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CompletedNCT01077284Updated Feb 15, 2013Results posted

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

A Phase 2 interventional study of Febuxostat and Allopurinol in Hyperuricosuria and Kidney Stones, sponsored by Takeda. Completed at 28 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-02-15.

Sponsored by Takeda · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
99
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Hyperuricosuria
  • Kidney Stones

Keywords

  • Kidney Calculi
  • Kidney Stones
  • Nephrolithiasis
  • Drug Therapy
  • Uric Acid
03

In context

Kidney Calculi

598 studies on the registry are indexed under Kidney Calculi; 163 are open to participants now.

This study's enrollment of 99 is close to the median of 90 across 461 interventional studies indexed under Kidney Calculi.

Browse Kidney Calculi studies →

Lead sponsor

Takeda is the lead sponsor of 1,002 studies on the registry; 92 are open to participants now.

Of its 173 completed or terminated interventional studies of FDA-regulated products, 149 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
99 participants (actual)

Study arms

  • Experimental
    Febuxostat

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

    Drug: Febuxostat

  • Active comparator
    Allopurinol

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

    Drug: Allopurinol

  • Placebo comparator
    Placebo

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

    Drug: Placebo

Interventions

  • DrugFebuxostat

    Febuxostat capsules

    Also known as: Uloric, TMX-67

  • DrugAllopurinol

    Allopurinol capsules

    Also known as: Zyloprim

  • DrugPlacebo

    Placebo-matching capsules

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and Month 6

Secondary outcomes

  1. 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.

    Time frame: Baseline and Month 6

  2. 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.

    Time frame: Baseline and Month 6

  3. 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).

    Time frame: Baseline and Month 6

07

Results

Posted Feb 15, 2013

Participant flow

Participants took part in the study at 24 investigative sites in the United States from 12 February 2010 to 21 November 2011.

Participant flow — Overall Study
MilestoneFebuxostatAllopurinolPlacebo
Started333333
Completed282830
Not completed553
Withdrew: Adverse event201
Withdrew: Lost to follow-up120
Withdrew: Withdrawal by subject231
Withdrew: Other001

Outcome measures

PrimaryPercent 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · percent change
Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
percent changeFebuxostatAllopurinolPlacebo
Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion-58.6 ± 28.56-36.4 ± 36.97-12.7 ± 28.81
Statistical analysis
  • Febuxostat vs Placebo · Wilcoxon (Mann-Whitney) · p = <0.001 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)
  • Febuxostat vs Allopurinol · Wilcoxon (Mann-Whitney) · p = 0.003 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)
SecondaryPercent 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · percent change
Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
percent changeFebuxostatAllopurinolPlacebo
Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone-6.50 ± 28.3570.63 ± 12.6053.20 ± 23.697
Statistical analysis
  • Febuxostat vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.130 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)
  • Febuxostat vs Allopurinol · Wilcoxon (Mann-Whitney) · p = 0.348 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)
SecondaryChange 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.

Time frame:
Baseline and Month 6
Reported as:
Mean · stones
Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
stonesFebuxostatAllopurinolPlacebo
Baseline (n=28, 24, 30)4.84 ± 3.9216.60 ± 6.8325.57 ± 5.785
Change from Baseline (n=26, 23, 26)-0.06 ± 1.6020.28 ± 1.9530.10 ± 1.817
Statistical analysis
  • Febuxostat vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.403 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)
  • Febuxostat vs Allopurinol · Wilcoxon (Mann-Whitney) · p = 0.413 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)
SecondaryChange 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).

Time frame:
Baseline and Month 6
Reported as:
Mean · mL/min/1.73m²
Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
mL/min/1.73m²FebuxostatAllopurinolPlacebo
Baseline (n=33, 33, 33)146.9 ± 57.88146.0 ± 44.32147.1 ± 53.46
Change from Baseline (n=30, 29, 30)-9.0 ± 60.82-7.7 ± 83.28-19.0 ± 45.72
Statistical analysis
  • Febuxostat vs Placebo · ANOVA · p = 0.5535 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)P-values are from ANOVA with treatment as a fixed effect.
  • Febuxostat vs Allopurinol · ANOVA · p = 0.9400 (Hochberg's method for multiple comparisons was used to ensure that the overall 0.050 level of significance was maintained for comparisons of febuxostat to allopurinol and to placebo.)P-values are from ANOVA with treatment as a fixed effect.

