium-Phosphate Product Values at Week 12 (LOCF)	12 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Urena-Torres P, Prie D, Keddad K, Preston P, Wilde P, Wan H, Copley JB. Changes in fibroblast growth factor 23 levels in normophosphatemic patients with chronic kidney disease stage 3 treated with lanthanum carbonate: results of the PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial. BMC Nephrol. 2014 May 5;15:71. doi: 10.1186/1471-2369-15-71.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2010
• Primary Completion (Actual): April 16, 2012
• Study Completion (Actual): April 16, 2012

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (Estimate): May 21, 2010

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: SPD405-703; 2009-016531-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No