Enterovirus, Rhinovirus
Conditions
Keywords
Enterovirus, Rhinovirus
Brief summary
Trial to evaluate efficacy and safety of nitazoxanide in the treatment of colds due to Enterovirus/Rhinovirus infection
Detailed description
Multicenter, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety of nitazoxanide in the treatment of colds due to Enterovirus/Rhinovirus infection
Interventions
DRUGNitazoxanide
Nitazoxanide 600 mg administered orally twice daily for five days
DRUGPlacebo
Placebo administered orally twice daily for five 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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects at least 12 years of age 2. Presence of clinical signs and/or symptoms consistent with an acute illness compatible with EV/RV infection (each of the following is required): 1. Presence of moderate or severe rhinorrhea defined as attempting to relieve nasal symptoms by blowing, wiping, or sniffling at least twice per hour for any one hour within 12 hours preceding study entry, AND 2. Presence of cough, sore throat or nasal obstruction. 3. Negative rapid influenza diagnostic test (required only if the subject has an oral temperature \>100°F in the clinic or if the latest CDC weekly influenza report shows influenza prevalence Regional or higher for the institution's state). A result from a rapid influenza diagnostic test performed on the same day that informed consent is obtained will be sufficient to meet this criterion if documentation of test results is available as part of medical history. 4. Onset of illness no more than 40 hours before enrollment in the trial. Onset of illness is defined as the first time at which the subject experienced rhinorrhea, cough, sore throat or nasal obstruction. 5. Willing and able to provide written informed consent (including assent by legal guardian if under 18 years of age) and comply with the requirements of the protocol, including completion of the subject diary
Exclusion criteria
1. Persons requiring or anticipated to require in-hospital care 2. Cystic fibrosis 3. Cardiac arrhythmia 4. Immunologic disorders or receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants, immunomodulatory therapies for certain autoimmune diseases) 5. Untreated HIV infection or treated HIV infection with a CD4 count below 350 cells/mm3 in the last 6 months 6. Persons with sickle cell anemia or other hemoglobinopathies 7. Poorly controlled insulin-dependent diabetes mellitus (HbA1C \>8.0%) 8. Concurrent infection at the screening examination that requires systemic antimicrobial therapy 9. Females of childbearing potential who are either pregnant or sexually active without the use of birth control. Female subjects of child-bearing potential that are sexually active must have a negative baseline pregnancy test and must agree to continue an acceptable method of birth control for the duration of the study and for 1 month post-treatment. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an IUD, or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. Female subjects are considered of childbearing potential unless they are postmenopausal (absence of menstrual bleeding for 1 year - or 6 months if laboratory confirmation of hormonal status), or have had a hysterectomy, bilateral tubular ligation or bilateral oophorectomy. 10. Females who are breastfeeding 11. Receipt of any dose of NTZ within 30 days prior to screening 12. Prior treatment with any investigational drug therapy within 30 days prior to screening 13. Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies 14. Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets 15. Subjects unable to take oral medications 16. Subjects who, in the judgment of the Investigator, will be unlikely to comply with the requirements of this protocol including completion of the subject diary
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint) | Up to 21 days | Subjects used the FLU-PRO questionnaire once daily in the evening to score the severity of 32 FLU-PRO symptoms. Symptom response was deemed achieved when the rating for each of the 32 FLU-PRO symptoms was ≤ its assigned threshold for 2 consecutive daily diary periods without use of symptom relief medication. The symptom response thresholds were developed by applying an algorithm to blinded symptoms data to select the set of 32 symptom thresholds most closely associated with patient-reported usual health. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From First Dose to Ability to Perform All Normal Activities | Up to 21 days | Subjects completed a diary including rating ability to perform normal activities on a scale from 0 (able to perform no normal activities) to 10 (able to perform all normal activities) daily in the evening. The time from first dose to ability to perform all normal activities is the time in hours between the first dose of study medication and that time when the subject first reported a score of 10 (able to perform all normal activities) for two consecutive daily diary periods without use of symptom relief medication. |
| Proportions Experiencing Complications of EV/RV Infection | 28 days | Complications of colds due to EV/RV infection include pneumonia, otitis media, bronchitis, sinusitis, exacerbations of asthma or COPD, worsening of pre-existing health conditions, secondary infections requiring systemic antibiotic use, hospitalization due to cold or complications of the cold, and death due to cold or complications of the cold. Proportions experiencing complications of EV/RV infection were compared across treatment groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Return to Usual Health | 21 days | Subjects completed the FLU-PRO questionnaire including global assessment questions daily in the evening. The time from first dose to ability to return to usual health is the time in hours from the first dose of study medication to the first time when the subject answered Have you returned to your usual health? with yes for two consecutive daily diary periods without the use of symptom relief medication. |