Adverse events

Collected over Treatment emergent AEs were defined as any AE, regardless of relationship to study drug, which occurred on or after the first double blind dose date and up to 30 days after the last dose date of the double-blind study drug (up to 7 months).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Febuxostat—0/33 (0%)14/33 (42.4%)
Allopurinol—0/33 (0%)13/33 (39.4%)
Placebo—1/33 (3%)12/33 (36.4%)
Most frequent serious events
Most frequent serious events
EventFebuxostatAllopurinolPlacebo
NephrolithiasisRenal and urinary disorders0/330/331/33
Most frequent other events
Showing 10 of 12
Most frequent other events
EventFebuxostatAllopurinolPlacebo
Flank painMusculoskeletal and connective tissue disorders4/330/332/33
Back painMusculoskeletal and connective tissue disorders1/333/331/33
Upper respiratory tract infectionInfections and infestations0/332/333/33
NephrolithiasisRenal and urinary disorders3/331/333/33
HeadacheNervous system disorders0/333/333/33
Oedema peripheralGeneral disorders1/333/331/33
Muscle spasmsMusculoskeletal and connective tissue disorders1/332/330/33
Blood creatine phosphokinase increasedInvestigations2/330/330/33
Creatinine urine increasedInvestigations2/330/330/33
Urine calcium increasedInvestigations2/331/330/33

Baseline characteristics

Age Continuous
Age Continuous(years)FebuxostatAllopurinolPlaceboTotal
Mean49.1 ± 9.6946.5 ± 9.9546.5 ± 11.5447.4 ± 10.39
Sex: Female, Male
Sex: Female, Male(Participants)FebuxostatAllopurinolPlaceboTotal
Female62614
Male27312785
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)FebuxostatAllopurinolPlaceboTotal
Hispanic or Latino88319
Non-Hispanic and Latino25253080
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)FebuxostatAllopurinolPlaceboTotal
Asian2024
Black or African American3115
Native Hawaiian or other Pacific Islander1012
White26312986
Other1102
Region of Enrollment
Region of Enrollment(participants)FebuxostatAllopurinolPlaceboTotal
United States33333399
Height
Height(cm)FebuxostatAllopurinolPlaceboTotal
Mean172.6 ± 12.67176.5 ± 7.71174.3 ± 9.31174.5 ± 10.14
Weight
Weight(kg)FebuxostatAllopurinolPlaceboTotal
Mean98.0 ± 18.17100.9 ± 20.13100.8 ± 20.2399.9 ± 19.38
Body mass index (BMI)
Body mass index (BMI)(kg/m^2)FebuxostatAllopurinolPlaceboTotal
Mean32.9 ± 5.7132.3 ± 5.8233.1 ± 6.2932.8 ± 5.89

13 further baseline measures are reported on the registry.

08

Study locations

28 sites
  • Birmingham, Alabama, United States
  • Anchorage, Alaska, United States
  • Tucson, Arizona, United States
  • 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
  • Denver, Colorado, United States
  • New Britain, Connecticut, United States
  • Miami, Florida, United States
  • Augusta, Georgia, United States
  • Honolulu, Hawaii, United States
  • Boise, Idaho, United States
  • Meridian, Idaho, United States
  • Lexington, Kentucky, United States
  • Kalamazoo, Michigan, United States
  • Jackson, Mississippi, United States
  • Albuquerque, New Mexico, United States
  • New Windsor, New York, United States
  • Shelby, North Carolina, United States
  • Wilmington, North Carolina, United States
  • East Providence, Rhode Island, United States
  • Dallas, Texas, United States
  • Houston, Texas, United States
  • Sugar Land, Texas, United States
09

References and documents

Publications

  • 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. PubMed 23929928 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 15, 2013, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01077284
Lead sponsor
Takeda
Responsible party
Sponsor
First posted
Mar 1, 2010
Start date
Feb 2010
Primary completion
Nov 2011
Completion
Nov 2011
Results posted
Feb 15, 2013
Last update
Feb 15, 2013

Study contacts

Senior Medical Director Clinical Science
study director · Takeda

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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