Clinical trial NCT00495391: Study of Nitazoxanide, Peginterferon Alfa-2a and Ribavirin for the Treatment of Hepatitis C
Official title: Phase II, Randomized, Double-blind, Placebo-controlled Study of Nitazoxanide in Combination With Peginterferon Alfa-2a and Ribavirin in Patients With Hepatitis C Who Have Failed to Respond to a Prior Course of Peginterferon and Ribavirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C, Chronic
Lead sponsor: Romark Laboratories L.C.
Sponsor class: INDUSTRY
First posted: 2007-07-03
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if nitazoxanide in combination with peginterferon alfa-2a and ribavirin is safe and effective in treating chronic hepatitis C in patients that have previously failed to respond to treatment with peginterferon and ribavirin.


Eligibility criteria: Inclusion Criteria:

* Chronic hepatitis C genotype 1.
* Failed to respond to ≥12 weeks of peginterferon and ribavirin (\<2 log10 drop in Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 12 or detectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at week 24).

Exclusion Criteria:

* Females of child-bearing age who are either pregnant, breast-feeding or not using birth control and are sexually active.
* Males whose female partners are either pregnant or of child-bearing potential or not using birth control and are sexually active.
* Other causes of liver disease including autoimmune hepatitis.
* Transplant recipients receiving immune suppression therapy.
* Screening tests positive for Anti-Hepatitis A Virus Immunoglobulin M Antibody (anti-HAV IgM Ab), Hepatitis B's antigen (HBsAg), Anti-Hepatitis B core antigen Immunoglobulin M Antibody (anti-HBc IgM Ab) or Anti-Human Immunodeficiency Virus Antibody (anti-HIV Ab).
* Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, Child-Turcotte-Pugh (CTP) score \>6 or Model for End-stage Liver Disease (MELD) score \>8.
* Alcohol consumption of \>40 grams per day or an alcohol use pattern that will interfere with the study.
* Absolute neutrophil count \<1500 cells/mm3; platelet count \<135,000 cells/mm3; hemoglobin \<12 g/dL for women and \<13 g/dL for men; or serum creatinine concentration ≥1.5 times Upper Limit of Normal (ULN).
* Hypothyroidism or hyperthyroidism not effectively treated with medication.
* Hemoglobin A1C (HgbA1c) \>7.5 or history of diabetes mellitus.
* Body Mass Index (BMI) \>28.
* History or other clinical evidence of significant or unstable cardiac disease.
* History or other clinical evidence of chronic pulmonary disease associated with functional impairment.
* Serious or severe bacterial infection(s).
* Ulcerative or hemorrhagic/ischemic colitis.
* Pancreatitis.
* History of severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization.
* History of uncontrolled severe seizure disorder.
* Requires concomitant theophylline or methadone.
* History of immunologically mediated disease requiring more than intermittent anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids.
* History or other evidence of severe retinopathy or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension.
* Hemoglobinopathies.
* History of hypersensitivity or intolerance to nitazoxanide or any of the excipients comprising the nitazoxanide tablets, peginterferon alfa-2a injectable solution or ribavirin tablets.

Primary outcomes:
measure: Sustained Virologic Response (HCV RNA Below Lower Limit of Detection)
timeFrame: 24 weeks after end of treatment
Secondary outcomes:
measure: End of Treatment Response (HCV RNA Below Lower Limit of Detection)
timeFrame: At end of treatment
measure: Early Virologic Response (HCV RNA Below Lower Limit of Detection)
timeFrame: After 12 weeks combination treatment
measure: Rapid Virologic Response (HCV RNA Below Lower Limit of Detection)
timeFrame: After 4 weeks combination treatment
measure: Changes in ALT
timeFrame: From baseline to week 8
measure: Changes in ALT
timeFrame: From baseline to week 16
measure: Changes in ALT
timeFrame: From baseline to end of treatment
measure: Changes in ALT
timeFrame: From baseline to end of follow up
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Healthcare System
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: New Haven
country: United States
facility: Yale University Digestive Diseases
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Hepatology
state: Florida
city: Largo
country: United States
facility: Florida Center for Gastroenterology
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
Study officials:
affiliation: University of Florida Hepatology
name: David Nelson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brooke Army Medical Center
name: Stephen Harrison, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida Center for Gastroenterology
name: Arthur Berman, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Nashville Medical Research Institute
name: Ronald Pruitt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Ahmed Aijaz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Palo Alto Health Care System
name: Ramsey Cheung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Ira Jacobson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGuire VA Medical Center
name: Mitchell Shiffman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University Digestive Diseases
name: Joseph Lim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Atlanta Gastroenterology Associates
name: Norman Gitlin, MD
role: PRINCIPAL_INVESTIGATOR
References: