The Role of Bacterial Overgrowth and Delayed Intestinal Transit in Hepatic Encephalopathy

• Status: Unknown status
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The study will be conducted in two phases. Phase A will evaluate the contribution of bacterial overgrowth and colonic inertia to development of Hepatic Encephalopathy (HE)in 50 ambulatory subjects with HE and hepatitis C cirrhosis. This phase will include a Screening and Evaluation Visit.

Phase B will evaluate the effect of rifaximin on bacterial outgrowth and severity of HE in 20 of the subjects enrolled in Phase A who have a somewhat greater degree of encephalopathy.

The purpose of this study is to evaluate the following:

1. the relationship between bacterial overgrowth and the presence and severity of HE in patients with hepatitis C cirrhosis;

2. the effectiveness and tolerability of rifaximin relative to placebo in treatment of HE associated with hepatitis C cirrhosis;

3. the relationship between bacterial overgrowth and the presence and severity of HE before and after rifaximin treatment.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Collaborators: Bausch Health Americas, Inc.; Valeant Pharmaceuticals International, Inc.
• Treatments: Rifaximin

Criteria

Phase A Inclusion Criteria:

• Subject is 18 to 70 years of age, inclusive.

• Subject has cirrhosis due to chronic HCV infection as documented by:

• Subject has evidence of hepatic encephalopathy as evidenced by:

• Neuro-psychometric Testing (Number Connection Test, Trails Test, etc.)

• Subject is non-azotemic (creatinine <1.5mg/dL) and ambulatory at screening.

• Subject has cirrhosis due to chronic HCV as documented by: pathologic or clinical and radiographic evidence of cirrhosis with a positive HCV RNA PCR level.

Phase A Exclusion Criteria:

• Subject has received active interferon therapy within 2 weeks of enrollment.

• Subject is pregnant or lactating.

• Subject has a life expectancy of less than 100 days.

• Subject has a history of alcohol abuse within 6 months of enrollment.

• Subject has active gastrointestinal bleeding at time of enrollment.

• Subject has used an agent that alters intestinal motility, eg, methadone, cholestyramine, tricyclic antidepressants.

• Subject is unable to take oral medication.

• Subject has used neomycin or other antibiotic within 2 weeks of enrollment or is actively using lactulose at time of enrollment.

• Subject is taking or has hypersensitivity or allergy to rifaximin or rifampin.

• Subject requires long term antibiotic therapy (eg, Lyme Disease, tuberculosis).

• Subject has known or suspected alcohol abuse or illicit drug use within 1 year of enrollment.

• Subject has participated in an investigational drug or device study within the 30 days prior to randomization.

• Subject has received rifaximin within the last 30 days.

• Subject has concomitant disease or condition that could interfere with, or for which treatment could interfere with the conduct of the study, or could in the opinion of the investigator increase the risk of AEs for the subject's participation in the study.

• Subject is unwilling or unable to comply with the study protocol for any other reason.

• Subject has been diagnosed with other forms of liver disease, including those with HIV and HBV co-infection, as determined by history, serological parameters, and histology when available.

• Subject has been diagnosed with a major psychiatric illness, chronic renal and/or respiratory insufficiency, intercurrent infections, treatment with sedatives within 7 days of enrollment.

• Subject shows presence of intestinal obstruction or inflammatory bowel disease, antacids or cathartics within the 12h before study start; antibiotics during 7 days before start of dosing; or treated with encephalopathy-causing agents.

• Subjects with bad vision or neurological diseases since they could have difficulty completing the neuropsychological assessments.

Phase B Inclusion Criteria

• Subject successfully participated in and continues to meet all eligibility criteria required in Phase A of the study based on completion of tests, Breath Tests, and Radiological Marker.

• Subject has a Number Connection Test score >50 sec at time of enrollment.

Phase B Exclusion Criteria

• A subject will not be eligible for inclusion in Phase B if (s)he meets any of the exclusion criteria for Phase A of the study.