Influenza
Conditions
Keywords
influenza
Brief summary
This is a randomized clinical trial designed to evaluate the safety/efficacy of two dosing regimens of oral nitazoxanide compared to placebo in the treatment of acute uncomplicated influenza in adults and adolescents. The investigators hypothesize that treatment with Nitazoxanide will reduce the duration of symptoms in patients with confirmed influenza infection. Secondarily, the investigators hypothesize that treatment with nitazoxanide will reduce the complications of influenza, severity of symptoms, time lost from work, time to return to normal daily activities.
Detailed description
A Randomized, Double-Blind, Placebo Controlled Study of Nitazoxanide in Adults and Adolescents with Acute Uncomplicated Influenza. The primary objectives of this study are to demonstrate the efficacy of nitazoxanide administered 300 mg two times per day for 5 days or 600 mg two times per day for 5 days in reducing the time to resolution of all clinical symptoms of influenza. The study will also evaluate pharmacokinetics of nitazoxanide in a subset of 24 patients and the safety of the nitazoxanide regimen compared to a placebo via analysis of adverse events and laboratory safety tests. Blood samples will be collected for all patients at baseline, day 7 and day 28, and for a subset of 24 patients aged 18-65 years (pharmacokinetics subset) on day 2. Urine samples will be collected at baseline and day 7. Nasal swabs will be collected at baseline and day 7 for all patients and on days 2, 3, 4 and 5 for a subset of patients (approximately 20% of patients).
Interventions
DRUGNitazoxanide
Tablets, 300 mg (one 300 mg tablet + 1 placebo tablet) with food twice daily for 5 days
DRUGPlacebo
Tablets, (2 tablets) twice daily with food for 5 days
Sponsors
Romark Laboratories L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* age 12 to 65 years * Presence of clinical signs, respiratory symptoms and constitutional symptoms compatible with influenza infection: 1. fever, 2. at least one of the following respiratory symptoms: cough, sore throat, nasal discharge, nasal congestion, sneezing. 3. At least one of the following constitutional symptoms: headache, myalgia, seats, chills, fatigue of any severity (mild, moderate, severe) * Confirmation of Influenza A or B infection in the local community * Onset of illness no more than 48 hours before presentation. Time of onset of illness is defined as either the earlier of (1) the time when the temperature was first measured as elevated, or (2) the time when the patient experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom. * willing and able to comply with protocol requirements and provide informed consent
Exclusion criteria
* severity of illness requiring or anticipated to require in-hospital care * High risk of complications from influenza as follows: 1. persons with asthma or other chronic pulmonary diseases 2. persons with hemodynamically significant cardiac disease 3. persons who have immunosuppressive disorders or receiving immunosuppressive therapy 4. persons infected with Human Immunodeficiency Virus (HIV) 5. persons with sickle cell anemia or other hemoglobinopathies 6. persons with diseases requiring long-term aspirin therapy 7. persons with chronic renal dysfunction 8. persons with liver disorders 9. Persons with cancer 10. Persons with chronic metabolic disease such as diabetes and inherited mitochondrial disorders 11. Persons with neuromuscular disorders, seizure disorders, or cognitive dysfunction 12. Residents of any age of nursing homes or long-term institutions. * Females of child bearing age who are pregnant, breastfeeding or sexually active without birth control * vaccination for influenza or H1N1 (Swine Flu) on or after August 1, 2010 * treatment with antiviral medication such as oseltamivir, zanamivir, amantadine, or rimantadine within 30 days of screening. * Prior treatment with nitazoxanide within 30 days prior to screening. * subjects with active respiratory allergies or expected to require anti-allergy medications during the study period. * known sensitivity to nitazoxanide * subjects unable to take oral medication * subjects with chronic kidney or liver disease * Presence of any other pre-existing chronic infection that is undergoing or requiring medical therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects | Up to 28 days | The primary efficacy analysis for this study was to demonstrate the efficacy of Nitazoxanide (NTZ) administered as 300 mg b.i.d. for 5 days or 600 mg b.i.d. for 5 days in reducing the time to resolution of all clinical symptoms of influenza in patients with laboratory confirmed influenza infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | 7 days | Change in viral titer presented as logarithm with base 10 (log10) 50% Tissue Culture Infective Dose (TCID50) |
| Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | 7 days | Change in viral titer logarithm with base 10 (log10) Ribonucleic Acid (RNA)copies |
| Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50) | 28 days | Median time in hours |
| Time to Return to Normal Daily Activities | 28 days | Time in hours as reported by patient |
| Symptom Severity Score Hours | 28 days | Sum of the symptom severity score hours from first dose to resolution of symptoms. Patients rated each symptom's severity on a score from 0 to 3 (0=absent, 1=mild, 2=moderate, 3=severe). Total symptom severity score hours were calculated by multiplying the sum of the severity scores by duration of symptoms. |
| Time Loss From Work | 28 days | Time loss from work |
| Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | at least 28 days | Time in hours (Median and Interquartile range) |
| Influenza Antibody Response Titer Change: Influenza A 2009 H1N1 | 28 days | change in influenza antibody titer for Influenza A 2009 H1N1 |
| Influenza Antibody Response: Influenza A H3N2 | 28 days | Change in antibody titer for Influenza A H3N2 |
| Influenza Antibody Response: Influenza B | 28 days | Change in antibody titer for Influenza B |
| Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | 28 days | Proportion of patients seroprotected or seroconverted at day 28 |
| Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | 28 days | Proportion of patients seroprotected and seroconverted at day 28 |
| Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | 28 days | Proportion of patients seroprotected and seroconverted at day 28 |
| Complications of Influenza | 28 days | Proportion of patients with a complication of influenza during the course of the study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nitazoxanide 300mg 300 mg nitazoxanide twice daily with food for 5 days | 201 |
| Placebo placebo tablet twice daily with food for 5 days | 212 |
| Nitazoxanide 600mg 2X 300 mg controlled release tablet twice daily with food for five days | 211 |
| Total | 624 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 | 2 |
| Overall Study | Lost to Follow-up | 6 | 7 | 5 |
| Overall Study | Protocol Violation | 1 | 1 | 2 |
| Overall Study | Randomized in error | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Nitazoxanide 600mg | Nitazoxanide 300mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 21 Participants | 20 Participants | 25 Participants | 66 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 189 Participants | 188 Participants | 176 Participants | 553 Participants |
| Age, Continuous | 31 years STANDARD_DEVIATION 13.3 | 32 years STANDARD_DEVIATION 13.2 | 31 years STANDARD_DEVIATION 12.6 | 31 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 212 participants | 211 participants | 201 participants | 624 participants |
| Sex: Female, Male Female | 122 Participants | 129 Participants | 104 Participants | 355 Participants |
| Sex: Female, Male Male | 90 Participants | 82 Participants | 97 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 201 | 7 / 212 | 25 / 211 |
| serious Total, serious adverse events | 0 / 201 | 1 / 212 | 1 / 211 |
Outcome results
Primary
Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects
The primary efficacy analysis for this study was to demonstrate the efficacy of Nitazoxanide (NTZ) administered as 300 mg b.i.d. for 5 days or 600 mg b.i.d. for 5 days in reducing the time to resolution of all clinical symptoms of influenza in patients with laboratory confirmed influenza infection
Time frame: Up to 28 days
Population: 624 patients were enrolled based on inclusion/exclusion criteria. The primary efficacy analysis was conducted on the 257 patients with laboratory confirmed influenza.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide 300mg | Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects | 109.1 Hours |
| Placebo | Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects | 116.7 Hours |
| Nitazoxanide 600mg | Time to Resolution of All Clinical Symptoms of Influenza as Reported by the Subjects | 95.5 Hours |
Secondary
Complications of Influenza
Proportion of patients with a complication of influenza during the course of the study
Time frame: 28 days
Population: All patients who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nitazoxanide 300mg | Complications of Influenza | Otitis | 3 Participants |
| Nitazoxanide 300mg | Complications of Influenza | Pleurisy | 0 Participants |
| Nitazoxanide 300mg | Complications of Influenza | Bronchitis | 10 Participants |
| Nitazoxanide 300mg | Complications of Influenza | Sinusitis | 6 Participants |
| Nitazoxanide 300mg | Complications of Influenza | Pneumonia | 1 Participants |
| Placebo | Complications of Influenza | Sinusitis | 6 Participants |
| Placebo | Complications of Influenza | Bronchitis | 3 Participants |
| Placebo | Complications of Influenza | Pneumonia | 2 Participants |
| Placebo | Complications of Influenza | Otitis | 3 Participants |
| Placebo | Complications of Influenza | Pleurisy | 1 Participants |
| Nitazoxanide 600mg | Complications of Influenza | Otitis | 1 Participants |
