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Phase 2 N=99 Randomized Quadruple-blind Treatment

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

Hyperuricosuria · Kidney Stones

Enrolled (actual)
99
Serious AEs
1.0%
Results posted
Feb 2013
Primary outcome: Primary: Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion — -58.6; -36.4; -12.7 percent change — p=<0.001

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Febuxostat (Drug); Allopurinol (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Takeda
Primary completion
Nov 2011

Outcome Measures

OutcomeResultp-value
PRIMARY
Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
-58.6; -36.4; -12.7 <0.001 sig
SECONDARY
Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
-6.50; 0.63; 3.20 0.130
SECONDARY
Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
4.84; 6.60; 5.57; -0.06; 0.28; 0.10 0.403
SECONDARY
Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
146.9; 146.0; 147.1; -9.0; -7.7; -19.0 0.5535

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.

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01077284). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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