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 RnLC2131 is a Phase 2, randomized, double-blind, placebo controlled, multicenter study evaluating the efficacy (prevention of hospitalization for complications of liver cirrhosis or all-cause mortality in subjects with early decompensated liver cirrhosis) and safety of Rifaximin SSD tablets in subjects with early decompensated liver cirrhosis. Subjects who have early decompensated liver cirrhosis as defined by the presence of medically non-refractory ascites who have not previously experienced an episode of hepatic encephalopathy (He), spontaneous bacterial peritonitis (SBP), esophageal variceal bleeding (eVB), or hepatorenal syndrome (HRS) will be enrolled in the study. Subjects will complete a 1 to 21-day Screening Period, a 24-week Treatment Period, and a 2-week Follow-up Period. Subjects who successfully complete the Screening Period will enter the Treatment Period and will be randomized in a 1:1:1:1:1:1 to the following 6 treatment arms. all treatments will be administered once a day at bedtime.
Treatment a: Rifaximin SSD 40 mg qhs (iR Tablet)
Treatment B: Rifaximin SSD 80 mg qhs (iR Tablet)
Treatment C: Rifaximin SSD 40 mg qhs (SeR Tablet)
Treatment D: Rifaximin SSD 80 mg qhs (SeR Tablet)
Treatment e: Rifaximin SSD 80 mg qhs (iR Tablet) + Rifaximin 80 mg qhs (SeR Tablet)
Treatment F: Placebo qhs
1. Subject is >=18 years of age.
2. Subject is male or female.
-Females of childbearing (reproductive) potential must have a negative serum pregnancy test at screening and agree to use an acceptable method of contraception throughout their participation in the study.
3. Subject has a diagnosis of liver cirrhosis and documented ascites, either by imaging study or physical exam (Note: Subjects with Grade 1 ascites are permitted in the study), but has not yet experienced any of the following complications of cirrhosis:
-HE - altered mental status diagnosed as hepatic encephalopathy
-EVB - clinically significant gastrointestinal bleed
-SBP - greater than 250 polymorphonuclear (PMN) cells/mm3 and/or positive monomicrobial culture in the ascitic fluid
-Renal failure in the presence of ascites - rise in the serum creatinine by 0.5 mg/dL (to greater than 1.5 mg/dL), with ascites documented on physical examination, imaging, and/or admitted on diuretics for the treatment of ascites
-Development of medically refractory ascites
4. Subject has a Model End Stage Liver Disease (MELD) score of >= 12.
5. Subject is capable of understanding the requirements of the study, and is willing to comply with all study procedures.
6. Subject understands the language of the informed consent form, and is capable and willing to sign the informed consent form.
7. Subject has close family or other personal contacts that can provide continuing oversight to the subject and will be available to the subject during the conduct of the trial.