Clinical trial NCT01904409: Dose-ranging Study of Rifaximin Soluble Solid Dispersion (SSD) Tablets for the Prevention of Complications of Early Decompensated Liver Cirrhosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Cirrhosis
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-22
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to all-cause mortality or hospitalization that is attributable to complications of liver disease.
timeFrame: Weeks 1 through 24
Secondary outcomes:
measure: Overall hospitalization rate due to each complication of liver disease or all-cause mortality over the 24-week treatment period.
timeFrame: Weeks 1 through 24
measure: Pharmacokinetics of rifaximin and its metabolite.
timeFrame: Weeks 1 through 24
measure: Incidence of treatment-emergent adverse events.
timeFrame: Weeks 1 through 24
measure: Change in clinical laboratory parameters.
timeFrame: Weeks 1 through 24
measure: Changes in electrocardiogram measurements
timeFrame: Weeks 1 through 24
measure: Changes in indices of health outcomes
timeFrame: Weeks, 4, 8, 12, 16, and 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Salix Investigative Site
state: Alabama
city: Dothan
country: United States
facility: Salix Investigative Site
state: Alabama
city: Mobile
country: United States
facility: Salix Investigative Site
state: Alabama
city: Tucson
country: United States
facility: Salix Investigative Site
state: Arizona
city: Artesia
country: United States
facility: Salix Investigational Site
state: California
city: Bakersfield
country: United States
facility: Salix Investigational Site
state: California
city: Chula Vista
country: United States
facility: Salix Investigational Site
state: California
city: Coronado
country: United States
facility: Salix Investigational Site
state: California
city: Costa Mesa
country: United States
facility: Salix Investigational Site
state: California
city: Fresno
country: United States
facility: Salix Investigative Site
state: California
city: La Jolla
country: United States
facility: Salix Investigational Site
state: California
city: Los Angeles
country: United States
facility: Salix Investigative Site
state: California
city: Monterey
country: United States
facility: Salix Investigational Site
state: California
city: Riverside
country: United States
facility: Salix Investigational Site
state: California
city: San Diego
country: United States
facility: Salix Investigational Site
state: California
city: Ventura
country: United States
facility: Salix Investigational Site
state: California
city: Englewood
country: United States
facility: Salix Investigational Site
state: Colorado
city: Littleton
country: United States
facility: Salix Investigational Site
state: Colorado
city: Bristol
country: United States
facility: Salix Investigational Site
state: Connecticut
city: New Haven
country: United States
facility: Salix Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: Salix Investigational Site
state: Connecticut
city: Coral Gables
country: United States
facility: Salix Investigational Site
state: Florida
city: Gainesville
country: United States
facility: Salix Investigational Site
state: Florida
city: Hialeah
country: United States
facility: Salix Investigative Site
state: Florida
city: Hialeah
country: United States
facility: Salix Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Salix Investigational Site
state: Florida
city: Inverness
country: United States
facility: Salix Investigative Site
state: Florida
city: Lake Worth
country: United States
facility: Salix Investigational Site
state: Florida
city: Largo
country: United States
facility: Salix Investigative Site
state: Florida
city: Maitland
country: United States
facility: Salix Investigative Site
state: Florida
city: Miami Springs
country: United States
facility: Salix Investigational Site
state: Florida
city: Miami
country: United States
facility: Salix Investigational Site
state: Florida
city: Miami
country: United States
facility: Salix Investigational Site
state: Florida
city: Miami
country: United States
facility: Salix Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Salix Investigational Site
state: Florida
city: Orlando
country: United States
facility: Salix Investigative Site
state: Florida
city: Pembroke Pines
country: United States
facility: Salix Investigational Site
state: Florida
city: Port Orange
country: United States
facility: Salix Investigational Site
state: Florida
city: Saint Cloud
country: United States
facility: Salix Investigational Site
state: Florida
city: Tamarac
country: United States
facility: Salix Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Salix Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Salix Investigative Site
state: Georgia
city: Decatur
country: United States
facility: Salix Investigative Site
state: Georgia
city: Macon
country: United States
facility: Salix Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Salix Investigative Site
state: Illinois
city: Maywood
country: United States
facility: Salix Investigative Site
state: Illinois
city: Evansville
country: United States
facility: Salix Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: Salix Investigational Site
state: Indiana
city: Iowa City
country: United States
facility: Salix Investigative Site
state: Iowa
city: Bowling Green
country: United States
facility: Salix Investigational Site
state: Kentucky
city: Bastrop
country: United States
facility: Salix Investigational Site
state: Louisiana
city: Monroe
country: United States
facility: Salix Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: Salix Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: Salix Investigational Site
