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Joint DamagePhase 2NCT01078389

Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout

A Phase 2 study testing Febuxostat in people with Joint Damage, run by Takeda at 56 sites in United States.

Completed

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

Official record
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Trial summary

This purpose of this study is to assess the effect of febuxostat, once daily (QD), on joint damage in patients with elevated serum urate levels and gout. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Joint Damage
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
314 participants
Where
56 sitesUnited States
Study dates
Mar 2010to Sep 2013
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

  • The participant, or the participant's legally acceptable representative, signs a written informed consent form/Health Insurance Portability \& Accountability Act (HIPAA) Authorization prior to the initiation of any study procedures.
  • Must have a history or presence of gout defined as having one or more of the following conditions of the American Rheumatism Association (ARA) preliminary criteria for the diagnosis of gout
  • A tophus proven to contain urate crystals by chemical or polarized light microscopic means and/or
  • Characteristic urate crystals in the joint fluid and/or
  • History of at least 6 of the following clinical, laboratory and x-ray phenomena*: *More than one flare criteria will be excluded for the purpose of this study if the participant has a history of only a single acute gout flare.
  • More than one attack of acute arthritis*
Show all 24Show fewer
  • maximum inflammation developed within 1 day
  • monoarticular arthritis
  • redness observed over joints
  • first metatarsophalangeal joint painful or swollen
  • unilateral first metatarsophalangeal joint attack
  • unilateral tarsal joint attack
  • tophus (proven or suspected)
  • hyperuricemia
  • asymmetric swelling within a joint on x-ray
  • sub-cortical cysts without erosions on x-ray
  • joint fluid culture negative for organisms during attacks
  • *More than one flare criteria will be excluded for the purpose of this study if the participant has a history of only a single acute gout flare.
  • Is male and at least 18 years of age OR;
  • Female ≥45 years of age and at least 2 years post-menopausal AND has a Follicle Stimulating Hormone (FSH) level ≥40 IU/L OR
  • Female receiving hormone replacement therapy (HRT) must be ≥55 years of age (FSH level not required).
  • Has hyperuricemia defined as serum Uric Acid (sUA) level ≥7.0 mg/dL at Screening.
  • Has a history of ≤2 (1 or 2) flares. In participants with a history of 2 flares, must have had only one flare in any 12 month period. The primary affected joint will be based on the location of the first gout flare which must be located within right or left metatarsophalangeal (MTP), interphalangeal (IP), ankle, metacarpophalangeal (MCP), Proximal Inter-Phalangeal (PIP), or distal inter-phalangeal (DIP) joints prior to Screening.
  • Is capable of understanding and complying with protocol requirements, including scheduled clinic procedures.

Who cannot join

  • Previously on urate-lowering therapy (allopurinol, febuxostat or probenecid).
  • Has secondary hyperuricemia (eg due to myeloproliferative disorder or organ transplant).
  • Has a history of xanthinuria.
  • Has a known hypersensitivity to any component of the febuxostat formulation.
  • Has rheumatoid arthritis.
  • Has active peptic ulcer disease.
Show all 24Show fewer
  • Has a history of cancer, except basal cell carcinoma of the skin, which has not been in remission for at least 5 years prior to the first dose of study medication.
  • Has experienced either a myocardial infarction (MI) or stroke within 90 days prior to the Screening visit.
  • Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) values greater than 2.0 the upper limit of normal during the Screening period.
  • Has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol at the discretion of the Investigator.
  • Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse with 5 years prior to the Screening visit. Participant consumes >14 alcoholic beverages/week.
  • Has received any investigational medicinal product within 30 days prior to the Screening visit. In addition, the participant has been previously randomized into this study and received at least one dose of double blind study drug treatment.
  • Has an estimated Glomerular filtration rate (eGFR) <60 mL/min calculated using the Modification of Diet in Renal Disease (MDRD) formula by the Central Laboratory.
  • Has a serum creatinine at Screening greater than 2.0 mg/dL.
  • Has a known history of infection with hepatitis B, hepatitis C or human immunodeficiency virus.
  • Is a study site employee, or is an immediate family member (ie, spouse, parent, child, and sibling) of a study site employee involved in conduct of this study.
  • Is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent form is available.
  • Is required to take excluded medications.
  • Magnetic Resolution Imaging:
  • Has a known hypersensitivity to gadolinium
  • Has history of severe asthma
  • Has an electronically, magnetically or mechanically activated implanted device
  • Has any object that could present a potential hazard or interfere with MRI interpretation secondary to the artifact (i.e. metallic foreign bodies)
  • Has a significant medical condition considered by the Investigator (or radiologist) to interfere with the participant's ability to receive gadolinium (eg Sickle cell anemia).

