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

NCT01904409 | Completed Phase 2 DMC

• 1 other identifier: RNLC2131
• Study Type: interventional
• Target: 420
• Locations: 2 countries
• Sites: 120

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.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall hospitalization rate 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.

  Weeks 1 through 24

• Incidence of treatment-emergent adverse events.

  Weeks 1 through 24

• Change in clinical laboratory parameters.

  Weeks 1 through 24

• Changes in electrocardiogram measurements

  Weeks 1 through 24

Study Arms (6)

Placebo

PLACEBO COMPARATOR

Placebo tablets once daily.

Drug: Placebo

Rifaximin SSD 40 mg IR tablet

EXPERIMENTAL

Rifaximin soluble solid dispersion (SSD) 40 mg immediate release (IR) tablet once daily.

Drug: Rifaximin SSD 40 mg IR tablet

Rifaximin SSD 80 mg IR tablet

EXPERIMENTAL

Rifaximin soluble solid dispersion (SSD) 80 mg immediate release (IR) tablet once daily.

Drug: Rifaximin SSD 80 mg IR tablet

Rifaximin SSD 40 mg SER tablet

EXPERIMENTAL

Rifaximin soluble solid dispersion (SSD) 40 mg sustained extended release (SER) tablet once daily.

Drug: Rifaximin SSD 40 mg SER tablet

Rifaximin SSD 80 mg SER tablet

EXPERIMENTAL

Rifaximin soluble solid dispersion (SSD) 80 mg sustained extended release(SER) tablet once daily.

Drug: Rifaximin SSD 80 mg SER tablet

Rifaximin SSD 80mgIR/80mgSER tablet

EXPERIMENTAL

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

Interventions

Placebo DRUG

Placebo

Rifaximin SSD 40 mg IR tablet DRUG

Also known as: Rifaximin

Rifaximin SSD 40 mg IR tablet

Rifaximin SSD 80 mg IR tablet DRUG

Also known as: Rifaximin

Rifaximin SSD 80 mg IR tablet

Rifaximin SSD 40 mg SER tablet DRUG

Also known as: Rifaximin

Rifaximin SSD 40 mg SER tablet

Rifaximin SSD 80 mg SER tablet DRUG

Also known as: Rifaximin

Rifaximin SSD 80 mg SER tablet

Rifaximin SSD 80mgIR/80mgSER tablet DRUG

Also known as: Rifaximin

Rifaximin SSD 80mgIR/80mgSER tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bausch Health Americas, Inc.: lead

Study Sites (120)

Salix Investigative Site

Birmingham, Alabama, 35294, United States

Location

Salix Investigative Site

Dothan, Alabama, 36305, United States

Location

Salix Investigative Site

Mobile, Alabama, 36617, United States

Location

Salix Investigative Site

Tucson, Arizona, 85712, United States

Location

Salix Investigational Site

Artesia, California, 90701, United States

Location

Salix Investigational Site

Bakersfield, California, 93301, United States

Location

Salix Investigational Site

Chula Vista, California, 91910, United States

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Salix Investigational Site

Coronado, California, 92118, United States

Location

Salix Investigational Site

Costa Mesa, California, 92626, United States

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Salix Investigative Site

Fresno, California, 93701, United States

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Salix Investigational Site

La Jolla, California, 92037, United States

Location

Salix Investigative Site

Los Angeles, California, 90033, United States

Location

Salix Investigational Site

Monterey, California, 93940, United States

Location

Salix Investigational Site

Riverside, California, 92377, United States

Location

Salix Investigational Site

San Diego, California, 92114, United States

Location

Salix Investigational Site

Ventura, California, 93003, United States

Location

Salix Investigational Site

Englewood, Colorado, 80113, United States

Location

Salix Investigational Site

Littleton, Colorado, 80120, United States

Location

Salix Investigational Site

Bristol, Connecticut, 06035, United States

Location

Salix Investigational Site

New Haven, Connecticut, 06520, United States

Location

Salix Investigational Site

Waterbury, Connecticut, 06708, United States

Location

Salix Investigational Site

Coral Gables, Florida, 33134, United States

Location

Salix Investigational Site

Gainesville, Florida, 32610, United States

Location

Salix Investigative Site

Hialeah, Florida, 33012, United States

Location

Salix Investigational Site

Hialeah, Florida, 33016, United States

Location

Salix Investigational Site

Hollywood, Florida, 33021, United States

Location

Salix Investigative Site

Inverness, Florida, 34452, United States

Location

Salix Investigational Site

Lake Worth, Florida, 33449, United States

Location

Salix Investigative Site

Largo, Florida, 33777, United States

Location

Salix Investigative Site

Maitland, Florida, 32751, United States

Location

Salix Investigational Site

Miami, Florida, 33030, United States

Location

Salix Investigational Site

Miami, Florida, 33126, United States

Location

Salix Investigational Site

Miami, Florida, 33136, United States

Location

Salix Investigational Site

Miami Springs, Florida, 33166, United States

Location

Salix Investigational Site

New Port Richey, Florida, 34653, United States

Location

Salix Investigative Site

Orlando, Florida, 32824, United States

Location

Salix Investigational Site

Pembroke Pines, Florida, 33024, United States

Location

Salix Investigational Site

Port Orange, Florida, 32127, United States

Location

Salix Investigational Site

Saint Cloud, Florida, 34769, United States

Location

Salix Investigational Site

Tamarac, Florida, 33319, United States

Location

Salix Investigational Site

Atlanta, Georgia, 30309, United States

Location

Salix Investigative Site

Atlanta, Georgia, 30342, United States

Location

Salix Investigative Site

Decatur, Georgia, 30033, United States

Location

Salix Investigational Site

Macon, Georgia, 31201, United States

Location

Salix Investigative Site

Chicago, Illinois, 60612, United States

Location

Salix Investigative Site

Maywood, Illinois, 75390, United States

Location

Salix Investigational Site

Evansville, Indiana, 47714, United States

Location

Salix Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Salix Investigative Site

