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

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01904409
• Other study ID #: RNLC2131
• Status: Completed
• Phase: Phase 2
• Start date: June 2013
• Est. completion date: July 2015

Study information

• Verified date: October 2019
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: July 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• Placebo

• Rifaximin SSD 40 mg IR tablet

• Rifaximin SSD 80 mg IR tablet

• Rifaximin SSD 40 mg SER tablet

• Rifaximin SSD 80 mg SER tablet

• Rifaximin SSD 80mgIR/80mgSER tablet

Locations

Country	Name	City	State
Russian Federation	Salix Investigative Site	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
United States	Salix Investigational Site	Annapolis	Maryland
United States	Salix Investigative Site	Arlington	Texas
United States	Salix Investigational Site	Artesia	California
United States	Salix Investigational Site	Asheville	North Carolina
United States	Salix Investigational Site	Atlanta	Georgia
United States	Salix Investigative Site	Atlanta	Georgia
United States	Salix Investigational Site	Austin	Texas
United States	Salix Investigational Site	Bakersfield	California
United States	Salix Investigational Site	Baltimore	Maryland
United States	Salix Investigational Site	Baltimore	Maryland
United States	Salix Investigational Site	Bastrop	Louisiana
United States	Salix Investigative Site	Birmingham	Alabama
United States	Salix Investigational Site	Boston	Massachusetts
United States	Salix Investigational Site	Boston	Massachusetts
United States	Salix Investigational Site	Bountiful	Utah
United States	Salix Investigational Site	Bowling Green	Kentucky
United States	Salix Investigational Site	Bristol	Connecticut
United States	Salix Investigative Site	Bristol	Tennessee
United States	Salix Investigational Site	Brockton	Massachusetts
United States	Salix Investigative Site	Bronx	New York
United States	Salix Investigative Site	Brooklyn	New York
United States	Salix Investigational Site	Chapel Hill	North Carolina
United States	Salix Investigational Site	Charlotte	North Carolina
United States	Salix Investigative Site	Charlotte	North Carolina
United States	Salix Investigational Site	Charlottesville	Virginia
United States	Salix Investigational Site	Chattanooga	Tennessee
United States	Salix Investigative Site	Chesterfield	Michigan
United States	Salix Investigational Site	Chevy Chase	Maryland
United States	Salix Investigative Site	Chicago	Illinois
United States	Salix Investigational Site	Chula Vista	California
United States	Salix Investigational Site	Cincinnati	Ohio
United States	Salix Investigative Site	Cincinnati	Ohio
United States	Salix Investigational Site	Cleveland	Ohio
United States	Salix Investigational Site	Coral Gables	Florida
United States	Salix Investigational Site	Coronado	California
United States	Salix Investigational Site	Costa Mesa	California
United States	Salix Investigational Site	Dallas	Texas
United States	Salix Investigational Site	Dallas	Texas
United States	Salix Investigative Site	Dallas	Texas
United States	Salix Investigative Site	Dayton	Ohio
United States	Salix Investigative Site	Decatur	Georgia
United States	Salix Investigative Site	Dothan	Alabama
United States	Salix Investigational Site	Englewood	Colorado
United States	Salix Investigational Site	Evansville	Indiana
United States	Salix Investigational Site	Fayetteville	North Carolina
United States	Salix Investigational Site	Flushing	New York
United States	Salix Investigational Site	Fort Worth	Texas
United States	Salix Investigative Site	Fresno	California
United States	Salix Investigational Site	Gainesville	Florida
United States	Salix Investigational Site	Hagerstown	Maryland
United States	Salix Investigational Site	Hialeah	Florida
United States	Salix Investigative Site	Hialeah	Florida
United States	Salix Investigational Site	Hollywood	Florida
United States	Salix Investigational Site	Houston	Texas
United States	Salix Investigational Site	Houston	Texas
United States	Salix Investigational Site	Houston	Texas
United States	Salix Investigational Site	Indianapolis	Indiana
United States	Salix Investigative Site	Inverness	Florida
United States	Salix Investigative Site	Iowa City	Iowa
United States	Salix Investigational Site	Kansas City	Missouri
United States	Salix Investigational Site	La Jolla	California
