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

Condition(s) targeted: Hepatic Encephalopathy

Intervention: AST-120 (Drug); lactulose (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Ocera Therapeutics

Official(s) and/or principal investigator(s):
Paul Pockros, MD, Principal Investigator, Affiliation: Scripps Clinic

Overall contact:
Michelle Resler, Phone: 858-436-3916, Email: mresler@ocerainc.com

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.

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

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change in Westhaven Scale

Secondary outcome:

Efficacy: Change in Hepatic Encephalopathy Scoring Algorithm (HESA)

Efficacy: Reduction of venous ammonia levels

Efficacy: Serum bile acids and amino acid profile

Efficacy: Reduction in itching (visual analog scale)

Efficacy: Presence or absence of asterixis

Safety: Clinical laboratory tests

Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate, body temperature)

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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

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

Michelle Resler, Phone: 858-436-3916, Email: mresler@ocerainc.com

University of Alabama, Birmingham, Alabama 35294, United States; Recruiting
Cynthia Joiner, RN
Brendan McGuire, MD, Principal Investigator

Scripps Clinic, San Diego, California 92037, United States; Recruiting
Christi Bonslaver, RN
Donald Hillebrand, MD, Principal Investigator

Veterans Medical Center San Diego, San Diego, California 92161, United States; Recruiting
Lori Barry
Julia Hall
Mario Chojkier, MD, Principal Investigator

Cedars Sinai Medical Center, Los Angeles, California 90048, United States; Recruiting
Teresa DiDiego
Fred Poordad, MD, Principal Investigator

Washington Hospital Center - MedStar Research Institute, Washington, District of Columbia 20010, United States; Recruiting
Michelle Mendoza, MD
Averell Sherker, MD, Principal Investigator

Digestive Healthcare of Georgia, Atlanta, Georgia 30309, United States; Recruiting
Julie Costello, CRC
Raymond Rubin, MD, Principal Investigator

University of Chicago, Chicago, Illinois 60637, United States; Recruiting
Katie Wherity, RN
Gautham Reddy, MD, Principal Investigator

Tulane University Health Sciences Center, New Orleans, Louisiana 70112, United States; Recruiting
Joni Murray
Luis Balart, MD, Principal Investigator

University of Massachusetts Medical School, Worchester, Massachusetts 01655, United States; Recruiting
Donna Giansiracusa, RN
Graham Barnard, MD, Principal Investigator

Weill Medical College of Cornell, New York, New York 10021, United States; Recruiting
Jennifer Byrnes, RN
Sam Sigal, MD, Principal Investigator

Mount Sinai School of Medicine, New York, New York 10029, United States; Recruiting
Aniceto Javaluyas
Priya Grewal, MD, Principal Investigator

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Paula Freeman-Vida, RN
Paul Tokar, RN
Robert O'Shea, MD, Principal Investigator

Baylor University Medical Center, Dallas, Texas 75246, United States; Recruiting
Sonnya Coultrup, RN
Jacqueline O'Leary, MD, Principal Investigator

St. Luke's Advanced Liver Therapies / St. Luke's Texas Liver Coalition - Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Gerard Brown, RN
John Vierling, MD, Principal Investigator

Baylor University Medical Center, Houston, Texas 77030, United States; Recruiting
Kethy Gasitashvili
Boris Yoffe, MD, Principal Investigator

McGuire VA Medical Center, Richmond, Virginia 23249, United States; Recruiting
Edith Gavis, RN
Douglas Heuman, MD, Principal Investigator

Metropolitan Research, Fairfax, Virginia 22031, United States; Recruiting
Arman Kashani, MD
Vinod Rustgi, MD, Principal Investigator

Starting date: September 2007
Ending date: December 2008
Last updated: June 13, 2008