Study to Assess the Safety, Tolerability, and Pharmacodynamics of RTA 402 in Patients With Hepatic Dysfunction

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

This study assesses the safety and tolerability of RTA 402 in patients with liver disease.

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.