| Nitazoxanide 600mg | Complications of Influenza | Pleurisy | 0 Participants |
| Nitazoxanide 600mg | Complications of Influenza | Sinusitis | 2 Participants |
| Nitazoxanide 600mg | Complications of Influenza | Pneumonia | 1 Participants |
| Nitazoxanide 600mg | Complications of Influenza | Bronchitis | 7 Participants |
Secondary
Influenza Antibody Response: Influenza A H3N2
Change in antibody titer for Influenza A H3N2
Time frame: 28 days
Population: Members of the intensive virologic follow up group with laboratory confirmed influenza A H3N2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide 300mg | Influenza Antibody Response: Influenza A H3N2 | 8 Fold change in antibody titer |
| Placebo | Influenza Antibody Response: Influenza A H3N2 | 16 Fold change in antibody titer |
| Nitazoxanide 600mg | Influenza Antibody Response: Influenza A H3N2 | 16 Fold change in antibody titer |
Secondary
Influenza Antibody Response: Influenza B
Change in antibody titer for Influenza B
Time frame: 28 days
Population: Members of intensive virologic follow up group with laboratory confirmed Influenza B
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide 300mg | Influenza Antibody Response: Influenza B | 4 Fold change in antibody titer |
| Placebo | Influenza Antibody Response: Influenza B | 3 Fold change in antibody titer |
| Nitazoxanide 600mg | Influenza Antibody Response: Influenza B | 4 Fold change in antibody titer |
Secondary
Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B
Proportion of patients seroprotected and seroconverted at day 28
Time frame: 28 days
Population: Members of intensive virologic follow up group with laboratory confirmed Influenza B
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nitazoxanide 300mg | Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | Seroprotected at day 28 | 14 Participants |
| Nitazoxanide 300mg | Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | Seroconverted at day 28 | 12 Participants |
| Placebo | Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | Seroprotected at day 28 | 13 Participants |
| Placebo | Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | Seroconverted at day 28 | 10 Participants |
| Nitazoxanide 600mg | Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | Seroprotected at day 28 | 13 Participants |
| Nitazoxanide 600mg | Influenza Antibody Response: Seroprotection and Seroconversion for Influenza B | Seroconverted at day 28 | 13 Participants |
Secondary
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1
Proportion of patients seroprotected or seroconverted at day 28
Time frame: 28 days
Population: Members of intensive virologic follow up group with laboratory confirmed Influenza A 2009 H1N1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nitazoxanide 300mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | Seroprotected at day 28 | 11 Participants |
| Nitazoxanide 300mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | Seroconverted at day 28 | 11 Participants |
| Placebo | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | Seroprotected at day 28 | 14 Participants |
| Placebo | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | Seroconverted at day 28 | 12 Participants |
| Nitazoxanide 600mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | Seroprotected at day 28 | 12 Participants |
| Nitazoxanide 600mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A 2009 H1N1 | Seroconverted at day 28 | 11 Participants |
Secondary
Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2
Proportion of patients seroprotected and seroconverted at day 28
Time frame: 28 days
Population: Members of intensive virologic follow up group with laboratory confirmed Influenza A H3N2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nitazoxanide 300mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | Seroprotected at day 28 | 14 Participants |
| Nitazoxanide 300mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | Seroconverted at day 28 | 13 Participants |
| Placebo | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | Seroprotected at day 28 | 12 Participants |
| Placebo | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | Seroconverted at day 28 | 12 Participants |
| Nitazoxanide 600mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | Seroprotected at day 28 | 12 Participants |
| Nitazoxanide 600mg | Influenza Antibody Response: Seroprotection and Seroconversion for Patients With Influenza A H3N2 | Seroconverted at day 28 | 12 Participants |
Secondary
Influenza Antibody Response Titer Change: Influenza A 2009 H1N1
change in influenza antibody titer for Influenza A 2009 H1N1
Time frame: 28 days
Population: Member of the intensive virologic follow up group with laboratory confirmed Influenza A 2009 H1N1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide 300mg | Influenza Antibody Response Titer Change: Influenza A 2009 H1N1 | 2 Fold change in antibody titer |
