Safety and Tolerability Study of Rifaximin in Participants With a History of Hepatic Encephalopathy

Study Overview
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Brief Summary
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This study will look at the safety of a drug used in participants who have had hepatic encephalopathy (HE) in the past.

Detailed Description
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Eligible participants had a history of HE, a Conn score of 0 to 2 at enrollment, and either had successfully participated in a previous HE study with rifaximin (that is, RFHE3001 [NCT00298038]), or were new participants enrolled with ≥1 verifiable episode of HE (equivalent to a Conn score of ≥2) associated with cirrhosis or portal hypertension within 12 months of screening. Successful participation in a previous rifaximin study was defined as having received ≥80% and ≤120% of the expected tablets, having been reasonably compliant with study procedures, and having not been discontinued from the previous study due to study drug-related Adverse Events. Participants who experienced HE or associated symptoms during or after the RFHE3001 study were considered eligible for entry into this open-label study if the participant and Investigator did not perceive study medication as a possible cause of the HE episode or associated symptoms. Participants who did not participate in a previous HE study with rifaximin were eligible if this open-label study was the only rifaximin HE study available at an individual site.

Official Title
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A Multi-Center, Open-Label Trial to Evaluate the Long-Term Safety and Tolerability of Rifaximin 550 mg BID in Subjects With a History of Hepatic Encephalopathy

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: Rifaximin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must sign an Informed Consent Form In remission from past HE Appropriate birth control measures More than or equal to 18 years of age Must be potential for benefit from treatment Recent HE episodes Capable and willing to comply with all study procedures Participant has support network Exclusion Criteria: Significant medical conditions or Investigator decision not to include the participant Allergies to the study drug or similar drugs Laboratory abnormalities Recent participation in another clinical trial Problems experienced in a previous HE trial Pregnant or at risk of pregnancy Recent alcohol consumption Active or latent bacterial or viral Infections Bowel issues Recent Active Cancer On a prohibited medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rifaximin<br>Participants from a previous rifaximin HE study and new participants were administered a single rifaximin 550 milligram (mg) tablet 2 times per day (approximately every 12 hours) for at least 24 months, until regulatory approval of rifaximin for reduction in risk of overt HE recurrence, or until the sponsor closed the study. | Drug: Rifaximin<br>* Oral<br>* Other names: Xifaxan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants Reporting A Non-serious Adverse Event Or A Serious Adverse Event | A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. | Baseline up to Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants With Postbaseline Potentially Clinically Significant Laboratory (Hematology and Blood Chemistry) Abnormal Results In ≥5% of Participants | Hematology and blood chemistry with potentially significant values included: Hemoglobin <9, >18, or ≥3 (grams/deciliter [g/dL]) decrease from previous visit or ≥4 g/dL decrease from baseline; Hematocrit <0.27%, >0.54%, or ≥0.10% decrease from previous visit or ≥0.15% decrease from baseline; Platelets <50 or >400*10^9/(liter [L]); Prothrombin time 9 seconds above baseline or upper limit of normal range; International normalized ratio >1.7; White blood cells <2.0 or >12.0*10^9/L; Lymphocytes <13.5% or >70%; Glucose, random, serum <2.2 or >16.5 millimole (mmol)/L; Potassium ≤3.0 or ≥5.5 mmol/L; Direct bilirubin increases 3-fold from baseline or >85.5 micromole (umol)/L. Baseline value was defined as the last available value (including the applicable values from the participants who rolled over from Study RFHE3001) prior to the first dose of study drug. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. | Baseline up to Month 36 | 
| Number Of Participants With A Significant Mean Change From Baseline In Vital Signs | Vital signs were measured and included sitting blood pressure, heart rate, oral temperature, and weight. These were collected at each scheduled study visit. Participants were placed supine for 5 minutes prior to each assessment of vital signs. Baseline value was defined as last available value (including the applicable values from the participants who rolled over from Study RFHE3001) prior to the first dose of study drug. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. | Baseline up to Month 36 | 
| Change From Baseline In Conn Score At Last Assessment | The assessment for change in mental status during the study was measured by the Conn score (also known as the West Haven score). The following scale was used in the Conn scoring system: Grade 0=No personality or behavioral abnormality detected. Grade 1=Trivial lack of awareness, euphoria, or anxiety; shortened attention span; or impairment of addition or subtraction. Grade 2=Lethargy; disorientation for time; obvious personality change; and inappropriate behavior. Grade 3=Somnolence to semi-stupor, responsive to stimuli; confused; gross disorientation; and bizarre behavior. Grade 4=Coma, unable to test mental state. Participants entered the study with a Conn score of 0 to 2. Baseline value was defined as last available value (including the applicable values from the participants who rolled over from Study RFHE3001) prior to the first dose of study drug. | Baseline up to Month 36 |