Trial locations and contacts

56 sites in 1 country.

56 sites in 1 country

United States56 sites

  • Study site

    Albuquerque, New Mexico

  • Study site

    Arlington, Virginia

  • Study site

    Arlington Heights, Illinois

  • Study site

    Austin, Texas

  • Study site

    Avon, Indiana

  • Study site

    Bellevue, Nebraska

  • Study site

    Belzoni, Mississippi

  • Study site

    Billings, Montana

  • Study site

    Boynton Beach, Florida

  • Study site

    Burbank, California

  • Study site

    Burke, Virginia

  • Study site

    Carmichael, California

  • Study site

    Charlotte, North Carolina

  • Study site

    Chaska, Minnesota

  • Study site

    Columbia, South Carolina

  • Study site

    Costa Mesa, California

  • Study site

    Dayton, Ohio

  • Study site

    Daytona Beach, Florida

  • Study site

    Duncansville, Pennsylvania

  • Study site

    East Providence, Rhode Island

  • Study site

    Eugene, Oregon

  • Study site

    Fort Lauderdale, Florida

  • Study site

    Franklin, Ohio

  • Study site

    Greenfield, Indiana

  • Study site

    Henderson, Nevada

  • Study site

    Hialeah, Florida

  • Study site

    Honolulu, Hawaii

  • Study site

    Houston, Texas

  • Study site

    Irvine, California

  • Study site

    Kenosha, Wisconsin

  • Study site

    Kingsport, Tennessee

  • Study site

    Las Vegas, Nevada

  • Study site

    Lenoir, North Carolina

  • Study site

    Manassas, Virginia

  • Study site

    Mesa, Arizona

  • Study site

    Miami, Florida

  • Study site

    Missoula, Montana

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Olive Branch, Mississippi

  • Study site

    Orange, California

  • Study site

    Rancho Cucamonga, California

  • Study site

    Rapid City, South Dakota

  • Study site

    Rockport, Maine

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    San Luis Obispo, California

  • Study site

    Sanford, Florida

  • Study site

    Shelby, North Carolina

  • Study site

    Southlake, Texas

  • Study site

    Sugar Land, Texas

  • Study site

    Tampa, Florida

  • Study site

    Trumbull, Connecticut

  • Study site

    Tucson, Arizona

  • Study site

    Wichita, Kansas

  • Study site

    Willoughby Hills, Ohio

  • Study site

    Winter Park, Florida

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 in Joint Damage in Hyperuricemic Subjects With Early Gout

This purpose of this study is to assess the effect of febuxostat, once daily (QD), on joint damage in patients with elevated serum urate levels and gout.

Read the detailed description

Gout is caused by high levels of uric acid in the body, and is associated with a broad range of comorbidities including heart disease, chronic kidney disease and additional risk factors like obesity and high blood pressure. Hyperuricemia, which is defined as an elevation in serum urate levels, develops into gout when urate crystals form from supersaturated body fluids and settle in joints and other organs. Urate-lowering therapy is used to treat hyperuricemia in patients with gout.

Current treatments focus on initiating urate-lowering therapy in hyperuricemic gout patients who have experienced multiple acute gout flares within the past year. However, joint damage caused by crystal deposition may occur much earlier than previously considered. Monosodium urate crystals have been found present in the joints of people with hyperuricemia who do not have any symptoms. The presence of monosodium urate crystals would indicate that after the crystals form, they stay within the joint if serum urate levels are not reduced. Lowering uric acid levels and maintaining them may reduce acute gout flare episodes and possibly halt or reduce joint damage in patients with gout.

This study will evaluate the effect of febuxostat on joint damage in hyperuricemic patients with early gout. All patients will receive gout flare prophylaxis for the first 6 months of the study. Gout flares may also be treated throughout the study.

