Randomized, Double-blind, Placebo-controlled, Multiple-dose, Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacodynamics of RTA 402 (CDDO-Me) Administered Orally for 14 Days in Patients With Hepatic Dysfunction
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of multiple-dose oral administration of RTA 402 in patients with hepatic dysfunction.
研究概览
简要总结
This study assesses the safety and tolerability of RTA 402 in patients with liver disease.
详细描述
RTA 402 is a synthetic triterpenoid that is designed to suppress oxidative stress and inflammatory processes that play a significant role in a wide variety of diseases. It is a potent suppressor of inflammation and oxidative stress. Oxidative stress plays a role in the pathogenesis of hepatitis, and RTA 402 has demonstrated activity in a preclinical model of hepatitis, in addition to other models of inflammation.
This is a 28-day, multiple-dose, dose-escalation study. It is anticipated that a total of 3 groups of 8 patients each will be enrolled, in which 6 patients in each group will be randomized to receive RTA 402, and 2 patients per group will be randomized to placebo (3:1). Patients will receive treatment daily for 14 days with a starting dose of 5mg, 25mg, or 50mg. Patients will return for follow up visits on Days 16 and 21, and complete end of study procedures on Day 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Chronic liver disease.
- •An estimated creatinine clearance of ≥ 60 mL/min.
- •Serum alanine transaminase (ALT) or aspartate transaminase (AST) elevation must be above the upper limit of normal and below 5 times the upper limit of normal for patients with underlying liver disease; Child-Pugh score 5 to 9 (mild to moderate impairment).
- •Patient must agree to practice effective contraception during the entire study period.
- •Patient is willing to avoid strenuous physical activity from 24 hours prior to the study start, throughout the study, and for 2 weeks after the administration of the dose of study drug
- •Patient is willing to avoid any alcohol consumption for the 24 hours prior to, and the 48 hours after administration of study drug; and avoid excessive alcohol consumption for the duration of the follow-up period.
- •Patient must be able and willing to sign informed consent form.
排除标准
- •Patient with clinically significant illnesses or recent hospitalization (within 60 days) which could compromise participation in the study in the judgment of the investigator, including: uncontrolled diabetes; active or uncontrolled infection; Confirmed diagnosis of HIV infection; uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
- •Patient with any other auto immune disease, major chronic inflammatory disease or syndrome requiring significant treatment within the past year.
- •Patients who are pregnant or breast feeding
- •Patient receiving or has received any investigational drug within 30 days prior (or is currently using an investigational device)
- •Patients with prior (within 4 weeks) or concurrent treatment with oral steroids, or protein-based therapy (i.e. TNFa)
- •Patients with positive urine screen for drugs of abuse except when receiving a prescribed medication for a known indication
- •Patients with Grade 2 or above hepatic encephalopathy.
- •Patients who donated blood or experienced a significant blood loss (>450 mL) within 8 weeks of screening
- •Patients with a history of bleeding varices within 12 weeks of screening.
- •Patients with psychiatric illness or other condition that would limit compliance with study requirements.
研究组 & 干预措施
1
RTA 402
干预措施: RTA 402 (Drug)
2
RTA 402
干预措施: RTA 402 (Drug)
3
RTA 402
干预措施: RTA 402 (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of multiple-dose oral administration of RTA 402 in patients with hepatic dysfunction.
时间窗: 28 days
次要结局
- To correlate the biological activity of RTA 402 with drug concentration in plasma.(28 days)