Oxazyme in Patients With Hyperoxaluria

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01127087
• Collaborator: OxThera (Industry)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperoxaluria	Drug: Oxazyme	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Evaluate the Safety and Efficacy of Oxazyme (OC4) in Patients With Hyperoxaluria
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Urinary Oxalate Creatinine Ratio [Baseline, Week 4]

   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.

Secondary Outcome Measures

1. Total Urinary Oxalate Excretion [Baseline, 4 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• OxThera

Investigators

• Principal Investigator: John Lieske, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Lieske, Professor of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01127087
• Other Study ID Numbers: 10-000676
• First Posted: May 20, 2010
• Last Update Posted: Dec 24, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by John Lieske, Professor of Medicine, Mayo Clinic: Hyperoxaluria; Oxazyme; oxalate; enteric hyperoxaluria

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the Mayo Clinic, Rochester, Minnesota.
Pre-assignment Detail	7 subjects were enrolled on the Idiopathic arm; of these 2 did not complete baseline collections, and 3 didn't qualify, so these 5 were excluded. 15 subjects were enrolled on the RYGB arm; of these, 3 never started the study and 2 did not qualify, so these 5 were excluded.

Arm/Group Title	RYGB CaOx Stone Formers	Idiopathic Hyperoxaluria CaOx Stone Formers
Arm/Group Description	Subjects with enteric hyperoxaluria after Roux-en-Y Gastric Bypass (RYGB). Dosing: 1gm Oxazyme containing approximately 1600 Units oxalate decarboxylase (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.	Subjects with idiopathic hyperoxaluria. Dosing: 1gm Oxazyme containing approximately 1600 Units oxalate decarboxylase (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.
Period Title: Overall Study
STARTED	8	2
COMPLETED	8	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	RYGB CaOx Stone Formers	Idiopathic Hyperoxaluria CaOx Stone Formers	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	8	2	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 75%	2 100%	8 80%
>=65 years	2 25%	0 0%	2 20%
Sex: Female, Male (Count of Participants)
Female	5 62.5%	0 0%	5 50%
Male	3 37.5%	2 100%	5 50%
Region of Enrollment (participants) [Number]
United States	8 100%	2 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Urinary Oxalate Creatinine Ratio
Description	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.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RYGB CaOx Stone Formers	Idiopathic Hyperoxaluria CaOx Stone Formers
Arm/Group Description	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.	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.
Measure Participants	8	2
Baseline	68.6 (36.4)	38.7 (6.9)
Week 4	49.6 (27.9)	34.7 (6.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RYGB CaOx Stone Formers
	Comments	Comparison of Urinary oxalate before and at the end of 4 weeks on Oxazyme in the RYGB Calcium oxalate (CaOx) Stone Formers arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Idiopathic Hyperoxaluria CaOx Stone Formers
	Comments	Comparison of Urinary oxalate before and at the end of 4 weeks on Oxazyme in the Idiopathic Hyperoxaluria CaOx Stone Formers arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Total Urinary Oxalate Excretion
Description	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.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RYGB CaOx Stone Formers	Idiopathic Hyperoxaluria CaOx Stone Formers
Arm/Group Description	Subjects with enteric hyperoxaluria after Roux-en-Y Gastric Bypass (RYGB). Dosing: 1gm Oxazyme containing approximately 1600 Units oxalate decarboxylase (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.	Subjects with idiopathic hyperoxaluria. Dosing: 1gm Oxazyme containing approximately 1600 Units oxalate decarboxylase (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.
Measure Participants	8	2
Baseline	66.3 (28.0)	43.2 (5.9)
4 Weeks	44.5 (23.7)	32.3 (3.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RYGB CaOx Stone Formers
	Comments	Comparison of Oxalate before and at the end of 4 weeks on Oxazyme in the RYGB CaOx Stone Formers arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Idiopathic Hyperoxaluria CaOx Stone Formers
	Comments	Comparison of Oxalate before and at the end of 4 weeks on Oxazyme in the Idiopathic Hyperoxaluria CaOx Stone Formers arm.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	The subjects were assessed for adverse events at each site visit and phone follow-up visit.
Arm/Group Title	RYGB CaOx Stone Formers		Idiopathic Hyperoxaluria CaOx Stone Formers
Arm/Group Description	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.		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.
All Cause Mortality
	RYGB CaOx Stone Formers		Idiopathic Hyperoxaluria CaOx Stone Formers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	RYGB CaOx Stone Formers		Idiopathic Hyperoxaluria CaOx Stone Formers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	RYGB CaOx Stone Formers		Idiopathic Hyperoxaluria CaOx Stone Formers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.