| Response Misclassification Rate Compared to Usual Health | 21 days | The proportion of patient diaries misclassified by the response definition used for the primary efficacy analysis compared to patient reported usual health. A diary was considered misclassified if the response definition predicted responded and the patient reported not being at usual health or if the response definition predicted not responded and the patient reported being at usual health. |
| Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Days 2, 3, and 7 | Proportion of subjects with nasopharyngeal swab collected testing positive for Enterovirus/Rhinovirus (EV/RV) infection by RT-PCR at each time point. |
| Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Days 2, 3, and 7 | Changes from baseline to day 2, baseline to day 3, and baseline to day 7 in EV/RV virus titer measured by quantitative RT-PCR. Samples negative for EV/RV were assigned the value of the limit of detection for the RT-PCR assay. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nitazoxanide Two Nitazoxanide 300 mg tablets orally twice daily for 5 days | 872 |
| Placebo Two placebo tablets orally twice daily for 5 days | 884 |
| Total | 1,756 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Other reasons included failure to attend follow up visits or inability to use the eDiary. | 11 | 15 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Withdrawal by Subject | 12 | 9 |
Baseline characteristics
| Characteristic | Nitazoxanide | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 14.82 | 37.2 years STANDARD_DEVIATION 14.6 | 37.3 years STANDARD_DEVIATION 14.38 |
| Baseline Illness Severity, ITTI Population Mild | 40 Participants | 74 Participants | 34 Participants |
| Baseline Illness Severity, ITTI Population Moderate | 147 Participants | 296 Participants | 149 Participants |
| Baseline Illness Severity, ITTI Population No cold symptoms | 3 Participants | 5 Participants | 2 Participants |
| Baseline Illness Severity, ITTI Population Severe | 83 Participants | 176 Participants | 93 Participants |
| Baseline Illness Severity, ITTI Population Very severe | 13 Participants | 33 Participants | 20 Participants |
| Baseline Patient-Reported Health Status, ITTI Population At Usual Health | 35 Participants | 77 Participants | 42 Participants |
| Baseline Patient-Reported Health Status, ITTI Population Not At Usual Health | 251 Participants | 507 Participants | 256 Participants |
| Baseline Symptom Interference in Activities, ITTI Population A little bit | 74 Participants | 160 Participants | 86 Participants |
| Baseline Symptom Interference in Activities, ITTI Population Not at all | 48 Participants | 85 Participants | 37 Participants |
| Baseline Symptom Interference in Activities, ITTI Population Quite a bit | 58 Participants | 117 Participants | 59 Participants |
| Baseline Symptom Interference in Activities, ITTI Population Somewhat | 87 Participants | 181 Participants | 94 Participants |
| Baseline Symptom Interference in Activities, ITTI Population Very much | 19 Participants | 41 Participants | 22 Participants |
| Baseline Symptom Score, ITTI Population | 1.4 mean of patient-reported symptom ratings STANDARD_DEVIATION 0.59 | 1.4 mean of patient-reported symptom ratings STANDARD_DEVIATION 0.59 | 1.4 mean of patient-reported symptom ratings STANDARD_DEVIATION 0.59 |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population About the same as yesterday | 89 Participants | 169 Participants | 80 Participants |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population A little better than yesterday | 24 Participants | 44 Participants | 20 Participants |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population A little worse than yesterday | 79 Participants | 172 Participants | 93 Participants |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population Much better than yesterday | 5 Participants | 9 Participants | 4 Participants |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population Much worse than yesterday | 31 Participants | 74 Participants | 43 Participants |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population Somewhat better than yesterday | 11 Participants | 21 Participants | 10 Participants |
| Baseline Symptom Severity Compared to Yesterday, ITTI Population Somewhat worse than yesterday | 47 Participants | 95 Participants | 48 Participants |
| BMI | 30.3 kg/m^2 STANDARD_DEVIATION 8.05 | 30.3 kg/m^2 STANDARD_DEVIATION 8.07 | 30.3 kg/m^2 STANDARD_DEVIATION 8.09 |
| Height | 167.0 cm STANDARD_DEVIATION 9.83 | 168.0 cm STANDARD_DEVIATION 10.11 | 168.3 cm STANDARD_DEVIATION 10.38 |
| Race/Ethnicity, Customized Black or African American | 173 Participants | 348 Participants | 175 Participants |
| Race/Ethnicity, Customized Hispanic | 124 Participants | 274 Participants | 150 Participants |
| Race/Ethnicity, Customized Other | 24 Participants | 47 Participants | 23 Participants |
| Race/Ethnicity, Customized White | 551 Participants | 1087 Participants | 536 Participants |
| Respiratory Infection(s) Adenovirus | 2 Participants | 10 Participants | 8 Participants |
