Clinical trial NCT00550849: Study to Assess the Safety, Tolerability, and Pharmacodynamics of RTA 402 in Patients With Hepatic Dysfunction
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Liver Disease
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-10-30
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the safety and tolerability of multiple-dose oral administration of RTA 402 in patients with hepatic dysfunction.
timeFrame: 28 days
Secondary outcomes:
measure: To correlate the biological activity of RTA 402 with drug concentration in plasma.
timeFrame: 28 days
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Orlando Clinical Research Center
name: Thomas C. Marbury, MD
role: PRINCIPAL_INVESTIGATOR
References: