Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis

Study Overview
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Brief Summary
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This study investigates the efficacy and the safety of Lanthanum Carbonate for the reduction of urinary oxalate excretion in patients with secondary hyperoxaluria and nephrolithiasis.

Detailed Description
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Nephrolithiasis/urolithiasis is a prevalent (overall lifetime risk up to 13% in Western countries) and highly recurrent disease. Secondary hyperoxaluria is a key risk factor for the development of calcium oxalate stones, the most frequent stone type. Currently used therapeutic options in secondary hyperoxaluria have limited efficacy. Recent findings in vitro and in a rat model, provided evidence that Lanthanum Carbonate is an effective oxalate binder. The objective of this study is to investigate whether treatment with Lanthanum Carbonate reduces urinary oxalate excretion in human subjects with secondary hyperoxaluria and nephrolithiasis. By treating the patients with two different doses of Lanthanum Carbonate during two 14-day treatment periods, a dose-response will be evaluated.

Official Title
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Lanthanum Carbonate (Fosrenol®) to Reduce Oxalate Excretion in Patients With Secondary Hyperoxaluria and Nephrolithiasis: a Short-term, Prospective, Open-label, Efficacy and Safety Clinical Trial

Conditions
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Secondary Hyperoxaluria, Nephrolithiasis

Intervention / Treatment
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* Drug: Lanthanum Carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: able to give written informed consenct hyperoxaluria (defined as urinary oxalate > 45 mg/24 hours), demonstrated on 24-hour urine collection within 18 months prior to baseline visit history of nephrolithiasis eGFR > 60 mL/min/1.73m² (CKD-EPI formula) Exclusion Criteria: primary hyperoxaluria, diagnosed by genetic testing known allergy to Lanthanum Carbonate hypophosphatemia (defined as serum phosphorus < 0.81 mmol/L) severe known liver insufficiency of biliary obstruction rectocolitis ulcerohaemorraghica, Crohn's disease, bowel obstruction, stomach/duodenal ulceration glucose/galactose malabsorption severe diarrhea or other gastrointestinal disorder, which might interfere with the ability to absorb oral medication pregnancy or breast-feeding female participant of childbearing potential unwilling to take efficient contraceptive measures for the duration of the study female participant without negative serum or urine pregnancy test psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study currently participating in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This study investigates the efficacy and the safety of Lanthanum Carbonate for the reduction of urinary oxalate excretion in patients with secondary hyperoxaluria and nephrolithiasis. Patients will be treated during 2 consecutive 14-day treatment periods with a low and a high dose of Lanthanum Carbonate respectively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental single arm<br>Treatment with Lanthanum Carbonate 3 x 250 mg/day with meals during a first 14-day treatment period. Subsequently, treatment with Lanthanum Carbonate 3 x 500 mg/day with meals during a second 14-day treatment period. | Drug: Lanthanum Carbonate<br>* Treatment with Lanthanum Carbonate 3 x 250 mg/day with meals during a first 14-day treatment period. Subsequently, treatment with Lanthanum Carbonate 3 x 500 mg/day with meals during a second 14-day treatment period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean reduction in urinary oxalate excretion in patients treated with a daily Lanthanum Carbonate dose of 750 mg | Mean reduction in urinary oxalate excretion after the first 14-day treatment period during which patients will be treated with 250 mg Lanthanum Carbonate 3x/day with meals, expressed in mg oxalate/g creatinine. | After the first 14-day treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incremental reduction in mean urinary oxalate excretion after doubling the dose of Lanthanum Carbonate from 750 mg tot 1500 mg daily | Incremental reduction of mean urinary oxalate excretion after the second 14-day treatment period during which the patients will be treated with 500 mg Lanthanum Carbonate 3x/day with meals, expressed in mg oxalate/g creatinine | After the second 14-day treatment period | 
| The proportion of patients developing severe hypophosphatemia | Severe hypophosphatemia is defined as serum phosphorus < 0.64 mmol/L | After the first and second 14-day treatment period | 
| The evolution of phosphaturia, evaluated by 24-hour urinary phosphorus excretion | 24-hour urinary phosphorus excretion will be expressed in mmol/24 hours | After the first and second 14-day treatment period | 
| The evolution of phosphaturia, evaluated by urinary phosphorus to creatinine ratio | Urinary phosphorus to creatinine ratio will be expressed in mmol phosphorus/g creatinine | After the first and second 14-day treatment period | 
| The evolution of phosphaturia, evaluated by fractional excretion of phosphorus | Fractional excretion of phosphorus will be expressed in %, defined as (urinary phosphorus (mmol/L) x serum creatinine (mg/dL) / (serum phosphorus (mmol/L) x urine creatinine (mg/dL)) | After the first and second 14-day treatment period | 
| The proportion of patients developing hypophosphaturia | Hypophosphaturia is defined as urinary phosphorus < 12.9 mmol/24 hours | After the first and second 14-day treatment period | 
| The evolution of calciuria, evaluated by 24-hour urinary calcium excretion | 24-hour urinary calcium excretion will be expressed in mmol/24 hours | After the first and second 14-day treatment period | 
| The evolution of calciuria, evaluated by urinary calcium to creatinine ratio | Urinary calcium to creatinine ratio will be expressed in mmol calcium/g creatinine | After the first and second 14-day treatment period | 
| The evolution of calciuria, evaluated by fractional excretion of calcium | Fractional excretion of calcium will be expressed in %, defined as (urinary calcium (mmol/L) x serum creatinine (mg/dL)) / (serum calcium (mmol/L) x urine creatinine (mg/dL)) | After the first and second 14-day treatment period | 
| The evolution of serum Lanthanum levels | Serum Lanthanum levels will be expressed in mcg/L | After the first and second 14-day treatment period | 
| Adverse events | The number and the proportion of patients experiencing adverse events | After the first and second 14-day treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperoxaluria, Nephrolithiasis, Urolithiasis, Secondary Hyperoxaluria, Lanthanum Carbonate, Phosphate Binder