Study of Nitazoxanide, Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Hepatitis C Patients

Study Overview
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Brief Summary
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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 treatment-naive patients.

Official Title
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Phase II, Randomized, Double-blind, Placebo-controlled Study of Nitazoxanide in Combination With Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Patients With Hepatitis C

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Placebo
* Biological: Peginterferon alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis C genotype 1. Exclusion Criteria: Patients that have previously received treatment with any interferon or interferon-based treatment for chronic hepatitis C. 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 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) >34. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>One nitazoxanide 500 mg tablet orally with food twice daily (b.i.d.) for 4 weeks followed by 500 mg nitazoxanide b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks. | Drug: Nitazoxanide<br>* One nitazoxanide 500 mg tablet orally with food twice daily (b.i.d.) for 4 weeks followed by 500 mg nitazoxanide b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks.<br>* Other names: Alinia;Biological: Peginterferon alfa-2a<br>* One weekly injection of 180µg of peginterferon α-2a for 48 weeks.<br>* Other names: PEGASYS;Drug: Ribavirin<br>* Weight-based ribavirin for 48 weeks.<br>* Other names: COPEGUS;|
| Placebo Comparator: 2<br>One placebo tablet orally with food twice daily (b.i.d.) for 4 weeks followed by placebo b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks. | Drug: Placebo<br>* One placebo tablet orally with food twice daily (b.i.d.) for 4 weeks followed by placebo b.i.d. plus one weekly injection of 180µg of peginterferon α-2a plus weight-based ribavirin for 48 weeks.<br>Biological: Peginterferon alfa-2a<br>* One weekly injection of 180µg of peginterferon α-2a for 48 weeks.<br>* Other names: PEGASYS;Drug: Ribavirin<br>* Weight-based ribavirin for 48 weeks.<br>* Other names: COPEGUS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection 24 weeks after the end of treatment. All others were considered non-responders. | 24 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End of Treatment Response (HCV RNA Below Lower Limit of Detection) | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection at the end of treatment. All others were considered non-responders. | At end of treatment | 
| Early Virologic Response (HCV RNA Below Lower Limit of Detection) | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 12 weeks of combination therapy. | After 12 weeks combination treatment | 
| Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 4 weeks of combination therapy. | After 4 weeks combination treatment | 
| Changes in ALT | This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up. | From baseline to week 8 | 
| Changes in ALT | This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up | From baseline to week 16 | 
| Changes in ALT | This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up. | From baseline to end of treatment | 
| Changes in ALT | This analysis was conducted using a comparison of changes in Alanine aminotransferase (ALT) from baseline through week 8, week 16, end of treatment and end of follow up. | From baseline to end of follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Chronic