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Febuxostat Versus Allopurinol or Placebo in Patients With Hyperuricosuria and Calcium Oxalate Stones

Primary Purpose

Hyperuricosuria, Kidney Stones

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Febuxostat
Allopurinol
Placebo
Sponsored by
Takeda
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperuricosuria focused on measuring Kidney Calculi, Kidney Stones, Nephrolithiasis, Drug Therapy, Uric Acid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Has hyperuricosuria, defined as a daily urine uric acid excretion greater than 700 mg as measured by 24-hour urine collection prior to randomization.
  • Has at least one calcium oxalate stone greater than or equal to 3 mm in its longest in-plane diameter, identified by Multiple Detector Computated Tomography prior to randomization.
  • Has a recent (within the previous 5 years) history of renal stones prior to screening.

Exclusion Criteria:

  • Has gout, secondary hyperuricemia or has experienced a gout flare.
  • Has a history of xanthinuria.
  • Has received allopurinol or probenecid within 2 years prior to randomization.
  • Has received febuxostat.
  • Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal at the Screening Visit.
  • Has an abnormal serum calcium level at the Screening Visit.
  • Has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol according to the judgment of the Investigator.
  • Has a history of drug abuse or a history of alcohol abuse within 5 years prior to the Screening Visit.
  • Participant's measured creatinine clearance is less than 30 mL/min at the Screening Visit.

  • Has hypercalciuria at Screening, while on a regular unrestricted diet, defined as urinary excretion of:

    • greater than 250 mg of calcium/24-hour for females of body weight less than 62.5 kg; OR
    • greater than 300 mg calcium/24-hour for males of body weight less than 75 kg; OR
    • greater than 4 mg calcium/kg/24-hour for males of body weight greater than or equal 75 kg and females of body weight greater than or equal 62.5 kg.

EXCLUDED MEDICATIONS:

  • Febuxostat, allopurinol, probenecid.
  • Salicylates (chronic use of aspirin ≤325 mg/day is allowed).
  • Azathioprine.
  • Mercaptopurine.
  • Theophylline.
  • Colchicine.
  • Pyrazinamide.
  • Sulfamethoxazole/trimethoprim.
  • Losartan.

The following restrictions also apply during the study:

  • Long-term use (more than 4 continuous weeks) of prescription or over-the-counter nonsterioidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors.
  • If receiving diuretics, participant must have been on a stable dose for at least 30 days prior to screening. No changes in dosage are allowed during the study.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Febuxostat

Allopurinol

Placebo

Arm Description

Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.

Allopurinol 200mg or 300mg (determined by kidney function), capsules, orally, once daily for up to 6 months.

Placebo-matching capsules, orally, once daily for up to 6 months.

Outcomes

Primary Outcome Measures

Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
The change from Baseline to Month 6 in 24-hour urine uric acid is expressed as a percentage of the Baseline uUA value.

Secondary Outcome Measures

Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
Multidetector Computed Tomography (MDCT) was used to visualize and measure calcium oxalate kidney stones at Baseline and after 6 months of treatment. All MDCT images were analyzed independently by a Central Reader. The change from Baseline to month 6 is expressed as a percentage of the Baseline largest in-plane diameter.
Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
Multidetector Computed Tomography (MDCT) was used to visualize and count calcium oxalate kidney stones at Baseline and after 6 months of treatment. All MDCT images were analyzed independently by a Central Reader.
Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
Creatinine clearance is a measure of how well the kidneys are filtering creatinine, a waste product produced by the muscles. Measured creatinine clearance was calculated according to the following: Urine 24 hour Creatinine/Serum Creatinine x (total Urine volume/elapsed time) x (1.73/body surface area).

