Safety and Efficacy of AST-120 Compared to Lactulose in Patients With Hepatic Encephalopathy (AST015)

Comparison of Different Treatment Regimens in Patients With Stage 1-2 Type C Hepatic Encephalopathy: AST-120 vs Lactulose

The purpose of this study is to evaluate the safety and effectiveness of the experimental drug AST-120 compared to lactulose in patients with mild hepatic encephalopathy.

Study Overview

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

Detailed Description

This is a multi-center, open-label, four week trial comparing AST-120 to lactulose in patients with mild (Stage 1-2) hepatic encephalopathy.

Patients will be randomized into two groups:

• Lactulose
• AST-120

Patients meeting the inclusion criteria will take either AST-120 or lactulose for 4 weeks (28 days). AST-120 will be distributed in 2 gram sachets to be taken four times daily. Lactulose will be taken in the same formulation, at the same dose and frequency as previously prescribed for the individual patient.

Lactulose naïve patients who are randomized to lactulose will receive an initial dose of 30cc twice a day. The dose should be titrated at the discretion of the investigator until the patient is experiencing 2-3 soft stools per day.

Patients randomized to AST-120 will receive 2 grams four times a day for the duration of the study. Titration of AST-120 will NOT be allowed.

Patients will be evaluated throughout the study for efficacy and safety. A follow-up visit will be scheduled 1 week after the end of the 4 week treatment period.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University Of Alabama
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • San Diego, California, United States, 92037
      • Scripps Clinic
    • San Diego, California, United States, 92161
      • Veterans Medical Center San Diego
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center - MedStar Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Massachusetts
    • Worchester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • St. Luke's Advanced Liver Therapies / St. Luke's Texas Liver Coalition - Baylor College of Medicine
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Research
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with End Stage Liver Disease secondary to any cause (patients who have undergone portosystemic shunting (TIPS) procedure > 3 months prior to randomization can be included)
• Lactulose naïve patients or patients currently on an established dose of lactulose
• MELD score ≤ 15 (MELD score up to 20 is allowable if it has remained stable for at least 3 months)
• Meet the criteria for Stage 1-2 hepatic encephalopathy according to the Westhaven Scale
• Patients must have discontinued rifaximin or other oral antibiotics for at least 48 hours prior to randomization
• Able and willing to comply with all protocol procedures for the planned duration of the study
• Able and willing to understand, sign and date an informed consent document, and authorize access to protected health information
• Have a person (spouse, relative, or friend) willing to accompany the patient to the study visits (patients in this condition are not recommended to drive a vehicle)
• Females must be postmenopausal, surgically incapable of bearing children, or practicing a reliable method of birth control (intrauterine devices, spermicide and barrier). Partner/spouse sterility may also qualify at the investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline.

Note: Patients already on lactulose and randomized to AST-120 will stop taking lactulose on the day they begin taking AST-120.

Exclusion Criteria:

• Patients whose condition necessitates continuous administration of antibiotics (e.g. rifaximin, neomycin, metronidazole)
• Patients undergoing chemotherapy for treatment of cancer (patients with hepatocellular carcinoma being treated by methods other than chemotherapy may be enrolled)
• Patients who require continued treatment with narcotics or sedatives
• Patients who have active GI bleeding
• Patients who have an active infection
• Patients who have signs and symptoms of severe dehydration
• Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling
• Unable to attend all visits required by the protocol
• Female patients must be EXCLUDED if they are pregnant, breast feeding, planning to become pregnant during the study or using hormonal contraception as their only method of birth control

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Drug: AST-120; AST-120
Active Comparator: 1	Drug: lactulose; lactulose; Other Names: Chronulac, Constilac, Constulose, Duphalac, Evalose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Westhaven Scale	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy: Change in Hepatic Encephalopathy Scoring Algorithm (HESA)	4 weeks
Efficacy: Reduction of venous ammonia levels	4 weeks
Efficacy: Serum bile acids and amino acid profile	4 weeks
Efficacy: Reduction in itching (visual analog scale)	4 weeks
Efficacy: Presence or absence of asterixis	4 weeks
Safety: Clinical laboratory tests	4 weeks
Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate, body temperature)	4 weeks

Collaborators and Investigators

• Sponsor: Ocera Therapeutics
• Investigators: Principal Investigator: Paul Pockros, MD, Scripps Clinic

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: November 9, 2007
• First Submitted That Met QC Criteria: November 9, 2007
• First Posted (Estimate): November 14, 2007

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 27, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Liver Disease; Hepatic; Liver; Encephalopathy; Liver Failure; AST-120; Lactulose
• 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; Gastrointestinal Agents; Lactulose
• Other Study ID Numbers: AST015