A variety of imaging techniques are in use to evaluate gout. Plain radiographs (x-rays), Magnetic Resonance Imaging (MRI) and Dual Energy Computed Tomography (DECT) will be utilized in this study. The modified Sharp/Van Der Heijde scoring method (named after Drs. Sharp and Van Der Heijde) for assessment of x-rays has been validated in patients with chronic gout and will be used in this study for evaluating erosion and joint space narrowing. Participants are expected to have 15 visits which will include plain radiographic examinations at 5 visits, 3 Magnetic Resonance Imaging (MRI) examinations and 3 DECT procedures at selected sites.

Conditions
Joint Damage
Being tested
Febuxostat, Placebo for Febuxostat
Keywords
Gout, Hyperuricemia, Uric Acid, Drug Therapy
Medical subject headings
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

  • Placebo for FebuxostatDrug

    Febuxostat placebo-matching capsules

Study groups in NCT01078389
Study groupRoleWhat they receive
Febuxostat 40 mg or 80 mgExperimentalFebuxostat 40 mg or 80 mg (based on serum urate levels at Day 14), capsules, orally, once daily for up to 24 Months.
Receives: Drug: Febuxostat
PlaceboPlacebo comparatorFebuxostat placebo-matching capsules, orally, once daily for up to 24 Months.
Receives: Drug: Placebo for Febuxostat

What is being measured

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

  1. Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint

    The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of this single joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst). Individual erosion scores were summed to a maximum erosion score of 5 for joints in the hands and 10 for joints in the feet. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.

    Measured: Baseline and Month 24

Secondary outcomes (4)

  1. Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs

    Radiographs (X-rays) of 40 joints in the hands and 12 joints in the feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) for a total erosion score range of 0 to 320. Joint space narrowing (JSN) was assessed using a 5-point scale where 0=normal (best) to 4=absence of joint space, presumptive evidence of ankyloses, or complete luxation (worst) for a total JSN score range of 0 to 208. The Erosion Score and the JSN Score were combined for a total possible score of 0 to 528. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.

    Measured: Baseline and Month 24

  2. Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs

    Radiographs (X-rays) of 40 joints in the hands and 12 joints in the feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) for a total erosion score range of 0 to 320. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.

    Measured: Baseline and Month 24

  3. Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint

    The single affected joint was defined as the joint with the history of the first acute gout flare. Magnetic Resonance Imaging (MRI) was evaluated using the Rheumatoid Arthritis MRI Score (RAMRIS). Bone erosion in the proximal and distal location were each assessed in the affected joint using an 11-point scale where 0=no erosion (best) to 10=91-100% bone eroded (worst) for a bone erosion score range of 0 to 20. Bone marrow edema in the proximal and distal location were each assessed using a 4-point scale where 0=no edema (best) to 3=67-100% edema (worst) for a bone marrow edema (BME) score range of 0 to 6. Synovitis was assessed in the affected joint using a 4-point scale where 0=normal (best) to 3=severe (worst). Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.

    Measured: Baseline and Month 24

  4. Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint

    The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of the single affected joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) and Joint space narrowing (JSN) was assessed using a 5-point scale where 0=normal (best) to 4=absence of joint space, presumptive evidence of ankyloses, or complete luxation (worst). The Erosion Score and the JSN Score were summed for the Total Score. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.

    Measured: Baseline and Month 24

Timeline

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

  1. First posted2 Mar 2010 (estimated)
  2. Study startMar 2010
  3. Primary completionSep 2013
  4. Study completionSep 2013

Resources

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
314 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01078389
Sponsor's protocol ID
TMX-67_204
Other IDs
U1111-1113-8098
Status last verified
Sep 2014
First submitted
26 Feb 2010
Last updated
10 Sep 2014
Data monitoring committee
Yes

Publications

  • Dalbeth N, Saag KG, Palmer WE, Choi HK, Hunt B, MacDonald PA, Thienel U, Gunawardhana L. Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study. Arthritis Rheumatol. 2017 Dec;69(12):2386-2395. doi: 10.1002/art.40233.

    PubMed 28975718

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Febuxostat in people with Joint Damage, run by Takeda at 56 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 24 inclusion and 24 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 10 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 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 10 Sep 2014). 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?

Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint (time frame: Baseline and Month 24). 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 NCT01078389, 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 10 Sep 2014.

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