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

Sponsor

Universitair Ziekenhuis Brussel (Other)

Overall Status

Recruiting

CT.gov ID

NCT03346369

Collaborator

(none)

Enrollment

Location

Arm

64.4

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Secondary Hyperoxaluria Nephrolithiasis	Drug: Lanthanum Carbonate	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 18, 2017

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental single arm 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 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

Arm

Intervention/Treatment

Experimental: Experimental single arm

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

Outcome Measures

Primary Outcome Measures

The mean reduction in urinary oxalate excretion in patients treated with a daily Lanthanum Carbonate dose of 750 mg [After the first 14-day treatment period]
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.

Secondary Outcome Measures

The incremental reduction in mean urinary oxalate excretion after doubling the dose of Lanthanum Carbonate from 750 mg tot 1500 mg daily [After the second 14-day treatment period]
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
The proportion of patients developing severe hypophosphatemia [After the first and second 14-day treatment period]
Severe hypophosphatemia is defined as serum phosphorus < 0.64 mmol/L
The evolution of phosphaturia, evaluated by 24-hour urinary phosphorus excretion [After the first and second 14-day treatment period]
24-hour urinary phosphorus excretion will be expressed in mmol/24 hours
The evolution of phosphaturia, evaluated by urinary phosphorus to creatinine ratio [After the first and second 14-day treatment period]
Urinary phosphorus to creatinine ratio will be expressed in mmol phosphorus/g creatinine
The evolution of phosphaturia, evaluated by fractional excretion of phosphorus [After the first and second 14-day treatment period]
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))
The proportion of patients developing hypophosphaturia [After the first and second 14-day treatment period]
Hypophosphaturia is defined as urinary phosphorus < 12.9 mmol/24 hours
The evolution of calciuria, evaluated by 24-hour urinary calcium excretion [After the first and second 14-day treatment period]
24-hour urinary calcium excretion will be expressed in mmol/24 hours
The evolution of calciuria, evaluated by urinary calcium to creatinine ratio [After the first and second 14-day treatment period]
Urinary calcium to creatinine ratio will be expressed in mmol calcium/g creatinine
The evolution of calciuria, evaluated by fractional excretion of calcium [After the first and second 14-day treatment period]
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))
The evolution of serum Lanthanum levels [After the first and second 14-day treatment period]
Serum Lanthanum levels will be expressed in mcg/L
Adverse events [After the first and second 14-day treatment period]
The number and the proportion of patients experiencing adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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