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

NCT ID: NCT01077284

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2011-11-30

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.

Conditions

Hyperuricosuria; Kidney Stones

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Febuxostat

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

Group Type: EXPERIMENTAL

Febuxostat

Intervention Type: DRUG

Febuxostat capsules

Allopurinol

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

Group Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

Allopurinol capsules

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo-matching capsules

Interventions

Febuxostat

Febuxostat capsules

Intervention Type: DRUG

Allopurinol

Allopurinol capsules

Intervention Type: DRUG

Placebo

Placebo-matching capsules

Intervention Type: DRUG

Other Intervention Names

Uloric; TMX-67; Zyloprim

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senior Medical Director Clinical Science

Role: STUDY_DIRECTOR

Takeda

Locations

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

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 23929928 (View on PubMed)

Related Links

http://general.takedapharm.com/content/file.aspx?applicationcode=6C7C39D8-5D09-453B-BF30-696A4AB88E62&fileTypeCode=ULORICPI

Uloric Package Insert

Other Identifiers

U1111-1113-6322

Identifier Type: REGISTRY

Identifier Source: secondary_id

TMX-67_201

Identifier Type: -

Identifier Source: org_study_id