A Phase 3 Randomized, Double-Blind, Multicenter, Placebo- Controlled, Combination Study to Evaluate the Efficacy and Safety of Lesinurad and Febuxostat Compared to Febuxostat Alone at Lowering Serum Uric Acid and Resolving Tophi in Subjects With Tophaceous Gout
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 330
- 主要终点
- Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6
研究概览
简要总结
This study will compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with febuxostat to febuxostat alone in patients with tophaceaous gout.
详细描述
Febuxostat is an XO (Xanthine Oxidase) Inhibitor approved Urate Lowering Therapy (ULT) for patients with gout. Although febuxostat has been demonstrated to be superior to allopurinol in lowering serum urate (sUA) to < 6mg/dL in 3 randomized, controlled clinical trials, proportions of subjects experiencing a reduction in tophus area and gout flares were not significantly different compared to allopurinol. Although this study will allow subjects who are naïve to ULT to enroll, it is anticipated that the majority of subjects will currently be taking or have previously experienced XO Inhibitor therapy. This trial will enroll a population of subjects with high uric acid body burden, as all must demonstrate the presence of tophi.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is able to understand the study procedures, the risks involved and willing to provide written informed consent before the first study related activity.
- •Subject is willing to adhere to the visit/protocol schedules.
- •Subject meets the diagnosis of gout as per the American Rheumatism Association
- •Criteria for the Classification of Acute Arthritis of Primary Gout.
- •Subject meets one of the following criteria:
- •Subjects who are not currently taking an approved ULT must have an sUA value of ≥ 8 mg/dL (476 µmol/L).
- •Subjects entering the study on a medically appropriate dose of febuxostat or allopurinol must have an sUA value of ≥ 6.0 mg/dL (357 µmol/L).
- •Subject must be able to take gout flare prophylaxis with colchicine or non-steroidal anti-inflammatory drug (NSAID) (including Cox-2 selective NSAID) ± PPI.
- •Subject with at least 1 measurable tophus on the hands/wrists and/or feet/ankles ≥ 5 mm and ≤ 20 mm in the longest diameter.
- •Body mass index (BMI) < 45 kg/m2
排除标准
- •Subject with known hypersensitivity or allergy to febuxostat.
- •Subject who is taking any approved urate-lowering medication other than allopurinol or febuxostat that is indicated for the treatment of gout within 8 weeks of the Screening Visit.
- •Subject who previously received pegloticase.
- •Subject who consumes more than 14 drinks of alcohol per week (eg, 1 drink = 5 oz [150 mL] of wine, 12 oz [360 mL] of beer, or 1.5 oz [45 mL] of hard liquor).
- •Subject with a history or suspicion of drug abuse within the past 5 years.
- •Subject with a history of myositis/myopathy or rhabdomyolysis.
- •Subject that requires or may require systemic immunosuppressive or immunomodulatory treatment.
- •Subject with known or suspected human immunodeficiency virus (HIV) infection.
- •Subject with a positive test for active hepatitis B or hepatitis C infection.
- •Subject with a history of malignancy within the previous 5 years with the exception of non-melanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia or treated in situ Grade 1 cervical cancer.
- •Subject within the last 12 months with: unstable angina, New York Heart Association thrombosis; or subjects currently receiving anticoagulants.
- •Subject with uncontrolled hypertension.
- •Subject with an estimated creatinine clearance < 30 mL/min.
- •Subjects with a creatine kinase > 2.5 x ULN at any time during the Screening Period.
- •Subject with active peptic ulcer disease requiring treatment.
- •Subject with a history of xanthinuria, active liver disease, or hepatic dysfunction.
- •Subject receiving chronic treatment with more than 325 mg of salicylates per day.
- •Subject taking valpromide, progabide, or valproic acid.
- •Subject who has received an investigational therapy within 8 weeks or 5 half-lives (whichever is longer) prior to the Screening Visit.
- •Subject with any other medical or psychological condition, which in the opinion of the Investigator and/or Medical Monitor, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study.
研究组 & 干预措施
lesinurad 400 mg + febuxostat 80 mg
干预措施: Lesinurad (Drug)
lesinurad 400 mg + febuxostat 80 mg
干预措施: Febuxostat (Drug)
lesinurad 200 mg + febuxostat 80 mg
干预措施: Lesinurad (Drug)
lesinurad 200 mg + febuxostat 80 mg
干预措施: Febuxostat (Drug)
placebo + febuxostat 80 mg
干预措施: Placebo (Drug)
placebo + febuxostat 80 mg
干预措施: Febuxostat (Drug)
结局指标
主要结局
Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6
时间窗: 6 months, analysis after all subjects complete 12 months
Proportion of subjects with an sUA level that is \< 5.0 mg/dL by Month 6
次要结局
- Complete Resolution of at Least One Target Tophus(12 Months)
- Complete or Partial Response of at Least One Tophus(12 Months)
- Quality of Life(12 Months)