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

Ocera Therapeutics

Status and phase

Completed

Phase 2

Conditions

Hepatic Encephalopathy

Treatments

Drug: AST-120

Drug: lactulose

Study type

Interventional

Funder types

Industry

Identifiers

NCT00558038

AST015

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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