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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01904409
First received: July 17, 2013
Last updated: February 3, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Liver Cirrhosis
Drug: Placebo
Drug: Rifaximin SSD 40 mg IR tablet
Drug: Rifaximin SSD 80 mg IR tablet
Drug: Rifaximin SSD 40 mg SER tablet
Drug: Rifaximin SSD 80 mg SER tablet
Drug: Rifaximin SSD 80 mg IR tablet + rifaximin SSD 80 mg SER tablet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Salix Pharmaceuticals:

Primary Outcome Measures:
  • Time to all-cause mortality or hospitalization that is attributable to complications of liver disease. [ Time Frame: Weeks 1 through 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Pharmacokinetics of rifaximin and its metabolite. [ Time Frame: Weeks 1 through 24 ] [ Designated as safety issue: No ]
    This outcome will measure the plasma levels of rifaximin and its metabolite (25-desacetyl rifaximin) for each patient during the 24-week treatment period.

  • Incidence of treatment-emergent adverse events. [ Time Frame: Weeks 1 through 24 ] [ Designated as safety issue: Yes ]
    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).

  • Change in clinical laboratory parameters. [ Time Frame: Weeks 1 through 24 ] [ Designated as safety issue: Yes ]
    This outcome will measure the changes in each patient's clinical laboratory test results during the treatment period.

  • Changes in electrocardiogram measurements [ Time Frame: Weeks 1 through 24 ] [ Designated as safety issue: Yes ]
    This outcome will measure the changes in measurements obtained from 12-lead electrocardiograms for each patient during the treatment period.

  • Changes in indices of health outcomes [ Time Frame: Weeks, 4, 8, 12, 16, and 24 ] [ Designated as safety issue: No ]
    This outcome will evaluate each patient's responses on questionnaires that assess health status.


Estimated Enrollment: 420
Study Start Date: June 2013
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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
Experimental: rifaximin SSD 80 mg IR tablet + rifaximin SSD 80 mg SER 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 80 mg IR tablet + rifaximin SSD 80 mg SER tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01904409

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Locations
United States, Alabama
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Dothan, Alabama, United States, 36305
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Mobile, Alabama, United States, 36617
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Tucson, Arizona, United States, 85712
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Sponsors and Collaborators
Salix Pharmaceuticals
Investigators
Study Director: James Joffrion Salix Pharmaceuticals
  More Information

No publications provided

Responsible Party: Salix Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01904409     History of Changes
Other Study ID Numbers: RNLC2131
Study First Received: July 17, 2013
Last Updated: February 3, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Liver Cirrhosis
Digestive System Diseases
Liver Diseases
Rifaximin
Anti-Infective Agents
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015