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

Primary Purpose

Hepatic Encephalopathy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AST-120
lactulose
Sponsored by
Ocera Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Encephalopathy focused on measuring Hepatic, Encephalopathy, Liver, Liver Disease, Liver Failure, Lactulose, AST-120

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Alabama
  • Cedars Sinai Medical Center
  • Scripps Clinic
  • Veterans Medical Center San Diego
  • Washington Hospital Center - MedStar Research Institute
  • Digestive Healthcare of Georgia
  • University of Chicago
  • Tulane University Health Sciences Center
  • University of Massachusetts Medical School
  • Weill Medical College of Cornell
  • Mount Sinai School of Medicine
  • Cleveland Clinic Foundation
  • Baylor University Medical Center
  • Baylor University Medical Center
  • St. Luke's Advanced Liver Therapies / St. Luke's Texas Liver Coalition - Baylor College of Medicine
  • Metropolitan Research
  • McGuire VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

Change in Westhaven Scale

Secondary Outcome Measures

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)

Full Information

First Posted
November 9, 2007
Last Updated
May 27, 2014
Sponsor
Ocera Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00558038
Brief Title
Safety and Efficacy of AST-120 Compared to Lactulose in Patients With Hepatic Encephalopathy
Acronym
AST015
Official Title
Comparison of Different Treatment Regimens in Patients With Stage 1-2 Type C Hepatic Encephalopathy: AST-120 vs Lactulose
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ocera Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Encephalopathy
Keywords
Hepatic, Encephalopathy, Liver, Liver Disease, Liver Failure, Lactulose, AST-120

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AST-120
Intervention Description
AST-120
Intervention Type
Drug
Intervention Name(s)
lactulose
Other Intervention Name(s)
Chronulac, Constilac, Constulose, Duphalac, Evalose
Intervention Description
lactulose
Primary Outcome Measure Information:
Title
Change in Westhaven Scale
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Efficacy: Change in Hepatic Encephalopathy Scoring Algorithm (HESA)
Time Frame
4 weeks
Title
Efficacy: Reduction of venous ammonia levels
Time Frame
4 weeks
Title
Efficacy: Serum bile acids and amino acid profile
Time Frame
4 weeks
Title
Efficacy: Reduction in itching (visual analog scale)
Time Frame
4 weeks
Title
Efficacy: Presence or absence of asterixis
Time Frame
4 weeks
Title
Safety: Clinical laboratory tests
Time Frame
4 weeks
Title
Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate, body temperature)
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Pockros, MD
Organizational Affiliation
Scripps Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Cedars Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Scripps Clinic
City
San Diego
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Veterans Medical Center San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
Washington Hospital Center - MedStar Research Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Digestive Healthcare of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worchester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Weill Medical College of Cornell
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Baylor University Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
St. Luke's Advanced Liver Therapies / St. Luke's Texas Liver Coalition - Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Metropolitan Research
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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