Effect of Febuxostat on Joint Damage in Hyperuricemic Subjects With Early Gout
2014年9月3日 更新者：Takeda
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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
314
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arizona
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Mesa、Arizona、アメリカ
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Tucson、Arizona、アメリカ
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California
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Burbank、California、アメリカ
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Carmichael、California、アメリカ
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Costa Mesa、California、アメリカ
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Irvine、California、アメリカ
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Orange、California、アメリカ
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Rancho Cucamonga、California、アメリカ
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San Diego、California、アメリカ
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San Luis Obispo、California、アメリカ
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Connecticut
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Trumbull、Connecticut、アメリカ
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Florida
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Boynton Beach、Florida、アメリカ
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Daytona Beach、Florida、アメリカ
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Fort Lauderdale、Florida、アメリカ
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Hialeah、Florida、アメリカ
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Miami、Florida、アメリカ
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Sanford、Florida、アメリカ
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Tampa、Florida、アメリカ
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Winter Park、Florida、アメリカ
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Hawaii
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Honolulu、Hawaii、アメリカ
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Illinois
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Arlington Heights、Illinois、アメリカ
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Indiana
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Avon、Indiana、アメリカ
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Greenfield、Indiana、アメリカ
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Kansas
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Wichita、Kansas、アメリカ
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Maine
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Rockport、Maine、アメリカ
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Minnesota
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Chaska、Minnesota、アメリカ
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Mississippi
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Belzoni、Mississippi、アメリカ
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Olive Branch、Mississippi、アメリカ
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Montana
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Billings、Montana、アメリカ
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Missoula、Montana、アメリカ
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Nebraska
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Bellevue、Nebraska、アメリカ
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Nevada
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Henderson、Nevada、アメリカ
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Las Vegas、Nevada、アメリカ
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New Mexico
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Albuquerque、New Mexico、アメリカ
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North Carolina
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Charlotte、North Carolina、アメリカ
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Lenoir、North Carolina、アメリカ
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Shelby、North Carolina、アメリカ
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Ohio
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Dayton、Ohio、アメリカ
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Franklin、Ohio、アメリカ
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Willoughby Hills、Ohio、アメリカ
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ
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Oregon
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Eugene、Oregon、アメリカ
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Pennsylvania
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Duncansville、Pennsylvania、アメリカ
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Rhode Island
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East Providence、Rhode Island、アメリカ
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South Carolina
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Columbia、South Carolina、アメリカ
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South Dakota
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Rapid City、South Dakota、アメリカ
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Tennessee
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Kingsport、Tennessee、アメリカ
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Texas
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Austin、Texas、アメリカ
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Houston、Texas、アメリカ
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San Antonio、Texas、アメリカ
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Southlake、Texas、アメリカ
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Sugar Land、Texas、アメリカ
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Virginia
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Arlington、Virginia、アメリカ
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Burke、Virginia、アメリカ
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Manassas、Virginia、アメリカ
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Wisconsin
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Kenosha、Wisconsin、アメリカ
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- 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*
- 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.
Exclusion Criteria:
- 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.
- 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).
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Febuxostat 40 mg or 80 mg
Febuxostat 40 mg or 80 mg (based on serum urate levels at Day 14), capsules, orally, once daily for up to 24 Months.
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フェブキソスタットカプセル
他の名前：
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プラセボコンパレーター：Placebo
Febuxostat placebo-matching capsules, orally, once daily for up to 24 Months.
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Febuxostat placebo-matching capsules
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint
時間枠：Baseline and Month 24
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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.
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Baseline and Month 24
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs
時間枠：Baseline and Month 24
|
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.
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Baseline and Month 24
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Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs
時間枠：Baseline and Month 24
|
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.
|
Baseline and Month 24
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Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint
時間枠：Baseline and Month 24
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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.
|
Baseline and Month 24
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Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint
時間枠：Baseline and Month 24
|
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.
|
Baseline and Month 24
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
便利なリンク
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2010年3月1日
一次修了 (実際)
2013年9月1日
研究の完了 (実際)
2013年9月1日
試験登録日
最初に提出
2010年2月26日
QC基準を満たした最初の提出物
2010年3月1日
最初の投稿 (見積もり)
2010年3月2日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年9月10日
QC基準を満たした最後の更新が送信されました
2014年9月3日
最終確認日
2014年9月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。