A Phase 3 Randomized, Double-Blind, Multicenter, Placebo-Controlled, Combination Study to Evaluate the Efficacy and Safety of Lesinurad and Allopurinol Compared to Allopurinol Alone in Subjects With Gout Who Have Had an Inadequate Hypouricemic Response to Standard of Care Allopurinol.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 607
- 主要终点
- Proportion of Subjects With an sUA Level That is < 6.0 mg/dL
研究概览
简要总结
This study that compare the serum uric acid lowering effects, clinical benefits, and safety of lesinurad in combination with allopurinol to allopurinol alone in subjects with gout who have had an inadequate response to allopurinol.
详细描述
Allopurinol is the standard of care for the treatment of gout. Nevertheless, most patients treated with allopurinol do not achieve the recommended serum urate (sUA) target of < 6.0 mg/dL and need additional therapy to achieve the target. Probenecid and benzbromarone are uric acid transporter 1 (URAT1) inhibitors, generally recommended as second-line agents for patients who are either resistant to or intolerant of allopurinol. However, benzbromarone is not available in the US and probenecid is rarely used. Consequently, there is a clear unmet medical need for a new safe and effective therapy for gout, such as lesinurad, a potent URAT1 inhibitor, that can be used in combination with allopurinol in patients not responding adequately to allopurinol monotherapy so that very high rates of response can be achieved by nearly all gout patients, rather than a minority.The subjects selected for this study will have moderate to severe gout with an inadequate response to allopurinol
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
- Double (Participant, Care Provider)
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 meets the diagnosis of gout as per the American Rheumatism Association Criteria for the Classification of Acute Arthritis of Primary Gout.
- •Subject has been taking allopurinol as the sole urate-lowering therapy indicated for the treatment of gout for at least 8 weeks prior to the Screening Visit at a stable, medically appropriate dose, as determined by the investigator, of at least 300 mg per day (at least 200 mg for subjects with moderate renal impairment).
- •Subject must be able to take gout flare prophylaxis with colchicine or an Nonsteroidal anti-inflammatory drug (NSAID) (including Cox-2 selective NSAID) ± PPI.
- •Subject has an sUA level ≥ 6.5 mg/dL at the Screening Visit and ≥ 6.0 mg/dL at Day -7 Visit.
- •Subject has reported at least 2 gout flares in the prior 12 months.
- •Body mass index (BMI) < 45 kg/m2
排除标准
- •Subject with known hypersensitivity or allergy to allopurinol.
- •Subject who is taking any other approved urate-lowering medication that is indicated for the treatment of gout other than allopurinol within 8 weeks of the Screening Visit.
- •Subject who is pregnant or breastfeeding.
- •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 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 class III or IV heart failure, myocardial infarction, stroke, or deep venous thrombosis; or subjects currently receiving anticoagulants.
- •Subject with uncontrolled hypertension.
- •Subject with an estimated creatinine clearance < 30 mL/min.
- •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 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 200 mg + allopurinol
干预措施: Allopurinol (Drug)
lesinurad 400 mg + allopurinol
干预措施: Lesinurad (Drug)
lesinurad 400 mg + allopurinol
干预措施: Allopurinol (Drug)
Placebo + allopurinol
干预措施: Placebo (Drug)
lesinurad 200 mg + allopurinol
干预措施: Lesinurad (Drug)
Placebo + allopurinol
干预措施: Allopurinol (Drug)
结局指标
主要结局
Proportion of Subjects With an sUA Level That is < 6.0 mg/dL
时间窗: 6 Months, analysis after all subjects complete 12 months
次要结局
- Gout Flares(12 Months)
- Tophus(12 Months)