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

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ClinicalTrials.gov Identifier: NCT01077284
Recruitment Status : Completed
First Posted : March 1, 2010
Results First Posted : February 15, 2013
Last Update Posted : February 15, 2013
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hyperuricosuria Kidney Stones Drug: Febuxostat Drug: Allopurinol Drug: Placebo Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : February 2010
Actual Primary Completion Date : November 2011
Actual Study Completion Date : November 2011

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Febuxostat
Febuxostat 80 mg, capsules, orally, once daily for up to 6 months.
 Drug: Febuxostat
Febuxostat capsules
Other Names:
  • Uloric
  • TMX-67
Active Comparator: Allopurinol
Allopurinol 200mg or 300mg (determined by kidney function), capsules, orally, once daily for up to 6 months.
 Drug: Allopurinol
Allopurinol capsules
Other Name: Zyloprim
Placebo Comparator: Placebo
Placebo-matching capsules, orally, once daily for up to 6 months.
 Drug: Placebo
Placebo-matching capsules


Outcome Measures
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Primary Outcome Measures :
  1. Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion [ Time Frame: Baseline and Month 6 ]
    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 :
  1. Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone [ Time Frame: Baseline and Month 6 ]
    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.

  2. Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones [ Time Frame: Baseline and Month 6 ]
    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.

  3. Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance [ Time Frame: Baseline and Month 6 ]
    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).


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01077284


Locations
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United States, Alabama
Birmingham, Alabama, United States
United States, Alaska
Anchorage, Alaska, United States
United States, Arizona
Tucson, Arizona, United States
United States, California
Costa Mesa, California, United States
Orange, California, United States
Palmdale, California, United States
Poway, California, United States
Rancho Cucamonga, California, United States
San Diego, California, United States
Santa Ana, California, United States
United States, Colorado
Denver, Colorado, United States
United States, Connecticut
New Britain, Connecticut, United States
United States, Florida
Miami, Florida, United States
United States, Georgia
Augusta, Georgia, United States
United States, Hawaii
Honolulu, Hawaii, United States
United States, Idaho
Boise, Idaho, United States
Meridian, Idaho, United States
United States, Kentucky
Lexington, Kentucky, United States
United States, Michigan
Kalamazoo, Michigan, United States
United States, Mississippi
Jackson, Mississippi, United States
United States, New Mexico
Albuquerque, New Mexico, United States
United States, New York
New Windsor, New York, United States
United States, North Carolina
Shelby, North Carolina, United States
Wilmington, North Carolina, United States
United States, Rhode Island
East Providence, Rhode Island, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
Sugar Land, Texas, United States
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Senior Medical Director Clinical Science Takeda
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01077284    
Other Study ID Numbers: TMX-67_201
U1111-1113-6322 ( Registry Identifier: WHO )
First Posted: March 1, 2010    Key Record Dates
Results First Posted: February 15, 2013
Last Update Posted: February 15, 2013
Last Verified: January 2013
Keywords provided by Takeda:
Kidney Calculi
Kidney Stones
Nephrolithiasis
Drug Therapy
Uric Acid
Additional relevant MeSH terms:
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Kidney Calculi
Nephrolithiasis
Calculi
Pathological Conditions, Anatomical
Kidney Diseases
Urologic Diseases
Urolithiasis
Urinary Calculi
Allopurinol
Febuxostat
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs