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”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2009

Intervention(s) in this Clinical Trial

• Drug: Nitazoxanide
  • One oral 500 mg nitazoxanide tablet twice daily for 52 weeks.
• Drug: Placebo
  • One oral placebo tablet twice daily for 52 weeks.
• Biological: Peginterferon alfa-2a
  • Weekly injections of 180µg peginterferon alfa-2a for 48 weeks.
• Drug: Ribavirin
  • 1000 mg (if <75 kg body weight) or 1200 mg (if ≥75 kg body weight) ribavirin in divided daily doses for 48 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Oral 500 mg nitazoxanide twice daily for 4 weeks followed by oral 500 mg nitazoxanide twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.
• Placebo Comparator: 2
  • Oral placebo twice daily for 4 weeks followed by oral placebo twice daily plus weekly injections of peginterferon alfa-2a plus oral ribavirin (1000 mg if <75 kg body weight or 1200 mg if ≥75 kg body weight) in daily divided doses for 48 weeks.

Primary Measures

• Sustained virologic response (HCV RNA below lower limit of detection)
  • Time Frame: 24 weeks after end of treatment
    Safety Issue?: No

Secondary Measures

• End of treatment response (HCV RNA below lower limit of detection)
  • Time Frame: At end of treatment
    Safety Issue?: No
• Early virologic response (HCV RNA below lower limit of detection)
  • Time Frame: After 12 weeks combination treatment
    Safety Issue?: No
• Rapid virologic response (HCV RNA below lower limit of detection)
  • Time Frame: After 4 weeks combination treatment
    Safety Issue?: No
• Changes in ALT
  • Time Frame: From baseline to weeks 8, 16, end of treatment and end of follow-up
    Safety Issue?: No

Inclusion Criteria:

• Chronic hepatitis C genotype 1.
• Failed to respond to ≥12 weeks of peginterferon and ribavirin (<2 log10 drop in HCV
• RNA at week 12 or detectable 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-HAV IgM Ab, HBsAg, anti-HBc IgM Ab or anti-HIV Ab.
• Decompensated cirrhosis, history of variceal bleeding, ascites, hepatic encephalopathy, CTP score >6 or 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 ULN.
• Hypothyroidism or hyperthyroidism not effectively treated with medication.
• HgbA1c >7.5 or history of diabetes mellitus.
• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Romark Laboratories L.C.

Overall Clinical Trial Officials and Contacts

David Nelson, MD Principal Investigator University of Florida Hepatology  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00495391

Study ID Number: RM01-2025

ClinicalTrials.gov Identifier: NCT00495391

Health Authority: United States: Food and Drug Administration