United States	Salix Investigational Site	Lake Worth	Florida
United States	Salix Investigative Site	Largo	Florida
United States	Salix Investigational Site	Littleton	Colorado
United States	Salix Investigative Site	Los Angeles	California
United States	Salix Investigational Site	Macon	Georgia
United States	Salix Investigative Site	Maitland	Florida
United States	Salix Investigational Site	Marlton	New Jersey
United States	Salix Investigative Site	Maywood	Illinois
United States	Salix Investigational Site	Mentor	Ohio
United States	Salix Investigational Site	Miami	Florida
United States	Salix Investigational Site	Miami	Florida
United States	Salix Investigational Site	Miami	Florida
United States	Salix Investigational Site	Miami Springs	Florida
United States	Salix Investigational Site	Minneapolis	Minnesota
United States	Salix Investigative Site	Mobile	Alabama
United States	Salix Investigational Site	Monroe	Louisiana
United States	Salix Investigational Site	Monterey	California
United States	Salix Investigational Site	Nashville	Tennessee
United States	Salix Investigational Site	Nashville	Tennessee
United States	Salix Investigational Site	New Brunswick	New Jersey
United States	Salix Investigational Site	New Haven	Connecticut
United States	Salix Investigational Site	New Orleans	Louisiana
United States	Salix Investigational Site	New Port Richey	Florida
United States	Salix Investigational Site	New York	New York
United States	Salix Investigational Site	New York	New York
United States	Salix Investigative Site	Norfolk	Virginia
United States	Salix Investigative Site	Orlando	Florida
United States	Salix Investigational Site	Pembroke Pines	Florida
United States	Salix Investigational Site	Port Orange	Florida
United States	Salix Investigational Site	Portland	Oregon
United States	Salix Investigative Site	Richland	Washington
United States	Salix Investigational Site	Richmond	Virginia
United States	Salix Investigative Site	Richmond	Virginia
United States	Salix Investigational Site	Riverside	California
United States	Salix Investigational Site	Rochester	New York
United States	Salix Investigational Site	Saint Cloud	Florida
United States	Salix Investigative Site	Saint Louis	Missouri
United States	Salix Investigative Site	Salt Lake City	Utah
United States	Salix Investigational Site	San Antonio	Texas
United States	Salix Investigational Site	San Antonio	Texas
United States	Salix Investigational Site	San Diego	California
United States	Salix Investigative Site	Seattle	Washington
United States	Salix Investigational Site	Shreveport	Louisiana
United States	Salix Investigational Site	Springfield	Massachusetts
United States	Salix Investigational Site	Tamarac	Florida
United States	Salix Investigative Site	Tucson	Arizona
United States	Salix Investigative Site	Tupelo	Mississippi
United States	Salix Investigational Site	Ventura	California
United States	Salix Investigational Site	Waterbury	Connecticut
United States	Salix Investigational Site	Wilmington	North Carolina
United States	Salix Investigational Site	Winston-Salem	North Carolina
United States	Salix Investigational Site	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.

Countries where clinical trial is conducted

United States,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to all-cause mortality or hospitalization that is attributable to complications of liver disease.	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	Overall hospitalization rate due to each complication of liver disease or all-cause mortality over the 24-week treatment period.	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
Secondary	Pharmacokinetics of rifaximin and its metabolite.	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
Secondary	Incidence of treatment-emergent adverse events.	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
Secondary	Change in clinical laboratory parameters.	This outcome will measure the changes in each patient's clinical laboratory test results during the treatment period.	Weeks 1 through 24
Secondary	Changes in electrocardiogram measurements	This outcome will measure the changes in measurements obtained from 12-lead electrocardiograms for each patient during the treatment period.	Weeks 1 through 24
Secondary	Changes in indices of health outcomes	This outcome will evaluate each patient's responses on questionnaires that assess health status.	Weeks, 4, 8, 12, 16, and 24