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

Nephrolithiasis Clinical Trial

— LaCa  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03346369
• Other study ID #: oxalate01
• Status: Recruiting
• Phase: Phase 3
• Start date: August 18, 2017
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2021
• Source: Universitair Ziekenhuis Brussel
• Contact: Celine Olbrechts, Study Coordinator
• Phone: +32 (0)2 477 62 24
• Email: Celine.Olbrechts[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperoxaluria
• Kidney Calculi
• Neoplasm Metastasis
• Nephrolithiasis
• Secondary Hyperoxaluria

Intervention

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

Locations

Country	Name	City	State
Belgium	University Hospital Brussels	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The evolution of serum Lanthanum levels	Serum Lanthanum levels will be expressed in mcg/L	After the first and second 14-day treatment period
Secondary	Adverse events	The number and the proportion of patients experiencing adverse events	After the first and second 14-day treatment period