Dose-ranging Study of Rifaximin Soluble Solid Dispersion (SSD) Tablets for the Prevention of Complications of Early Decompensated Liver Cirrhosis

October 15, 2019 updated by: Bausch Health Americas, Inc.

A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Multicenter Study to Assess the Efficacy and Safety of Rifaximin Soluble Solid Dispersion (SSD) Tablets for the Prevention of Complications in Subjects With Early Decompensated Liver Cirrhosis

The primary objective of this study is to assess the efficacy of rifaximin SSD versus placebo in preventing complications of liver cirrhosis, such as all-cause mortality (death due to all causes) or hospitalization, in subjects with early decompensated liver cirrhosis.

Rifaximin, a non-systemic antibacterial agent, is currently marketed as a 550 mg tablet for the reduction in risk of recurrent overt hepatic encephalopathy, a complication of liver cirrhosis. The rifaximin SSD tablet was formulated to maximize the efficacy of rifaximin.

Subjects will receive 1 of 5 doses of rifaximin SSD tablets or placebo tablets every day for 24 weeks.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

420

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Krasnogorsk, Russian Federation
        • Salix Investigative Site
      • Moscow, Russian Federation
        • Salix Investigative Site
      • Novosibirsk, Russian Federation
        • Salix Investigative Site
      • Petersburg, Russian Federation
        • Salix Investigative Site
      • Samara, Russian Federation
        • Salix Investigative Site
      • Smolensk, Russian Federation
        • Salix Investigative Site
      • St. Petersburg, Russian Federation
        • Salix Investigative Site
      • Stavropol, Russian Federation
        • Salix Investigative Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Salix Investigative Site
      • Dothan, Alabama, United States, 36305
        • Salix Investigative Site
      • Mobile, Alabama, United States, 36617
        • Salix Investigative Site
    • Arizona
      • Tucson, Arizona, United States, 85712
        • Salix Investigative Site
    • California
      • Artesia, California, United States, 90701
        • Salix Investigational Site
      • Bakersfield, California, United States, 93301
        • Salix Investigational Site
      • Chula Vista, California, United States, 91910
        • Salix Investigational Site
      • Coronado, California, United States, 92118
        • Salix Investigational Site
      • Costa Mesa, California, United States, 92626
        • Salix Investigational Site
      • Fresno, California, United States, 93701
        • Salix Investigative Site
      • La Jolla, California, United States, 92037
        • Salix Investigational Site
      • Los Angeles, California, United States, 90033
        • Salix Investigative Site
      • Monterey, California, United States, 93940
        • Salix Investigational Site
      • Riverside, California, United States, 92377
        • Salix Investigational Site
      • San Diego, California, United States, 92114
        • Salix Investigational Site
      • Ventura, California, United States, 93003
        • Salix Investigational Site
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Salix Investigational Site
      • Littleton, Colorado, United States, 80120
        • Salix Investigational Site
    • Connecticut
      • Bristol, Connecticut, United States, 06035
        • Salix Investigational Site
      • New Haven, Connecticut, United States, 06520
        • Salix Investigational Site
      • Waterbury, Connecticut, United States, 06708
        • Salix Investigational Site
    • Florida
      • Coral Gables, Florida, United States, 33134
        • Salix Investigational Site
      • Gainesville, Florida, United States, 32610
        • Salix Investigational Site
      • Hialeah, Florida, United States, 33012
        • Salix Investigative Site
      • Hialeah, Florida, United States, 33016
        • Salix Investigational Site
      • Hollywood, Florida, United States, 33021
