Oxazyme in Patients With Hyperoxaluria

Study Overview
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Brief Summary
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Hypothesis: Oral administration of the oxalate metabolizing enzyme Oxazyme (OC4) will degrade food-borne oxalate and hence prevent its absorption from the gastrointestinal tract. In addition, by reducing oxalate concentrations in the gastrointestinal fluid, oxalate secretion from blood to the intestinal tract may be increased. Both effects would decrease blood levels of oxalate, and hence oxalate excretion in the urine.

Detailed Description
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Oxazyme is an oxalate degrading compound that can potentially degrade food-borne oxalate and hence prevent its absorption from the gastrointestinal tract. We propose a 20-patient open-label trial pilot study of one month of Oxazyme twice daily (1gm Oxazyme sachet dissolved in 150 ml water) among adult subjects with a history of calcium oxalate nephrolithiasis. Patients will be stratified into those with enteric hyperoxaluria after Roux-en-Y Gastric Bypass (RYGB, n=10) and those with idiopathic hyperoxaluria (n=10). The patients will perform two, 24-hour, urine collections immediately before starting Oxazyme and on the last two days of the treatment period.

Official Title
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A Pilot Study to Evaluate the Safety and Efficacy of Oxazyme (OC4) in Patients With Hyperoxaluria

Conditions
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Hyperoxaluria

Intervention / Treatment
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* Drug: Oxazyme


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Roux-en-Y gastric bypass hyperoxaluric Calcium oxalate (CaOx) stone subjects or Idiopathic hyperoxaluric CaOx stone subjects Patients must have or had radio-opaque stones present on x-ray, or a history consistent with the passage of a stone or stone surgery or Extracorporeal Shock Wave Lithotripsy (ESWL) in the last 5 years. Hyperoxaluria Ox/Cr ratio ≥36 mg/g The patient must be able to provide written informed consent Patients must be able to urinate reliably into a collection vessel to measure urine volume. Patients may be taking drugs for the prevention of stone disease, including pyridoxine, thiazides, citrate supplements and allopurinol, as long as there have been no changes in these medications for at least 3 months Exclusion Criteria: Primary hyperoxaluria patients Use of Oxadrop, Oxabsorb, or other therapies affecting oxalate absorption from the gut, other than stable doses of calcium. Subjects who are pregnant. Women of childbearing potential must have a negative pregnancy test prior to enrollment and must practice some form of birth control during the trial. Patients on an unstable dose of any other drugs for the prevention of stone disease (i.e., pyridoxine, citrate supplements. etc.). Patients should have been on a stable dose for at least 3 months prior to randomization.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RYGB CaOx Stone Formers<br>Subjects with enteric hyperoxaluria after Roux-en-Y Gastric Bypass (RYGB). Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily. | Drug: Oxazyme<br>* Oxazyme (registered trademark) is a non-systemic orally delivered drug composed of recombinant oxalate decarboxylase (OxDC). It is formulated to enzymatically degrade available dietary oxalate prior to its absorption. Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily.<br>* Other names: OC4;|
| Experimental: Idiopathic Hyperoxaluria CaOx Stone Formers<br>Subjects with idiopathic hyperoxaluria. Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily. | Drug: Oxazyme<br>* Oxazyme (registered trademark) is a non-systemic orally delivered drug composed of recombinant oxalate decarboxylase (OxDC). It is formulated to enzymatically degrade available dietary oxalate prior to its absorption. Dosing: 1gm Oxazyme containing approximately 1600 Units OxDC in a sachet administered BID together with lunch and dinner. Subjects were instructed to open the oxazyme sachets and either sprinkle on food or add to a glass of water or fruit juice and consume the contents with a meal twice daily.<br>* Other names: OC4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary Oxalate Creatinine Ratio | The urinary oxalate per creatinine ratio is expressed as mg/g. Paired t-test will be used when comparing reduction of urinary oxalate resulting from treatment (versus baseline) for each subject group. | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Urinary Oxalate Excretion | Oxalate is a salt of oxalic acid produced by the body's metabolism and excreted in the urine, measured in this study in two, 24-hour, urine collections. | Baseline, 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperoxaluria, Oxazyme, oxalate, enteric hyperoxaluria