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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Salix Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Salix Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01904409
First received: July 17, 2013
Last updated: February 7, 2014
Last verified: February 2014

July 17, 2013
February 7, 2014
June 2013
July 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01904409 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Dose-ranging Study of Rifaximin Soluble Solid Dispersion (SSD) Tablets for the Prevention of Complications of Early Decompensated Liver Cirrhosis
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
  • Placebo Comparator: Placebo
    Placebo tablets once daily.
    Intervention: Drug: Placebo
  • Experimental: Rifaximin SSD 40 mg IR tablet
    Rifaximin soluble solid dispersion (SSD) 40 mg immediate release (IR) tablet once daily.
    Intervention: 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.
    Intervention: 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.
    Intervention: 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.
    Intervention: 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.
    Intervention: Drug: Rifaximin SSD 80 mg IR tablet + rifaximin SSD 80 mg SER tablet
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
420
Not Provided
July 2014   (final data collection date for primary outcome measure)

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).
  • Has 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.
Both
18 Years and older
No
Contact: Katie Gregg 919-862-1063 katie.gregg@salix.com
United States
 
NCT01904409
RNLC2131
Yes
Salix Pharmaceuticals
Salix Pharmaceuticals
Not Provided
Study Director: Enoch Bortey Salix Pharmaceuticals
Salix Pharmaceuticals
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP