RNLC2131

Overview

Status: Recruiting
Keywords: PBC
IRB Number: 00066519
Specialty: Gastroenterology
Sub Specialties: Hepatology

Brief Summary

The primary objective of this study is to assess the efficacy of Rifaximin SSD versus placebo in preventing initial complications of liver cirrhosis and all-cause mortality in subjects with liver cirrhosis.

The secondary objectives of this study in subjects with compensated liver cirrhosis are to:

• Assess the safety of Rifaximin SSD following a 24-week treatment regimen
• Assess the population pharmacokinetics of Rifaximin SSD
• Characterize the gastrointestinal microbiota from stool samples, and antibiotic resistance from bacteria cultured from stool samples before and after treatment with Rifaximin SSD
• Assess the effects of treatment with Rifaximin SSD on biological markers of liver cirrhosis
• Assess the effects of treatment with Rifaximin SSD on liver-cirrhosis-related infections

Principal Investigator: Terry Box
Department: Gastroenterology
Co Investigator: Juan Gallegos-Orozco

Contact Information

Name:Tiffany Tomkinson
Phone: 801-585-9155
Email: tiffany.tomkinson@hsc.utah.edu

Inclusion Criteria

Inclusion Criteria
A subject will be eligible for inclusion in this study if he/she meets all of the following criteria:
1. Subject is greater than, or equal to, 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. Acceptable methods of contraception include double barrier methods (condom with
spermicidal jelly or a diaphragm with spermicide), hormonal methods (eg, oral contraceptives,
patches or medroxyprogesterone acetate), or an intrauterine device (IUD) with a documented
failure rate of less than 1% per year. Abstinence or partner(s) with a vasectomy may be considered
an acceptable method of contraception at the discretion of the investigator.
Note: Females who have been surgically sterilized (eg, hysterectomy or bilateral tubal ligation) or
who are postmenopausal (total cessation of menses for > 1 year) will not be considered “females of
childbearing potential”.
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.

Exclusion Criteria

Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Current or Past Medical History
1. Subject has history of a major psychiatric disorder including uncontrolled major depression or
controlled or uncontrolled psychoses within the past 24 months prior to signing the informed consent
(Diagnostic and Statistical Manual of Mental Disorders, 4th.) that in the opinion of the investigator
would prevent completion of the study, interfere with analysis of study results, or negatively impact
the subject’s participation in the study.
2. Subject has history of alcohol abuse or substance abuse within the past 3 months prior to signing the
informed consent (Diagnostic and Statistical Manual of Mental Disorders, 4th.)
3. Subject has documented cholestatic liver disease such as primary sclerosing cholangitis or primary
biliary sclerosis.
4. Subject has had prophylactic variceal banding or is scheduled to undergo prophylactic banding
within 30 days of randomization.
5. Subject has been diagnosed with an infection for which they are currently taking oral or parenteral
antibiotics.
6. Subject has significant hypovolemia, or any electrolyte abnormality that can affect mental function
(eg, serum sodium < 125 mEq/L, serum calcium > 10 mg/dL).
7. Subject has severe hypokalemia as defined by a serum potassium concentration < 2.5 mEq/L.
8. Subject is anemic, as defined by a hemoglobin concentration of ≤ 8 g/dL.
9. Subject has renal insufficiency with a creatinine of ≥ 1.5 mg/dL.
Note: Laboratory tests related to Inclusion/Exclusion criteria can be repeated once, before
considering subject as a Screening Failure (given all other Inclusion/Exclusion criteria are met/notmet
respectively) at the discretion of the Investigator.
10. Subject shows presence of intestinal obstruction or has inflammatory bowel disease.
11. Subject has uncontrolled Type 1 or Type 2 diabetes, or diabetes requiring insulin. Note: Subjects
with controlled diabetes may be enrolled if they are on stable doses of oral hypoglycemic drugs for at
least 3-months prior to randomization, and demonstrate clinically acceptable blood glucose control
within 30 days of randomization in the opinion of the investigator.12. Subject has a history of seizure disorders.
13. Subject has 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 randomization.
14. Subject has an 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).
15. Subject has hepatocellular carcinoma (HCC). Note: Alpha-fetoprotein (AFP) concentration will be
measured at screening. If the AFP is greater than 200 ng/mL, the subject is excluded from
participation in the study. If the AFP is above the upper limit of normal and
≤ 200 ng/mL, cross-sectional imaging techniques should be used to rule out HCC.
16. Subject has any condition or circumstance that adversely affects the subject or could cause
noncompliance with treatment or visits, may affect the interpretation of clinical data, or may
otherwise contraindicate the subject’s participation in the study.
17. If female, subject is pregnant or at risk of pregnancy, or is lactating.
Infections
18. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of randomization.
19. Known human immunodeficiency virus (HIV) infection.
20. Subject has a positive stool test for Yersinia enterocolitica, Campylobacter jejuni, Salmonella,
Shigella, ovum and parasites, and/or Clostridium difficile (C. difficile). NOTE: Results of stool tests
must be confirmed as negative prior to randomization.
21. Subject has a history of tuberculosis infection and/or has received treatment for a tuberculosis
infection. If subject has had a previous positive skin test for tuberculosis antigen then they must
have a current negative chest X-ray to be eligible and must not have received previous treatment.
General/Compliance
22. Subject is an employee of the site that is directly involved in the management, administration, or
support of this study or is an immediate family member of the same.
23. Subject has a history of hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or
any of the components of Rifaximin SSD.
24. Subject used any investigational product or device, or participated in another research study within
30 days prior to randomization.