Clinical trial NCT01077284: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperuricosuria
Kidney Stones
Keywords: Kidney Calculi
Kidney Stones
Nephrolithiasis
Drug Therapy
Uric Acid
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-03-01
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
timeFrame: Baseline and Month 6
measure: Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
timeFrame: Baseline and Month 6
measure: Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
timeFrame: Baseline and Month 6
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Anchorage
country: United States
state: Alaska
city: Tucson
country: United States
state: Arizona
city: Costa Mesa
country: United States
state: California
city: Orange
country: United States
state: California
city: Palmdale
country: United States
state: California
city: Poway
country: United States
state: California
city: Rancho Cucamonga
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: New Britain
country: United States
state: Connecticut
city: Miami
country: United States
state: Florida
city: Augusta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Boise
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Lexington
country: United States
state: Kentucky
city: Kalamazoo
country: United States
state: Michigan
city: Jackson
country: United States
state: Mississippi
city: Albuquerque
country: United States
state: New Mexico
city: New Windsor
country: United States
state: New York
city: Shelby
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: East Providence
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
Study officials:
affiliation: Takeda
name: Senior Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
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.