Oxazyme in Patients With Hyperoxaluria

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperoxaluria
• Intervention / Treatment: Drug: Oxazyme

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RYGB CaOx Stone Formers; 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; 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.; Other Names: oxalate decarboxylase; OC4
Experimental: Idiopathic Hyperoxaluria CaOx Stone Formers; 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; 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.; Other Names: oxalate decarboxylase; OC4

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: OxThera

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: May 14, 2010
• First Submitted That Met QC Criteria: May 19, 2010
• First Posted (Estimate): May 20, 2010

Study Record Updates

• Last Update Posted (Estimate): December 24, 2012
• Last Update Submitted That Met QC Criteria: November 21, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: oxalate; Hyperoxaluria; enteric hyperoxaluria; Oxazyme
• Other Study ID Numbers: 10-000676