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

Hepatic Encephalopathy Clinical Trial

— AST015  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558038
• Other study ID #: AST015
• Status: Completed
• Phase: Phase 2
• First received: November 9, 2007
• Last updated: May 27, 2014
• Start date: September 2007
• Est. completion date: June 2009

Study information

• Verified date: May 2014
• Source: Ocera Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

Drug:
• AST-120
AST-120
• lactulose
lactulose

Locations

Country	Name	City	State
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Metropolitan Research	Fairfax	Virginia
United States	Baylor University Medical Center	Houston	Texas
United States	St. Luke's Advanced Liver Therapies / St. Luke's Texas Liver Coalition - Baylor College of Medicine	Houston	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	Weill Medical College of Cornell	New York	New York
United States	McGuire VA Medical Center	Richmond	Virginia
United States	Scripps Clinic	San Diego	California
United States	Veterans Medical Center San Diego	San Diego	California
United States	Washington Hospital Center - MedStar Research Institute	Washington	District of Columbia
United States	University of Massachusetts Medical School	Worchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Ocera Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Westhaven Scale		4 weeks	No
Secondary	Efficacy: Change in Hepatic Encephalopathy Scoring Algorithm (HESA)		4 weeks	No
Secondary	Efficacy: Reduction of venous ammonia levels		4 weeks	No
Secondary	Efficacy: Serum bile acids and amino acid profile		4 weeks	No
Secondary	Efficacy: Reduction in itching (visual analog scale)		4 weeks	No
Secondary	Efficacy: Presence or absence of asterixis		4 weeks	No
Secondary	Safety: Clinical laboratory tests		4 weeks	No
Secondary	Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate, body temperature)		4 weeks	No