Iowa City, Iowa, 52242, United States

Location

Salix Investigational Site

Bowling Green, Kentucky, 42101, United States

Location

Salix Investigational Site

Bastrop, Louisiana, 71220, United States

Location

Salix Investigational Site

Monroe, Louisiana, 71201, United States

Location

Salix Investigational Site

New Orleans, Louisiana, 70112, United States

Location

Salix Investigational Site

Shreveport, Louisiana, 71103, United States

Location

Salix Investigational Site

Annapolis, Maryland, 21401, United States

Location

Salix Investigational Site

Baltimore, Maryland, 21202, United States

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Salix Investigational Site

Baltimore, Maryland, 21228, United States

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Salix Investigational Site

Chevy Chase, Maryland, 20815, United States

Location

Salix Investigational Site

Hagerstown, Maryland, 21743, United States

Location

Salix Investigational Site

Boston, Massachusetts, 02114, United States

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Salix Investigational Site

Boston, Massachusetts, 02115, United States

Location

Salix Investigational Site

Brockton, Massachusetts, 02302, United States

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Salix Investigational Site

Springfield, Massachusetts, 01105, United States

Location

Salix Investigative Site

Chesterfield, Michigan, 48047, United States

Location

Salix Investigational Site

Wyoming, Michigan, 49519, United States

Location

Salix Investigational Site

Minneapolis, Minnesota, 55455, United States

Location

Salix Investigative Site

Tupelo, Mississippi, 38801, United States

Location

Salix Investigational Site

Kansas City, Missouri, 64131, United States

Location

Salix Investigative Site

St Louis, Missouri, 63110, United States

Location

Salix Investigational Site

Marlton, New Jersey, 08053, United States

Location

Salix Investigational Site

New Brunswick, New Jersey, 07102, United States

Location

Salix Investigative Site

Brooklyn, New York, 60153, United States

Location

Salix Investigational Site

Flushing, New York, 11040, United States

Location

Salix Investigational Site

New York, New York, 10016, United States

Location

Salix Investigational Site

New York, New York, 10032, United States

Location

Salix Investigational Site

Rochester, New York, 14642, United States

Location

Salix Investigative Site

The Bronx, New York, 10467, United States

Location

Salix Investigational Site

Asheville, North Carolina, 28801, United States

Location

Salix Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

Salix Investigative Site

Charlotte, North Carolina, 28204, United States

Location

Salix Investigational Site

Charlotte, North Carolina, 28207, United States

Location

Salix Investigational Site

Fayetteville, North Carolina, 28304, United States

Location

Salix Investigational Site

Wilmington, North Carolina, 28403, United States

Location

Salix Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

Salix Investigative Site

Cincinnati, Ohio, 45224, United States

Location

Salix Investigational Site

Cincinnati, Ohio, 45249, United States

Location

Salix Investigational Site

Cleveland, Ohio, 44195, United States

Location

Salix Investigative Site

Dayton, Ohio, 45415, United States

Location

Salix Investigational Site

Mentor, Ohio, 44060, United States

Location

Salix Investigational Site

Portland, Oregon, 97210, United States

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Salix Investigative Site

Bristol, Tennessee, 37620, United States

Location

Salix Investigational Site

Chattanooga, Tennessee, 37421, United States

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Salix Investigational Site

Nashville, Tennessee, 37205, United States

Location

Salix Investigational Site

Nashville, Tennessee, 37211, United States

Location

Salix Investigative Site

Arlington, Texas, 76012, United States

Location

Salix Investigational Site

Austin, Texas, 78705, United States

Location

Salix Investigational Site

Dallas, Texas, 75203, United States

Location

Salix Investigational Site

Dallas, Texas, 75246, United States

Location

Salix Investigative Site

Dallas, Texas, 75390, United States

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Salix Investigational Site

Fort Worth, Texas, 76104, United States

Location

Salix Investigational Site

Houston, Texas, 77005, United States

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Salix Investigational Site

Houston, Texas, 77030, United States

Location

Salix Investigational Site

Houston, Texas, 77090, United States

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Salix Investigational Site

San Antonio, Texas, 78215, United States

Location

Salix Investigational Site

San Antonio, Texas, 78229, United States

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Salix Investigational Site

Bountiful, Utah, 84010, United States

Location

Salix Investigative Site

Salt Lake City, Utah, 84132, United States

Location

Salix Investigational Site

Charlottesville, Virginia, 22908, United States

Location

Salix Investigative Site

Norfolk, Virginia, 23502, United States

Location

Salix Investigative Site

Richmond, Virginia, 23249, United States

Location

Salix Investigational Site

Richmond, Virginia, 23298, United States

Location

Salix Investigative Site

Richland, Washington, 99352, United States

Location

Salix Investigative Site

Seattle, Washington, 98104, United States

Location

Salix Investigative Site

Krasnogorsk, Russia

Location

Salix Investigative Site

Moscow, Russia

Location

Salix Investigative Site

Novosibirsk, Russia

Location

Salix Investigative Site

Saint Petersburg, Russia

Location

Salix Investigative Site

Samara, Russia

Location

Salix Investigative Site

Smolensk, Russia

Location

Salix Investigative Site

Stavropol, Russia

Location

Related Publications (2)

• Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.

  PMID: 37467180 DERIVED

• 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.

  PMID: 35750249 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Rifaximin; Serine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• James Joffrion

  Bausch Health Americas, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: July 22, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: October 23, 2019

Record last verified: 2019-10

Locations

US (113); RU (7)