| Placebo | Influenza Antibody Response Titer Change: Influenza A 2009 H1N1 | 2 Fold change in antibody titer |
| Nitazoxanide 600mg | Influenza Antibody Response Titer Change: Influenza A 2009 H1N1 | 2 Fold change in antibody titer |
Secondary
Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline
Change in viral titer logarithm with base 10 (log10) Ribonucleic Acid (RNA)copies
Time frame: 7 days
Population: Analysis conducted on 113 patients from the intensive virologic follow up group with laboratory confirmed influenza
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitazoxanide 300mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 5 | -2.42 LOG10 RNA copies | Standard Deviation 1.5 |
| Nitazoxanide 300mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 4 | -1.75 LOG10 RNA copies | Standard Deviation 1.5 |
| Nitazoxanide 300mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 2 | -0.63 LOG10 RNA copies | Standard Deviation 1.4 |
| Nitazoxanide 300mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 3 | -1.34 LOG10 RNA copies | Standard Deviation 1.4 |
| Nitazoxanide 300mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 7 | -2.97 LOG10 RNA copies | Standard Deviation 1.3 |
| Placebo | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 4 | -1.63 LOG10 RNA copies | Standard Deviation 1.8 |
| Placebo | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 2 | -0.22 LOG10 RNA copies | Standard Deviation 1.7 |
| Placebo | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 3 | -0.92 LOG10 RNA copies | Standard Deviation 2 |
| Placebo | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 5 | -2.49 LOG10 RNA copies | Standard Deviation 1.7 |
| Placebo | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 7 | -2.82 LOG10 RNA copies | Standard Deviation 1.6 |
| Nitazoxanide 600mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 7 | -3.08 LOG10 RNA copies | Standard Deviation 1.3 |
| Nitazoxanide 600mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 5 | -2.44 LOG10 RNA copies | Standard Deviation 1.4 |
| Nitazoxanide 600mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 2 | -0.73 LOG10 RNA copies | Standard Deviation 1.5 |
| Nitazoxanide 600mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 4 | -2.21 LOG10 RNA copies | Standard Deviation 1.4 |
| Nitazoxanide 600mg | Mean Change in RT-PCR (Reverse Transcription Polymerase Chain Reaction) Viral Titer From Baseline | Day 3 | -1.64 LOG10 RNA copies | Standard Deviation 1.7 |
Secondary
Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline
Change in viral titer presented as logarithm with base 10 (log10) 50% Tissue Culture Infective Dose (TCID50)
Time frame: 7 days
Population: Analysis conducted on 113 patients from intensive virologic follow up group with laboratory confirmed influenza
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitazoxanide 300mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 5 | -2.46 LOG10 Titer | Standard Deviation 1.8 |
| Nitazoxanide 300mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 4 | -1.86 LOG10 Titer | Standard Deviation 1.9 |
| Nitazoxanide 300mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 2 | -0.58 LOG10 Titer | Standard Deviation 1.4 |
| Nitazoxanide 300mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 3 | -1.26 LOG10 Titer | Standard Deviation 1.8 |
| Nitazoxanide 300mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 7 | -2.82 LOG10 Titer | Standard Deviation 1.6 |
| Placebo | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 4 | -1.65 LOG10 Titer | Standard Deviation 1.9 |
| Placebo | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 2 | -0.03 LOG10 Titer | Standard Deviation 1.7 |
| Placebo | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 3 | -1.21 LOG10 Titer | Standard Deviation 2.2 |
| Placebo | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 5 | -2.41 LOG10 Titer | Standard Deviation 1.8 |
| Placebo | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 7 | -2.79 LOG10 Titer | Standard Deviation 1.8 |
| Nitazoxanide 600mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 7 | -3.01 LOG10 Titer | Standard Deviation 1.4 |
| Nitazoxanide 600mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 5 | -2.55 LOG10 Titer | Standard Deviation 1.4 |
| Nitazoxanide 600mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 2 | -1.11 LOG10 Titer | Standard Deviation 1.7 |
| Nitazoxanide 600mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 4 | -2.58 LOG10 Titer | Standard Deviation 1.3 |
| Nitazoxanide 600mg | Mean Change (Standard Deviation)in 50% Tissue Culture Infective Dose (TCID50) Viral Titer From Baseline | Day 3 | -1.84 LOG10 Titer | Standard Deviation 1.7 |
Secondary
Symptom Severity Score Hours
Sum of the symptom severity score hours from first dose to resolution of symptoms. Patients rated each symptom's severity on a score from 0 to 3 (0=absent, 1=mild, 2=moderate, 3=severe). Total symptom severity score hours were calculated by multiplying the sum of the severity scores by duration of symptoms.
