Chronic Hepatitis C
Conditions
Keywords
Hepatitis C, Chronic
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 treatment-naive patients.
Interventions
DRUGNitazoxanide
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.
DRUGPlacebo
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.
BIOLOGICALPeginterferon alfa-2a
One weekly injection of 180µg of peginterferon α-2a for 48 weeks.
DRUGRibavirin
Weight-based ribavirin for 48 weeks.
Sponsors
Romark Laboratories L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) | 24 weeks after end of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| End of Treatment Response (HCV RNA Below Lower Limit of Detection) | At end of treatment | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection at the end of treatment. All others were considered non-responders. |
| Early Virologic Response (HCV RNA Below Lower Limit of Detection) | After 12 weeks combination treatment | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 12 weeks of combination therapy. |
| Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) | After 4 weeks combination treatment | Hepatitis C Virus Ribonucleic Acid (HCV RNA) below lower limit of detection after 4 weeks of combination therapy. |
| Changes in ALT | From baseline to week 8 | 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. |
Countries
United States
Participant flow
Recruitment details
This study recruited patients from 13 study centers in the United States, including 2 Veterans Administration hospitals.
Participants by arm
| Arm | Count |
|---|---|
| NTZ+PR 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. | 75 |
| Placebo+PR 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. | 37 |
| Total | 112 |
Baseline characteristics
| Characteristic | Placebo+PR | NTZ+PR | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 74 Participants | 111 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 8 | 50 years STANDARD_DEVIATION 7 | 50 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 37 participants | 75 participants | 112 participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 39 Participants |
| Sex: Female, Male Male | 24 Participants | 49 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 75 | 37 / 37 |
| serious Total, serious adverse events | 12 / 75 | 7 / 37 |
Outcome results
Primary
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.
Time frame: 24 weeks after end of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) | Responders | 32 participants |
| NTZ+PR | Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 43 participants |
| Placebo+PR | Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) | Responders | 13 participants |
| Placebo+PR | Sustained Virologic Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 24 participants |
Secondary
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.
Time frame: From baseline to end of follow up
Population: This analysis was conducted using only data for patients that completed the baseline through the end of follow-up time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Changes in ALT | Remains Elevated | 9 participants |
| NTZ+PR | Changes in ALT | Elevated to Normal | 23 participants |
| NTZ+PR | Changes in ALT | Remains Normal | 13 participants |
| NTZ+PR | Changes in ALT | Normal to Elevated | 0 participants |
| Placebo+PR | Changes in ALT | Normal to Elevated | 1 participants |
| Placebo+PR | Changes in ALT | Remains Elevated | 2 participants |
| Placebo+PR | Changes in ALT | Remains Normal | 8 participants |
| Placebo+PR | Changes in ALT | Elevated to Normal | 7 participants |
Secondary
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.
Time frame: From baseline to week 8
Population: This analysis was conducted using only data for patients that completed the baseline through week 8 time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Changes in ALT | Remains Elevated | 23 participants |
| NTZ+PR | Changes in ALT | Elevated to Normal | 29 participants |
| NTZ+PR | Changes in ALT | Remains Normal | 16 participants |
| NTZ+PR | Changes in ALT | Normal to Elevated | 3 participants |
| Placebo+PR | Changes in ALT | Normal to Elevated | 2 participants |
| Placebo+PR | Changes in ALT | Remains Elevated | 5 participants |
| Placebo+PR | Changes in ALT | Remains Normal | 17 participants |
| Placebo+PR | Changes in ALT | Elevated to Normal | 11 participants |
Secondary
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
Time frame: From baseline to week 16
Population: This analysis was conducted using only data for patients that completed the baseline through week 16 time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Changes in ALT | Remains Elevated | 12 participants |
| NTZ+PR | Changes in ALT | Elevated to Normal | 38 participants |
| NTZ+PR | Changes in ALT | Remains Normal | 17 participants |
| NTZ+PR | Changes in ALT | Normal to Elevated | 1 participants |
| Placebo+PR | Changes in ALT | Normal to Elevated | 1 participants |
| Placebo+PR | Changes in ALT | Remains Elevated | 4 participants |
| Placebo+PR | Changes in ALT | Remains Normal | 15 participants |
| Placebo+PR | Changes in ALT | Elevated to Normal | 11 participants |
Secondary
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.
Time frame: From baseline to end of treatment
Population: This analysis was conducted using only data for patients that completed the baseline through end of treatment time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Changes in ALT | Remains Elevated | 4 participants |
| NTZ+PR | Changes in ALT | Elevated to Normal | 28 participants |
| NTZ+PR | Changes in ALT | Remains Normal | 13 participants |
| NTZ+PR | Changes in ALT | Normal to Elevated | 0 participants |
| Placebo+PR | Changes in ALT | Normal to Elevated | 0 participants |
| Placebo+PR | Changes in ALT | Remains Elevated | 3 participants |
| Placebo+PR | Changes in ALT | Remains Normal | 9 participants |
| Placebo+PR | Changes in ALT | Elevated to Normal | 6 participants |
Secondary
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.
Time frame: After 12 weeks combination treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Early Virologic Response (HCV RNA Below Lower Limit of Detection) | Responders | 45 participants |
| NTZ+PR | Early Virologic Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 30 participants |
| Placebo+PR | Early Virologic Response (HCV RNA Below Lower Limit of Detection) | Responders | 18 participants |
| Placebo+PR | Early Virologic Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 19 participants |
Secondary
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.
Time frame: At end of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | End of Treatment Response (HCV RNA Below Lower Limit of Detection) | Responders | 46 participants |
| NTZ+PR | End of Treatment Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 29 participants |
| Placebo+PR | End of Treatment Response (HCV RNA Below Lower Limit of Detection) | Responders | 18 participants |
| Placebo+PR | End of Treatment Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 19 participants |
Secondary
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.
Time frame: After 4 weeks combination treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTZ+PR | Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) | Responders | 9 participants |
| NTZ+PR | Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 66 participants |
| Placebo+PR | Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) | Responders | 7 participants |
| Placebo+PR | Rapid Virologic Response (HCV RNA Below Lower Limit of Detection) | Non-responders | 30 participants |