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.

Study Overview

• Status: Terminated
• Conditions: Liver Disease
• Intervention / Treatment: Drug: RTA 402; Drug: RTA 402; Drug: RTA 402

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.

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; RTA 402	Drug: RTA 402; 5 mg oral capsules; Drug: RTA 402; 25 mg oral capsules; Drug: RTA 402; 50 mg oral capsules
Experimental: 2; RTA 402	Drug: RTA 402; 5 mg oral capsules; Drug: RTA 402; 25 mg oral capsules; Drug: RTA 402; 50 mg oral capsules
Experimental: 3; RTA 402	Drug: RTA 402; 5 mg oral capsules; Drug: RTA 402; 25 mg oral capsules; Drug: RTA 402; 50 mg oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety and tolerability of multiple-dose oral administration of RTA 402 in patients with hepatic dysfunction.	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To correlate the biological activity of RTA 402 with drug concentration in plasma.	28 days

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Investigators: Principal Investigator: Thomas C. Marbury, MD, Orlando Clinical Research Center

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2007
• Primary Completion (Actual): November 30, 2007
• Study Completion (Actual): November 30, 2007

Study Registration Dates

• First Submitted: October 26, 2007
• First Submitted That Met QC Criteria: October 26, 2007
• First Posted (Estimated): October 30, 2007

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: RTA 402-C-0701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/