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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01077284
First received: February 25, 2010
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Hyperuricosuria
Kidney Stones
Drug: Febuxostat
Drug: Allopurinol
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 6 ] [ Designated as safety issue: No ]
    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).


Enrollment: 99
Study Start Date: February 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077284

  Show 28 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Senior Medical Director Clinical Science Takeda
  More Information

Additional Information:
No publications provided by Takeda

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01077284     History of Changes
Other Study ID Numbers: TMX-67_201, U1111-1113-6322
Study First Received: February 25, 2010
Results First Received: October 15, 2012
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Kidney Calculi
Kidney Stones
Nephrolithiasis
Drug Therapy
Uric Acid

Additional relevant MeSH terms:
Calculi
Kidney Calculi
Nephrolithiasis
Kidney Diseases
Pathological Conditions, Anatomical
Urinary Calculi
Urolithiasis
Urologic Diseases
Allopurinol
Febuxostat
Antimetabolites
Antioxidants
Antirheumatic Agents
Enzyme Inhibitors
Free Radical Scavengers
Gout Suppressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014