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