A Phase 2, Randomized, Double Blind, Multicenter, Placebo Controlled Study to Evaluate the Efficacy and Safety of Febuxostat 40 mg XR, 80 mg XR, 40 mg IR and 80 mg IR in Subjects With Gout and Moderate Renal Impairment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 189
- 试验地点
- 11
- 主要终点
- Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of febuxostat 40 mg extended release (XR) and 80 mg XR in comparison with febuxostat 40 mg immediate release (IR) and 80 mg IR, respectively, in gout participants with moderate renal impairment.
详细描述
The drug being tested in this study is called febuxostat. Febuxostat is being tested to decrease and maintain serum urate in people who have gout with moderate renal impairment. This study will look at serum urate levels in people who take febuxostat extended release (XR) capsules compared to febuxostat immediate release (IR) capsules and placebo.
The study will enroll approximately 200 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- Febuxostat 40 mg XR
- Febuxostat 80 mg XR
- Febuxostat 40 mg IR
- Febuxostat 80 mg IR
- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.
All participants will be asked to take one capsule at the same time each day throughout the study, and will be asked to call an interactive voice response system any time they are having a gout flare up. In addition to study medication, participants will also take 0.6 mg of colchicine every other day or naproxen 250 mg twice a day with lansoprazole 15 mg once a day to prevent gout flare ups.
This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to approximately 4 months and participants will make up to 7 visits to the clinic.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
- •The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure.
- •Has a history or presence of gout defined as having one or more of the American Rheumatism Association (ARA) 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:
- •i. more than one attack of acute arthritis, ii. maximum inflammation developed within 1 day, iii. monoarticular arthritis, iv. redness observed over joints, v. first metatarsophalangeal joint painful or swollen, vi. unilateral first metatarsophalangeal joint attack, vii. unilateral tarsal joint attack, viii. tophus (proven or suspected), ix. Hyperuricemia, x. asymmetric swelling within a joint on x-ray, xi. subcortical cysts without erosions on x-ray, xii. joint fluid culture negative for organisms during attack.
- •Is male or female at least 18 years of age, inclusive.
- •A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
- •Have a serum urate (sUA) level ≥8.0 mg/dL at the Day -4 Visit or at the retest visit.
- •Has an estimated Glomerular Filtration Rate (eGRF) [Modification of Diet in Renal Disease (MDRD)] ≥30 mL/min and <60 mL/min at Screening visit (Day -21 for participants on urate lowering therapy (ULT) and Day -4 for participants not on ULT) or at the retest visit.
- •Has at least one gout flare within 12 months prior to Screening visit.
排除标准
- •Has received any investigational compound within 30 days prior to Screening.
- •Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
- •Is breastfeeding or pregnant.
- •Has secondary hyperuricemia (eg, due to myeloproliferative disorder).
- •Has a history of xanthinuria.
- •Has received ULT (ie, allopurinol, probenecid, etc.) within 20 days prior to Day 1/Randomization Visit.
- •Has a known hypersensitivity to febuxostat or any components of their formulation; has a known hypersensitivity to naproxen, any other nonsteroidal anti-inflammatory drug (NSAID), aspirin, lansoprazole, colchicine or any components in their formulation.
- •Has active peptic ulcer disease.
- •Has a history of cancer (other than basal cell carcinoma of the skin) within 5 years prior to the Screening Visit.
- •Has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values >2 x the upper limit of normal (ULN).
- •Has rheumatoid arthritis which requires treatment.
- •Has a significant medical condition and/or conditions that would interfere with the treatment, safety, or compliance with the protocol.
- •Has experienced either a myocardial infarction (MI), stroke, hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure or hospitalized transient ischemic attack (TIA).
- •Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the Screening visit. Participant consumes >14 alcoholic beverages/week.
- •Has participated in another investigational study within the 30 days prior to the Screening Visit.
- •Has a known history of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
- •Is required to take excluded medications.
研究组 & 干预措施
Febuxostat IR 40 mg
Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Febuxostat IR (Drug)
Febuxostat IR 40 mg
Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Colchicine (Drug)
Febuxostat IR 40 mg
Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Naproxen (Drug)
Febuxostat IR 40 mg
Febuxostat Immediate Release (IR) 40 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Lansoprazole (Drug)
Febuxostat IR 80 mg
Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Febuxostat IR (Drug)
Febuxostat IR 80 mg
Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Colchicine (Drug)
Placebo
Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Febuxostat placebo (Drug)
Febuxostat IR 80 mg
Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Naproxen (Drug)
Febuxostat IR 80 mg
Febuxostat IR 80 mg over-encapsulated tablet, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Lansoprazole (Drug)
Febuxostat XR 40 mg
Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Febuxostat XR (Drug)
Febuxostat XR 40 mg
Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Colchicine (Drug)
Febuxostat XR 40 mg
Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Naproxen (Drug)
Febuxostat XR 40 mg
Febuxostat Extended Release (XR) 40 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Lansoprazole (Drug)
Febuxostat XR 80 mg
Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Febuxostat XR (Drug)
Febuxostat XR 80 mg
Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Colchicine (Drug)
Febuxostat XR 80 mg
Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Naproxen (Drug)
Febuxostat XR 80 mg
Febuxostat XR 80 mg over-encapsulated capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Lansoprazole (Drug)
Placebo
Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Colchicine (Drug)
Placebo
Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Naproxen (Drug)
Placebo
Febuxostat placebo-matching capsule, orally, once daily, and colchicine 0.6 mg tablet, orally, every other day, or, naproxen 250 mg tablets, orally, twice a day and lansoprazole 15 mg capsule, orally once daily, for 3 months.
干预措施: Lansoprazole (Drug)
结局指标
主要结局
Percentage of Participants With Serum Urate <5.0 mg/dL at Month 3
时间窗: Month 3
次要结局
- Percentage of Participants With Serum Urate <6.0 mg/dL at Month 3(Month 3)
- Percentage of Participants With at Least One Gout Flare Requiring Treatment(Baseline to Month 3)