        • Salix Investigational Site
      • Inverness, Florida, United States, 34452
        • Salix Investigative Site
      • Lake Worth, Florida, United States, 33449
        • Salix Investigational Site
      • Largo, Florida, United States, 33777
        • Salix Investigative Site
      • Maitland, Florida, United States, 32751
        • Salix Investigative Site
      • Miami, Florida, United States, 33030
        • Salix Investigational Site
      • Miami, Florida, United States, 33126
        • Salix Investigational Site
      • Miami, Florida, United States, 33136
        • Salix Investigational Site
      • Miami Springs, Florida, United States, 33166
        • Salix Investigational Site
      • New Port Richey, Florida, United States, 34653
        • Salix Investigational Site
      • Orlando, Florida, United States, 32824
        • Salix Investigative Site
      • Pembroke Pines, Florida, United States, 33024
        • Salix Investigational Site
      • Port Orange, Florida, United States, 32127
        • Salix Investigational Site
      • Saint Cloud, Florida, United States, 34769
        • Salix Investigational Site
      • Tamarac, Florida, United States, 33319
        • Salix Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Salix Investigational Site
      • Atlanta, Georgia, United States, 30342
        • Salix Investigative Site
      • Decatur, Georgia, United States, 30033
        • Salix Investigative Site
      • Macon, Georgia, United States, 31201
        • Salix Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Salix Investigative Site
      • Maywood, Illinois, United States, 75390
        • Salix Investigative Site
    • Indiana
      • Evansville, Indiana, United States, 47714
        • Salix Investigational Site
      • Indianapolis, Indiana, United States, 46202
        • Salix Investigational Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Salix Investigative Site
    • Kentucky
      • Bowling Green, Kentucky, United States, 42101
        • Salix Investigational Site
    • Louisiana
      • Bastrop, Louisiana, United States, 71220
        • Salix Investigational Site
      • Monroe, Louisiana, United States, 71201
        • Salix Investigational Site
      • New Orleans, Louisiana, United States, 70112
        • Salix Investigational Site
      • Shreveport, Louisiana, United States, 71103
        • Salix Investigational Site
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Salix Investigational Site
      • Baltimore, Maryland, United States, 21202
        • Salix Investigational Site
      • Baltimore, Maryland, United States, 21228
        • Salix Investigational Site
      • Chevy Chase, Maryland, United States, 20815
        • Salix Investigational Site
      • Hagerstown, Maryland, United States, 21743
        • Salix Investigational Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Salix Investigational Site
      • Boston, Massachusetts, United States, 02115
        • Salix Investigational Site
      • Brockton, Massachusetts, United States, 02302
        • Salix Investigational Site
      • Springfield, Massachusetts, United States, 01105
        • Salix Investigational Site
    • Michigan
      • Chesterfield, Michigan, United States, 48047
        • Salix Investigative Site
      • Wyoming, Michigan, United States, 49519
        • Salix Investigational Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Salix Investigational Site
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • Salix Investigative Site
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Salix Investigational Site
      • Saint Louis, Missouri, United States, 63110
        • Salix Investigative Site
    • New Jersey
      • Marlton, New Jersey, United States, 08053
        • Salix Investigational Site
      • New Brunswick, New Jersey, United States, 07102
        • Salix Investigational Site
    • New York
      • Bronx, New York, United States, 10467
        • Salix Investigative Site
      • Brooklyn, New York, United States, 60153