Full Information

First Posted
February 25, 2010
Last Updated
January 14, 2013
Sponsor
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT01077284
Brief Title
Febuxostat Versus Allopurinol or Placebo in Patients With Hyperuricosuria and Calcium Oxalate Stones
Official Title
A Multicenter, Randomized, Double-Blind, Placebo and Allopurinol Controlled, Phase 2 Study to Evaluate Febuxostat in the Medical Management of Subjects With Hyperuricosuria and Calcium Oxalate Stones
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
February 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the efficacy of febuxostat, once daily (QD), compared to allopurinol or placebo in patients with excessive amounts of uric acid in their urine and who have recently had kidney stones.
Detailed Description
Nephrolithiasis, also called kidney stone disease, occurs in patients with genetic susceptibility and who may have a broad spectrum of metabolic disorders and other comorbid conditions (for example obesity or diabetes). These renal stones develop as a result of supersaturation. Calcium oxalate (CaOx) is the most common type of stone. Reducing the urinary excretion of uric acid is an established approach for the treatment of CaOx kidney stones. The objective of this study is to evaluate treatment with febuxostat compared to allopurinol or placebo in the reduction of 24-hour urine uric acid (uUA) excretion levels in hyperuricosuric patients with a recent history of renal stones and the presence of at least one CaOx stone larger than or equal to 3 mm as seen on Multidetector Computed Tomographic Angiography (MDCT). Participants in this study will be required to make 4 office visits provide 3 urine samples and undergo 2 MDCT scans (a type of x-ray) of their kidneys.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperuricosuria, Kidney Stones
Keywords
Kidney Calculi, Kidney Stones, Nephrolithiasis, Drug Therapy, Uric Acid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
99 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Febuxostat
Arm Type
Experimental
Arm Description
Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.
Arm Title
Allopurinol
Arm Type
Active Comparator
Arm Description
Allopurinol 200mg or 300mg (determined by kidney function), capsules, orally, once daily for up to 6 months.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo-matching capsules, orally, once daily for up to 6 months.
Intervention Type
Drug
Intervention Name(s)
Febuxostat
Other Intervention Name(s)
Uloric, TMX-67
Intervention Description
Febuxostat capsules
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Other Intervention Name(s)
Zyloprim
Intervention Description
Allopurinol capsules
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo-matching capsules
Primary Outcome Measure Information:
Title
Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
Description
The change from Baseline to Month 6 in 24-hour urine uric acid is expressed as a percentage of the Baseline uUA value.
Time Frame
Baseline and Month 6
Secondary Outcome Measure Information:
Title
Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
Description
Multidetector Computed Tomography (MDCT) was used to visualize and measure calcium oxalate kidney stones at Baseline and after 6 months of treatment. All MDCT images were analyzed independently by a Central Reader. The change from Baseline to month 6 is expressed as a percentage of the Baseline largest in-plane diameter.
Time Frame
Baseline and Month 6
Title
Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
Description
Multidetector Computed Tomography (MDCT) was used to visualize and count calcium oxalate kidney stones at Baseline and after 6 months of treatment. All MDCT images were analyzed independently by a Central Reader.
Time Frame
Baseline and Month 6
Title
Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
Description
Creatinine clearance is a measure of how well the kidneys are filtering creatinine, a waste product produced by the muscles. Measured creatinine clearance was calculated according to the following: Urine 24 hour Creatinine/Serum Creatinine x (total Urine volume/elapsed time) x (1.73/body surface area).
Time Frame
Baseline and Month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has hyperuricosuria, defined as a daily urine uric acid excretion greater than 700 mg as measured by 24-hour urine collection prior to randomization. Has at least one calcium oxalate stone greater than or equal to 3 mm in its longest in-plane diameter, identified by Multiple Detector Computated Tomography prior to randomization. Has a recent (within the previous 5 years) history of renal stones prior to screening. Exclusion Criteria: Has gout, secondary hyperuricemia or has experienced a gout flare. Has a history of xanthinuria. Has received allopurinol or probenecid within 2 years prior to randomization. Has received febuxostat. Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal at the Screening Visit. Has an abnormal serum calcium level at the Screening Visit. Has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol according to the judgment of the Investigator. Has a history of drug abuse or a history of alcohol abuse within 5 years prior to the Screening Visit. Participant's measured creatinine clearance is less than 30 mL/min at the Screening Visit. Has hypercalciuria at Screening, while on a regular unrestricted diet, defined as urinary excretion of: greater than 250 mg of calcium/24-hour for females of body weight less than 62.5 kg; OR greater than 300 mg calcium/24-hour for males of body weight less than 75 kg; OR greater than 4 mg calcium/kg/24-hour for males of body weight greater than or equal 75 kg and females of body weight greater than or equal 62.5 kg. EXCLUDED MEDICATIONS: Febuxostat, allopurinol, probenecid. Salicylates (chronic use of aspirin ≤325 mg/day is allowed). Azathioprine. Mercaptopurine. Theophylline. Colchicine. Pyrazinamide. Sulfamethoxazole/trimethoprim. Losartan. The following restrictions also apply during the study: Long-term use (more than 4 continuous weeks) of prescription or over-the-counter nonsterioidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. If receiving diuretics, participant must have been on a stable dose for at least 30 days prior to screening. No changes in dosage are allowed during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Senior Medical Director Clinical Science
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Anchorage
State/Province
Alaska
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Costa Mesa
State/Province
California
Country
United States
City
Orange
State/Province
California
Country
United States
City
Palmdale
State/Province
California
Country
United States
City
Poway
State/Province
California
Country
United States
City
Rancho Cucamonga
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Santa Ana
State/Province
California
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
New Britain
State/Province
Connecticut
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Augusta
State/Province
Georgia
Country
United States
City
Honolulu
State/Province
Hawaii
Country
United States
City
Boise
State/Province
Idaho
Country
United States
City
Meridian
State/Province
Idaho
Country
United States
City
Lexington
State/Province
Kentucky
Country
United States
City
Kalamazoo
State/Province
Michigan
Country
United States
City
Jackson
State/Province
Mississippi
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
New Windsor
State/Province
New York
Country
United States
City
Shelby
State/Province
North Carolina
Country
United States
City
Wilmington
State/Province
North Carolina
Country
United States
City
East Providence
State/Province
Rhode Island
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Sugar Land
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23929928
Citation
Goldfarb DS, MacDonald PA, Gunawardhana L, Chefo S, McLean L. Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones. Clin J Am Soc Nephrol. 2013 Nov;8(11):1960-7. doi: 10.2215/CJN.01760213. Epub 2013 Aug 8.
Results Reference
derived
Links:
URL
http://general.takedapharm.com/content/file.aspx?applicationcode=6C7C39D8-5D09-453B-BF30-696A4AB88E62&fileTypeCode=ULORICPI
Description
Uloric Package Insert

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Febuxostat Versus Allopurinol or Placebo in Patients With Hyperuricosuria and Calcium Oxalate Stones

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