Renal ImpairmentPhase 2NCT01082640

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

A Phase 2 study testing Febuxostat in people with Renal Impairment, run by Takeda at 58 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Renal Impairment
What is being tested?: Febuxostat
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 96 participants
Where: 58 sitesUnited States
Study dates: Apr 2010to May 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

58 sites in 1 country.

City, postcode or hospital

58 sites in 1 country

United States58 sites

Study site
Anderson, South Carolina
Study site
Arvada, Colorado
Study site
Augusta, Georgia
Study site
Baltimore, Maryland
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Bethlehem, Pennsylvania
Study site
Birmingham, Alabama
Study site
Boise, Idaho
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Brandon, Florida
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Brooklyn Center, Minnesota
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Chattanooga, Tennessee
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Clarksburg, West Virginia
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Conyers, Georgia
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Danville, Virginia
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Daytona Beach, Florida
Study site
Detroit, Michigan
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Dunwoody, Georgia
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Elizabethtown, Kentucky
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Evergreen Park, Illinois
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Fairfax, Virginia
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Fargo, North Dakota
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Greer, South Carolina
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Honolulu, Hawaii
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Houston, Texas
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Huntington Park, California
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Irvine, California
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Jacksonville, Florida
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Kalamazoo, Michigan
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Lakewood, California
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Little Rock, Arkansas
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Long Beach, California
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Miami, Florida
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Middlebury, Connecticut
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Morganton, North Carolina
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Neptune City, New Jersey
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Odessa, Texas
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Oklahoma City, Oklahoma
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Paducah, Kentucky
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Peoria, Arizona
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Pinellas Park, Florida
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Port Charlotte, Florida
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Port Orange, Florida
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Portland, Oregon
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Richmond, Virginia
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Sacramento, California
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San Antonio, Texas
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San Diego, California
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San Jose, California
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Sierra Vista, Arizona
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Springfield, Illinois
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Tucson, Arizona
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Tustin, California
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Valparaiso, Indiana
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Wauwatosa, Wisconsin
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Westminster, Colorado
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Wheat Ridge, Colorado
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Wichita, Kansas
Study site
Williamsburg, Virginia
Study site
Wilmington, North Carolina

Other trials in United States

About this study

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

Read the 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.

Conditions: Renal Impairment
Being tested: Febuxostat, Placebo
Keywords: Gout, physiology, Hyperuricemia, Uric Acid, Drug Therapy
Medical subject headings: Renal Insufficiency, Gout, Hyperuricemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FebuxostatDrug
Also called Uloric, TMX-67
Febuxostat capsules
PlaceboDrug
Febuxostat placebo-matching capsules

Study groups in NCT01082640
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo-matching capsules, orally, twice daily for up to 12 months. Receives: Drug: Placebo
Febuxostat 30 mg BID	Experimental	Febuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months. Receives: Drug: Febuxostat
Febuxostat 40/80 mg QD	Experimental	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. Receives: Drug: Febuxostat; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline to Month 12 in Serum Creatinine
Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.
Measured: Baseline and Month 12

Secondary outcomes (4)

Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
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).
Measured: Baseline and Month 12
Percentage of Participants With Serum Urate (sUA) Less Than 6 mg/dL at Month 12
Serum urate concentrations were determined using the enzymatic method as performed by the Central Laboratory.
Measured: Month 12
Mean Clearance (CL/F) of Febuxostat at Steady State
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.
Measured: 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.
Mean Area Under the Concentration-Time Curve During the Dosing Interval (AUC[0-τ]) of Febuxostat at Steady State
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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2010May 2012

First posted8 Mar 2010 (estimated)
Study startApr 2010
Primary completionMay 2012
Study completionMay 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 96 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01082640
Sponsor's protocol ID: TMX-67_203
Other IDs: U1111-1113-8008
Status last verified: Sep 2013
First submitted: 5 Mar 2010
Last updated: 25 Sep 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Saag KG, Whelton A, Becker MA, MacDonald P, Hunt B, Gunawardhana L. Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. Arthritis Rheumatol. 2016 Aug;68(8):2035-43. doi: 10.1002/art.39654.
PubMed 26894653

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01082640
Acronym / sponsor ID: TMX-67_203
Conditions: Renal Impairment
Keywords: Gout, physiology, Hyperuricemia, Uric Acid, Drug Therapy
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 96 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Apr 2010
Primary completion: May 2012 (actual)
Study completion: May 2012 (actual)
First posted: 8 Mar 2010 (estimated)
Results: Posted 25 Sep 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlaceboPlacebo-matching capsules, orally, twice daily for up to 12 months.
Febuxostat 30 mg BID	Experimental	Drug: FebuxostatFebuxostat 30 mg, capsules, orally, twice daily (BID) for up to 12 months.
Febuxostat 40/80 mg QD	Experimental	Drug: Febuxostat, Drug: PlaceboParticipants 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FebuxostatAlso: Uloric, TMX-67Febuxostat capsules	Drug	Febuxostat 30 mg BID, Febuxostat 40/80 mg QD
PlaceboFebuxostat placebo-matching capsules	Drug	Febuxostat 40/80 mg QD, Placebo

Primary outcome

Change From Baseline to Month 12 in Serum Creatinine
Time frame: Baseline and Month 12
Renal function was assessed by measuring the change from Baseline in serum creatinine. Analyses were conducted by the Central Laboratory.

4 secondary outcomes

Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline and Month 12
Percentage of Participants With Serum Urate (sUA) Less Than 6 mg/dL at Month 12
Time frame: Month 12
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.
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.

Results and safety

Results posted to the registry on 25 Sep 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	32	15
Febuxostat 30 mg BID	32	17
Febuxostat 40/80 mg QD	32	24

Primary outcome: Change From Baseline to Month 12 in Serum Creatinine

Time frame: Baseline and Month 12. Least squares mean (Standard Error). Unit: mg/dL

Measure	Placebo n = 32	Febuxostat 30 mg BID n = 32	Febuxostat 40/80 mg QD n = 31
Baseline	2.52 (0.126)	2.10 (0.126)	2.22 (0.128)
Change from Baseline at Month 12	0.19 (0.094)	0.09 (0.093)	0.23 (0.094)

Placebo vs Febuxostat 30 mg BID: LS mean difference: -0.10 (95% CI -0.37 to 0.17), p = 0.459, ANCOVA
Placebo vs Febuxostat 40/80 mg QD: LS mean difference: 0.04 (95% CI -0.23 to 0.30), p = 0.789, ANCOVA

Population analysed: Full analysis set, including all patients who were randomized and received at least 1 dose of double-blind study medication. Only patients with both a baseline value and at least 1 value during the double-blind treatment period are included in the analysis. Missing data were imputed as carrying forward the last observed post-baseline value.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first double-blind dose date and up to 30 days after the last dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	7 of 32 (21.9%)	20 of 32 (62.5%)	Not reported
Febuxostat 30 mg BID	5 of 32 (15.6%)	21 of 32 (65.6%)	Not reported
Febuxostat 40/80 mg QD	8 of 32 (25%)	23 of 32 (71.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26894653Saag KG, Whelton A, Becker MA, MacDonald P, Hunt B, Gunawardhana L. Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment. Arthritis Rheumatol. 2016 Aug;68(8):2035-43. doi: 10.1002/art.39654.
Uloric Package InsertLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Takeda

58 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Febuxostat in people with Renal Impairment, run by Takeda at 58 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Month 12 in Serum Creatinine (time frame: Baseline and Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01082640, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2013.