Safety and Efficacy of AST-120 Compared to Lactulose in Patients With Hepatic Encephalopathy - Full Text View

Sponsor:	Ocera Therapeutics
Information provided by:	Ocera Therapeutics
ClinicalTrials.gov Identifier:	NCT00558038

Purpose

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.

Condition	Intervention	Phase
Hepatic Encephalopathy	Drug: AST-120 Drug: lactulose	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Comparison of Different Treatment Regimens in Patients With Stage 1-2 Type C Hepatic Encephalopathy: AST-120 vs Lactulose

Resource links provided by NLM:

Drug Information available for: Lactulose

U.S. FDA Resources

Further study details as provided by Ocera Therapeutics:

Primary Outcome Measures:

Change in Westhaven Scale [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Efficacy: Change in Hepatic Encephalopathy Scoring Algorithm (HESA) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Efficacy: Reduction of venous ammonia levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Efficacy: Serum bile acids and amino acid profile [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Efficacy: Reduction in itching (visual analog scale) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Efficacy: Presence or absence of asterixis [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Safety: Clinical laboratory tests [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate, body temperature) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	September 2007
Estimated Study Completion Date:	June 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator	Drug: lactulose lactulose
2: Experimental	Drug: AST-120 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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558038

Locations

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

Sponsors and Collaborators

Ocera Therapeutics

Investigators

Principal Investigator:

Paul Pockros, MD

Scripps Clinic

More Information

No publications provided

Responsible Party:	Ocera Therapeutics, Inc. ( Scott Harris, MD / Chief Medical Officer )
Study ID Numbers:	AST015
Study First Received:	November 9, 2007
Last Updated:	March 19, 2009
ClinicalTrials.gov Identifier:	NCT00558038 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ocera Therapeutics:

Hepatic
Encephalopathy
Liver
Liver Disease

Liver Failure
Lactulose
AST-120

Additional relevant MeSH terms:

Liver Diseases
Neurotoxicity Syndromes
Brain Damage, Chronic
Disorders of Environmental Origin
Central Nervous System Viral Diseases
Brain Diseases
Signs and Symptoms
Mental Disorders
Therapeutic Uses
Neurobehavioral Manifestations
Lactulose
Hepatic Insufficiency
Delirium
Liver Failure
Metabolic Diseases

Nervous System Diseases
Gastrointestinal Agents
Poisoning
Central Nervous System Diseases
Confusion
Pharmacologic Actions
Encephalitis
Virus Diseases
Hepatic Encephalopathy
Digestive System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Central Nervous System Infections
Neurologic Manifestations
Brain Diseases, Metabolic

ClinicalTrials.gov processed this record on November 25, 2009