AST-120 Used to Treat Mild Hepatic Encephalopathy (ASTUTE)

A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Efficacy, Safety and Tolerability of AST-120 (Spherical Carbon Adsorbent) for 8 Weeks in the Treatment of Mild Hepatic Encephalopathy

The purpose of this study is to determine whether AST-120 is safe and effective in the treatment of mild hepatic encephalopathy.

Study Overview

• Status: Completed
• Conditions: Mild Hepatic Encephalopathy
• Intervention / Treatment: Drug: AST-120

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Fresno, California, United States, 93721
      • UCSF - Fresno Community Regional Medical Center
    • La Jolla, California, United States, 92161
      • UCSD Medical Center
    • San Diego, California, United States, 92037
      • Scripps Clinic
    • San Diego, California, United States, 92101
      • UCSD Medical Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami, Division of Hepatology / Center for Liver Disease
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University, Feinberg School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52246
      • VA Medical Center / University of Iowa Hospital and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners, LLC
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconnes Medical Center, Harvard Medical School
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • Ohio
    • Cincinatti, Ohio, United States, 45267
      • University of Cincinatti
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44109
      • Case Western Reserve / MetroHealth Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center, Division of Hepatology
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of Southern Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75390-9151
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Advanced Liver Therapies, St. Luke's Episcopal Hospital/Baylor College of Medicine
    • Odessa, Texas, United States, 79761
      • Permian Research Foundation
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Center
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire DVAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Confirmed cirrhosis of any cause
2. Abnormal RBANS global summary score
3. Grade 0 or 1 hepatic encephalopathy by West-Haven Scale
4. MELD score < or = 25
5. Females must be postmenopausal, surgically incapable of bearing children or practicing a reliable method of birth control

Exclusion Criteria:

1. Previous participation in any trial involving AST-120
2. History of TIPS or surgically created portocaval shunt
3. Treatment for overt HE within the past 3 months
4. Use of lactulose, rifaximin, neomycin or other antibiotics in the past 7 days
5. Active alcohol abuse
6. Psychosis or organic brain syndromes due to alcohol or other causes
7. Use of interferon and sedating or cognition-altering drugs
8. Undergoing chemotherapy or radiotherapy for the treatment of cancer
9. Active GI bleeding within the past 3 months
10. Presence of an active infection
11. Presence of signs and symptoms of severe dehydration
12. Other major physical or major psychiatric illness within the past 6 months
13. Pregnant, breast feeding, or planning to become pregnant during the study
14. Using hormonal contraception as the only method of birth control

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AST-120 (6g); 2 grams TID	Drug: AST-120; AST-120; Other Names: Spherical carbon adsorbent
Placebo Comparator: Placebo A; 2 grams TID	Drug: AST-120; AST-120; Other Names: Spherical carbon adsorbent
Experimental: AST-120 (12g); 4 grams TID	Drug: AST-120; AST-120; Other Names: Spherical carbon adsorbent
Placebo Comparator: Placebo B; 4 grams TID	Drug: AST-120; AST-120; Other Names: Spherical carbon adsorbent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Neurocognitive improvement, defined as the change in the global summary score of the RBANS at Week 8 compared to Baseline.	8 weeks

Collaborators and Investigators

• Sponsor: Ocera Therapeutics
• Investigators: Study Director: Jeff Bornstein, MD, Ocera Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 20, 2009
• First Posted (Estimate): March 24, 2009

Study Record Updates

• Last Update Posted (Estimate): June 18, 2014
• Last Update Submitted That Met QC Criteria: June 2, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Cognitive impairment; Cirrhosis; Liver Disease; Hepatic encephalopathy; Cognitive dysfunction; HE; Mild hepatic encephalopathy; MHE
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: AST-MHE201