        • Salix Investigative Site
      • Flushing, New York, United States, 11040
        • Salix Investigational Site
      • New York, New York, United States, 10016
        • Salix Investigational Site
      • New York, New York, United States, 10032
        • Salix Investigational Site
      • Rochester, New York, United States, 14642
        • Salix Investigational Site
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Salix Investigational Site
      • Chapel Hill, North Carolina, United States, 27599
        • Salix Investigational Site
      • Charlotte, North Carolina, United States, 28204
        • Salix Investigative Site
      • Charlotte, North Carolina, United States, 28207
        • Salix Investigational Site
      • Fayetteville, North Carolina, United States, 28304
        • Salix Investigational Site
      • Wilmington, North Carolina, United States, 28403
        • Salix Investigational Site
      • Winston-Salem, North Carolina, United States, 27103
        • Salix Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45224
        • Salix Investigative Site
      • Cincinnati, Ohio, United States, 45249
        • Salix Investigational Site
      • Cleveland, Ohio, United States, 44195
        • Salix Investigational Site
      • Dayton, Ohio, United States, 45415
        • Salix Investigative Site
      • Mentor, Ohio, United States, 44060
        • Salix Investigational Site
    • Oregon
      • Portland, Oregon, United States, 97210
        • Salix Investigational Site
    • Tennessee
      • Bristol, Tennessee, United States, 37620
        • Salix Investigative Site
      • Chattanooga, Tennessee, United States, 37421
        • Salix Investigational Site
      • Nashville, Tennessee, United States, 37205
        • Salix Investigational Site
      • Nashville, Tennessee, United States, 37211
        • Salix Investigational Site
    • Texas
      • Arlington, Texas, United States, 76012
        • Salix Investigative Site
      • Austin, Texas, United States, 78705
        • Salix Investigational Site
      • Dallas, Texas, United States, 75203
        • Salix Investigational Site
      • Dallas, Texas, United States, 75246
        • Salix Investigational Site
      • Dallas, Texas, United States, 75390
        • Salix Investigative Site
      • Fort Worth, Texas, United States, 76104
        • Salix Investigational Site
      • Houston, Texas, United States, 77030
        • Salix Investigational Site
      • Houston, Texas, United States, 77005
        • Salix Investigational Site
      • Houston, Texas, United States, 77090
        • Salix Investigational Site
      • San Antonio, Texas, United States, 78215
        • Salix Investigational Site
      • San Antonio, Texas, United States, 78229
        • Salix Investigational Site
    • Utah
      • Bountiful, Utah, United States, 84010
        • Salix Investigational Site
      • Salt Lake City, Utah, United States, 84132
        • Salix Investigative Site
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Salix Investigational Site
      • Norfolk, Virginia, United States, 23502
        • Salix Investigative Site
      • Richmond, Virginia, United States, 23249
        • Salix Investigative Site
      • Richmond, Virginia, United States, 23298
        • Salix Investigational Site
    • Washington
      • Richland, Washington, United States, 99352
        • Salix Investigative Site
      • Seattle, Washington, United States, 98104
        • Salix Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of liver cirrhosis and documented ascites.
  • Model End Stage Liver Disease (MELD) score of at least 12, MELD Na of at least 12, or Child-Pugh B (score of 7 - 9).
  • If applicable, has a close family or other personal contacts who can provide continuing oversight to the patient and will be available to the patient during the conduct of the trial.
  • If female of childbearing potential, have a negative serum pregnancy test at study start and agree to use an acceptable method of contraception during the study.

