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

• Status: Completed
• Trial end date: 2015-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bausch Health Americas, Inc.; Valeant Pharmaceuticals International, Inc.
• Treatments: Rifamycins; Rifaximin

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.