Effect of Febuxostat on Renal Function in Patients With Gout and Moderate to Severe Renal Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01082640
First received: March 5, 2010
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to determine the effect of febuxostat, once daily (QD) or twice daily (BID), on renal function in gout patients with elevated serum urate levels and who have moderate to severe renal impairment.


Condition Intervention Phase
Renal Impairment
Drug: Febuxostat
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, Phase 2 Study to Evaluate the Effect of Febuxostat Versus Placebo on Renal Function in Gout Subjects With Hyperuricemia and Moderate to Severe Renal Impairment

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Change From Baseline to Month 12 in Serum Creatinine [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.


Secondary Outcome Measures:
  • Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline and Month 12 ] [ Designated as safety issue: No ]
    Change from baseline to Month 12 in estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula (as calculated by the central laboratory).

  • Percentage of Participants With Serum Urate (sUA) Less Than 6 mg/dL at Month 12 [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Serum urate concentrations were determined using the enzymatic method as performed by the Central Laboratory.

  • Mean Clearance (CL/F) of Febuxostat at Steady State [ Time Frame: The 2 pre-dose PK samples collected were collected at any 2 of the following visits: Months 3, 6, 9, and/or 12, at -0.25 to 0 hours. The 4 postdose PK samples were collected at Months 3, 6, and/or 9, at 0.25; 0.75 to 2.0; 2.5 to 4.0; and 5 to 12 hours. ] [ Designated as safety issue: No ]
    Mean CL/F at steady state were estimated using a population pharmacokinetic (PK) approach, based on 2 PK samples collected prior to dosing, and 4 PK samples collected postdose.

  • Mean Area Under the Concentration-Time Curve During the Dosing Interval (AUC[0-τ]) of Febuxostat at Steady State [ Time Frame: The 2 pre-dose PK samples collected were collected at any 2 of the following visits: Months 3, 6, 9, and/or 12, at -0.25 to 0 hours. The 4 postdose PK samples were collected at Months 3, 6, and/or 9, at 0.25; 0.75 to 2.0; 2.5 to 4.0; and 5 to 12 hours. ] [ Designated as safety issue: No ]
    Mean AUC during the dosing interval at steady state was estimated using a population pharmacokinetic (PK) approach, based on 2 PK samples collected prior to dosing, and 4 PK samples collected postdose.


Enrollment: 96
Study Start Date: April 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo-matching capsules, orally, twice daily for up to 12 months.
Drug: Placebo
Febuxostat placebo-matching capsules
Experimental: Febuxostat 30 mg BID
Febuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months.
Drug: Febuxostat
Febuxostat capsules
Other Names:
  • Uloric
  • TMX-67
Experimental: Febuxostat 40/80 mg QD
Participants initially received febuxostat 40 mg, capsules, once daily (QD) and one placebo-matching capsule QD and remained on this dose for up to 12 months if their serum urate (sUA) was <6.0 mg/dL at the Day 14 visit. Participants whose sUA was ≥6.0 mg/dL at the Day 14 visit received febuxostat 80 mg, capsule, QD, and one placebo-matching capsule QD at the Month 1 visit, and for the remainder of the study.
Drug: Febuxostat
Febuxostat capsules
Other Names:
  • Uloric
  • TMX-67
Drug: Placebo
Febuxostat placebo-matching capsules

Detailed Description:

Gout is caused by high levels of uric acid in the body, and is associated with a broad range of conditions including heart disease, chronic kidney disease and high blood pressure. Hyperuricemia, which is defined as an elevation in serum urate levels, develops into gout when urate crystals form in the body and settle in joints and other organs.

Approximately 40-60% of patients with hyperuricemia and gout have some degree of renal impairment. Hyperuricemia has long been associated with renal disease, and chronic hyperuricemia as seen in gout can lead to deposition of urate crystals resulting in diminished renal function.

This study will evaluate the effect of febuxostat on the renal function of patients with hyperuricemia and gout and moderate to severe renal impairment.

All participants must have an average sitting blood pressure measurement less than 160 mmHg systolic and less than 95 mmHg diastolic. All participants must meet the American Rheumatism Association (ARA) diagnostic criteria for gout (subjects with tophi were excluded). Participants are expected to return to the site for approximately 10 visits.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a serum urate greater than 7 mg/dL and a serum creatinine greater than or equal to 1.5 mg at Day -21
  • Must have a history or presence of gout defined as having one or more of the American Rheumatism Association criteria for the diagnosis of gout (the criteria related to tophi have been excluded for the purpose of the study)
  • Must have an estimated Glomerular Filtration Rate (eGFR) of 15 or greater, or less than or equal to 50 mL/min, AND a serum creatinine greater than 1.5 mg/dL at Screening Visit Day -21

Exclusion Criteria:

  • Has secondary hyperuricemia (eg, due to myeloproliferative disorder, or organ transplant)
  • Has tophaceous gout
  • Has a history of xanthinuria
  • Has received aspirin greater than 325 mg/day within 35 days prior to Day 1/Randomization Visit
  • Has known hypersensitivity or allergy to allopurinol or any component in its formulation
  • Has known hypersensitivity to febuxostat or colchicine or any components in their formulation
  • Has myocardial infarction or stroke within the 90 days prior to the Screening Visit
  • Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal
  • Has end stage renal disease or is likely to be a candidate for dialysis over the 1 year study period
  • Has a serum creatinine less than or equal to 1.5 mg/dL, or an estimated Glomerular Filtration Rate at Day -21 Screening Visit less than 15 mL/min or greater than 50 mL/min as calculated by the central laboratory
  • Is required to take excluded medications
  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: NCT01082640

  Show 58 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01082640     History of Changes
Other Study ID Numbers: TMX-67_203, U1111-1113-8008
Study First Received: March 5, 2010
Results First Received: May 31, 2013
Last Updated: September 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Takeda:
Gout
physiology
Hyperuricemia
Uric Acid
Drug Therapy

Additional relevant MeSH terms:
Renal Insufficiency
Hyperuricemia
Kidney Diseases
Urologic Diseases
Pathologic Processes
Febuxostat
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014