state: Louisiana
city: Annapolis
country: United States
facility: Salix Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Salix Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Salix Investigational Site
state: Maryland
city: Chevy Chase
country: United States
facility: Salix Investigational Site
state: Maryland
city: Hagerstown
country: United States
facility: Salix Investigational Site
state: Maryland
city: Boston
country: United States
facility: Salix Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Salix Investigational Site
state: Massachusetts
city: Brockton
country: United States
facility: Salix Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Salix Investigational Site
state: Massachusetts
city: Chesterfield
country: United States
facility: Salix Investigative Site
state: Michigan
city: Wyoming
country: United States
facility: Salix Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Salix Investigational Site
state: Minnesota
city: Tupelo
country: United States
facility: Salix Investigative Site
state: Mississippi
city: Kansas City
country: United States
facility: Salix Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Salix Investigative Site
state: Missouri
city: Marlton
country: United States
facility: Salix Investigational Site
state: New Jersey
city: New Brunswick
country: United States
facility: Salix Investigational Site
state: New Jersey
city: Bronx
country: United States
facility: Salix Investigative Site
state: New York
city: Brooklyn
country: United States
facility: Salix Investigative Site
state: New York
city: Flushing
country: United States
facility: Salix Investigational Site
state: New York
city: New York
country: United States
facility: Salix Investigational Site
state: New York
city: New York
country: United States
facility: Salix Investigational Site
state: New York
city: Rochester
country: United States
facility: Salix Investigational Site
state: New York
city: Asheville
country: United States
facility: Salix Investigational Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Salix Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Salix Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Salix Investigational Site
state: North Carolina
city: Fayetteville
country: United States
facility: Salix Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Salix Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Salix Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Salix Investigative Site
state: Ohio
city: Cincinnati
country: United States
facility: Salix Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Salix Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Salix Investigative Site
state: Ohio
city: Mentor
country: United States
facility: Salix Investigational Site
state: Ohio
city: Portland
country: United States
facility: Salix Investigational Site
state: Oregon
city: Bristol
country: United States
facility: Salix Investigative Site
state: Tennessee
city: Chattanooga
country: United States
facility: Salix Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Salix Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Salix Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: Salix Investigative Site
state: Texas
city: Austin
country: United States
facility: Salix Investigational Site
state: Texas
city: Dallas
country: United States
facility: Salix Investigational Site
state: Texas
city: Dallas
country: United States
facility: Salix Investigational Site
state: Texas
city: Dallas
country: United States
facility: Salix Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Salix Investigational Site
state: Texas
city: Houston
country: United States
facility: Salix Investigational Site
state: Texas
city: Houston
country: United States
facility: Salix Investigational Site
state: Texas
city: Houston
country: United States
facility: Salix Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Salix Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Salix Investigational Site
state: Texas
city: Bountiful
country: United States
facility: Salix Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Salix Investigative Site
state: Utah
city: Charlottesville
country: United States
facility: Salix Investigational Site
state: Virginia
city: Norfolk
country: United States
facility: Salix Investigative Site
state: Virginia
city: Richmond
country: United States
facility: Salix Investigative Site
state: Virginia
city: Richmond
country: United States
facility: Salix Investigational Site
state: Virginia
city: Richland
country: United States
facility: Salix Investigative Site
state: Washington
city: Seattle
country: United States
facility: Salix Investigative Site
state: Washington
city: Krasnogorsk
country: Russian Federation
facility: Salix Investigative Site
city: Moscow
country: Russian Federation
facility: Salix Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Salix Investigative Site
city: Petersburg
country: Russian Federation
facility: Salix Investigative Site
city: Samara
country: Russian Federation
facility: Salix Investigative Site
city: Smolensk
country: Russian Federation
facility: Salix Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Salix Investigative Site
city: Stavropol
country: Russian Federation
facility: Salix Investigative Site
Study officials:
affiliation: Bausch Health Americas, Inc.
name: James Joffrion
role: STUDY_DIRECTOR
References:
citation: Bajaj JS, Hassanein TI, Pyrsopoulos NT, Sanyal AJ, Rahimi RS, Heimanson Z, Israel RJ, Rockey DC. Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials. Clin Gastroenterol Hepatol. 2023 Mar;21(3):723-731.e9. doi: 10.1016/j.cgh.2022.05.042. Epub 2022 Jun 22.