Exclusion Criteria:

  • History of a major psychiatric disorder including uncontrolled major depression or controlled or uncontrolled psychoses within the past 24 months prior to study start.
  • History of alcohol abuse or substance abuse within the past 3 months prior to study start.
  • Documented cholestatic liver disease such as primary sclerosing cholangitis.
  • Had prophylactic variceal banding within 2 weeks or is scheduled to undergo prophylactic banding during the study.
  • Diagnosed with an infection for which the patient is currently taking oral or parenteral antibiotics.
  • Significant hypovolemia, or any electrolyte abnormality that can affect mental function (eg, serum sodium < 125 mEq/L, serum calcium > 10 mg/dL).
  • Severe hypokalemia, defined as serum potassium concentration < 2.5 mEq/L.
  • Anemic, defined as hemoglobin concentration ≤ 8 g/dL.
  • Renal insufficiency with a creatinine of ≥ 1.5 mg/dL.
  • Presence of intestinal obstruction or inflammatory bowel disease.
  • Uncontrolled Type 1 or Type 2 diabetes.
  • History of seizure disorders.
  • Unstable cardiovascular or pulmonary disease, categorized by a worsening in the disease condition that requires a change in treatment or medical care within 30 days of study start.
  • Active malignancy within the last 5 years (exceptions: basal cell carcinomas of the skin, or if female, in situ cervical carcinoma that has been surgically excised).
  • Has hepatocellular carcinoma.
  • Known human immunodeficiency virus, varicella, herpes zoster, or other severe viral infection within 6 weeks of study start.
  • Positive stool test for Yersinia enterocolitica, Campylobacter jejuni, Salmonella, Shigella, ovum and parasites, and/or Clostridium difficile (C. difficile); determined during the screening period prior to study start.
  • History of tuberculosis infection and/or has received treatment for a tuberculosis infection.
  • History of hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any of the components of rifaximin soluble solid dispersion.
  • Used any investigational product or device, or participated in another research study within 30 days prior to study start.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo tablets once daily.
Drug: Placebo
Experimental: Rifaximin SSD 40 mg IR tablet
Rifaximin soluble solid dispersion (SSD) 40 mg immediate release (IR) tablet once daily.
Drug: Rifaximin SSD 40 mg IR tablet
Other Names:
  • Rifaximin
Experimental: Rifaximin SSD 80 mg IR tablet
Rifaximin soluble solid dispersion (SSD) 80 mg immediate release (IR) tablet once daily.
Drug: Rifaximin SSD 80 mg IR tablet
Other Names:
  • Rifaximin
Experimental: Rifaximin SSD 40 mg SER tablet
Rifaximin soluble solid dispersion (SSD) 40 mg sustained extended release (SER) tablet once daily.
Drug: Rifaximin SSD 40 mg SER tablet
Other Names:
  • Rifaximin
Experimental: Rifaximin SSD 80 mg SER tablet
Rifaximin soluble solid dispersion (SSD) 80 mg sustained extended release(SER) tablet once daily.
Drug: Rifaximin SSD 80 mg SER tablet
Other Names:
  • Rifaximin
Experimental: Rifaximin SSD 80mgIR/80mgSER tablet
Rifaximin soluble solid dispersion (SSD) 80 mg immediate release (IR) tablet + rifaximin SSD 80 mg sustained extended release (SER) tablet once daily.
Drug: Rifaximin SSD 80mgIR/80mgSER tablet
Other Names:
  • Rifaximin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to all-cause mortality or hospitalization that is attributable to complications of liver disease.
Time Frame: Weeks 1 through 24
The primary outcome measure will evaluate the time from start of the treatment period to death due to any cause (all-cause mortality) or hospitalization due to complications of liver disease for each patient during the 24-week treatment period.
Weeks 1 through 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall hospitalization rate due to each complication of liver disease or all-cause mortality over the 24-week treatment period.
Time Frame: Weeks 1 through 24
This outcome measure will determine the rate of hospitalization (percentage of patients who are hospitalized) due to each complication of liver disease or all-cause mortality over the 24-week treatment period.
Weeks 1 through 24
Pharmacokinetics of rifaximin and its metabolite.
Time Frame: Weeks 1 through 24
This outcome will measure the plasma levels of rifaximin and its metabolite (25-desacetyl rifaximin) for each patient during the 24-week treatment period.
Weeks 1 through 24
Incidence of treatment-emergent adverse events.
Time Frame: Weeks 1 through 24
This outcome will evaluate the incidence of treatment-emergent adverse events (percentage of patients who experience adverse events following the start of the treatment period).
Weeks 1 through 24
Change in clinical laboratory parameters.
Time Frame: Weeks 1 through 24
This outcome will measure the changes in each patient's clinical laboratory test results during the treatment period.
Weeks 1 through 24
Changes in electrocardiogram measurements
Time Frame: Weeks 1 through 24
This outcome will measure the changes in measurements obtained from 12-lead electrocardiograms for each patient during the treatment period.
Weeks 1 through 24
Changes in indices of health outcomes
Time Frame: Weeks, 4, 8, 12, 16, and 24
This outcome will evaluate each patient's responses on questionnaires that assess health status.
Weeks, 4, 8, 12, 16, and 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bausch Health Americas, Inc.

Investigators

  • Study Director: James Joffrion, Bausch Health Americas, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2013

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

July 17, 2013

First Submitted That Met QC Criteria

July 19, 2013

First Posted (Estimate)

July 22, 2013

Study Record Updates

Last Update Posted (Actual)

October 23, 2019

Last Update Submitted That Met QC Criteria

October 15, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RNLC2131

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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