Time frame: 28 days
Population: Analysis conducted for 257 patients with laboratory confirmed influenza
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitazoxanide 300mg | Symptom Severity Score Hours | 1035.1 symptom score *hour | Standard Deviation 765 |
| Placebo | Symptom Severity Score Hours | 1220.9 symptom score *hour | Standard Deviation 592 |
| Nitazoxanide 600mg | Symptom Severity Score Hours | 1125.2 symptom score *hour | Standard Deviation 681 |
Secondary
Time Loss From Work
Time loss from work
Time frame: 28 days
Population: Analysis conducted on 241 patients with laboratory confirmed influenza excluding those who are unemployed
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Nitazoxanide 300mg | Time Loss From Work | 2.6 days |
| Placebo | Time Loss From Work | 3.0 days |
| Nitazoxanide 600mg | Time Loss From Work | 3.3 days |
Secondary
Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50)
Median time in hours
Time frame: 28 days
Population: Analysis performed on 107 patients from the intensive virologic follow up population with laboratory confirmed influenza
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide 300mg | Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50) | 77.0 Hours |
| Placebo | Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50) | 91.3 Hours |
| Nitazoxanide 600mg | Time to Cessation of Viral Shedding Measure by 50% Tissue Culture Infective Dose (TCID50) | 71.8 Hours |
Secondary
Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects
Time in hours (Median and Interquartile range)
Time frame: at least 28 days
Population: 624 patients were enrolled based on inclusion/exclusion criteria. Secondary efficacy analyses were conducted on the 257 patients with laboratory confirmed influenza.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Cough | 96 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Fever | 36 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Myalgia | 46 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Headache | 42 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Nasal Congestion | 84 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Sweats / Chills | 36 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Sore Throat | 63 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Runny Nose | 48 Hours |
| Nitazoxanide 300mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Fatigue | 65 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Headache | 48 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Nasal Congestion | 81 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Runny Nose | 42 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Sore Throat | 52 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Cough | 104 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Myalgia | 46 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Fatigue | 69 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Sweats / Chills | 36 Hours |
| Placebo | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Fever | 31 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Sore Throat | 50 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Nasal Congestion | 60 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Fatigue | 60 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Runny Nose | 43 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Fever | 36 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Headache | 39 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Cough | 84 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Sweats / Chills | 36 Hours |
| Nitazoxanide 600mg | Time to Resolution of Each Individual Symptom of Influenza as Reported by the Subjects | Myalgia | 42 Hours |
Secondary
Time to Return to Normal Daily Activities
Time in hours as reported by patient
Time frame: 28 days
Population: Analysis conducted on 257 patients with laboratory confirmed influenza
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide 300mg | Time to Return to Normal Daily Activities | 84.2 Hours |
| Placebo | Time to Return to Normal Daily Activities | 82.1 Hours |
| Nitazoxanide 600mg | Time to Return to Normal Daily Activities | 84.0 Hours |