| Respiratory Infection(s) Coronavirus (NL63, HKU1, 229E, or OC43) | 63 Participants | 117 Participants | 54 Participants |
| Respiratory Infection(s) Enterovirus/Rhinovirus | 286 Participants | 584 Participants | 298 Participants |
| Respiratory Infection(s) Human Metapneumovirus | 5 Participants | 11 Participants | 6 Participants |
| Respiratory Infection(s) Influenza A | 6 Participants | 9 Participants | 3 Participants |
| Respiratory Infection(s) Mycoplasma pneumoniae | 0 Participants | 1 Participants | 1 Participants |
| Respiratory Infection(s) Parainfluenza | 38 Participants | 74 Participants | 36 Participants |
| Respiratory Infection(s) Respiratory Syncytial Virus (RSV) | 19 Participants | 37 Participants | 18 Participants |
| Sex: Female, Male Female | 613 Participants | 1180 Participants | 567 Participants |
| Sex: Female, Male Male | 259 Participants | 576 Participants | 317 Participants |
| Smoking Status Current Smoker | 166 Participants | 315 Participants | 149 Participants |
| Smoking Status Never Smoked | 586 Participants | 1198 Participants | 612 Participants |
| Smoking Status Past Smoker | 120 Participants | 243 Participants | 123 Participants |
| Time from Onset of Symptoms at First Study Drug Intake (hours) | 26.6 hours STANDARD_DEVIATION 9.1 | 26.5 hours STANDARD_DEVIATION 9.1 | 26.3 hours STANDARD_DEVIATION 9.1 |
| Weight | 85.6 kg STANDARD_DEVIATION 25.03 | 85.7 kg STANDARD_DEVIATION 23.9 | 85.8 kg STANDARD_DEVIATION 22.74 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 872 | 0 / 884 |
| other Total, other adverse events | 200 / 872 | 58 / 884 |
| serious Total, serious adverse events | 4 / 872 | 1 / 884 |
Outcome results
Primary
Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint)
Subjects used the FLU-PRO questionnaire once daily in the evening to score the severity of 32 FLU-PRO symptoms. Symptom response was deemed achieved when the rating for each of the 32 FLU-PRO symptoms was ≤ its assigned threshold for 2 consecutive daily diary periods without use of symptom relief medication. The symptom response thresholds were developed by applying an algorithm to blinded symptoms data to select the set of 32 symptom thresholds most closely associated with patient-reported usual health.
Time frame: Up to 21 days
Population: The primary efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide | Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint) | 122.5 hours |
| Placebo | Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint) | 137.1 hours |
p-value: 0.4009Gehan-Wilcoxon
Secondary
Proportions Experiencing Complications of EV/RV Infection
Complications of colds due to EV/RV infection include pneumonia, otitis media, bronchitis, sinusitis, exacerbations of asthma or COPD, worsening of pre-existing health conditions, secondary infections requiring systemic antibiotic use, hospitalization due to cold or complications of the cold, and death due to cold or complications of the cold. Proportions experiencing complications of EV/RV infection were compared across treatment groups.
Time frame: 28 days
Population: The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nitazoxanide | Proportions Experiencing Complications of EV/RV Infection | 12 Participants |
| Placebo | Proportions Experiencing Complications of EV/RV Infection | 20 Participants |
p-value: 0.2057Fisher Exact
Secondary
Time From First Dose to Ability to Perform All Normal Activities
Subjects completed a diary including rating ability to perform normal activities on a scale from 0 (able to perform no normal activities) to 10 (able to perform all normal activities) daily in the evening. The time from first dose to ability to perform all normal activities is the time in hours between the first dose of study medication and that time when the subject first reported a score of 10 (able to perform all normal activities) for two consecutive daily diary periods without use of symptom relief medication.
Time frame: Up to 21 days
Population: The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide | Time From First Dose to Ability to Perform All Normal Activities | 174.3 hours |
| Placebo | Time From First Dose to Ability to Perform All Normal Activities | 175.4 hours |
p-value: 0.1923Gehan-Wilcoxon
Other Pre-specified
Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer
Changes from baseline to day 2, baseline to day 3, and baseline to day 7 in EV/RV virus titer measured by quantitative RT-PCR. Samples negative for EV/RV were assigned the value of the limit of detection for the RT-PCR assay.
Time frame: Days 2, 3, and 7
Population: Analysis population includes subjects with laboratory-confirmed EV/RV who were positive for EV/RV at the preceding swab collection time point. Per protocol, day 2 and 3 visits were optional.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nitazoxanide | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Day 2 | -0.2203 log10 RNA copies/mL | Standard Error 0.0934 |
| Nitazoxanide | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Day 3 | -0.5577 log10 RNA copies/mL | Standard Error 0.1272 |
| Nitazoxanide | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Day 7 | -1.5113 log10 RNA copies/mL | Standard Error 0.1373 |
| Placebo | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Day 2 | -0.4186 log10 RNA copies/mL | Standard Error 0.0884 |
| Placebo | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Day 3 | -0.8282 log10 RNA copies/mL | Standard Error 0.1053 |
| Placebo | Analysis of Change From Baseline to Days 2, 3 and 7 in EV/RV Virus Titer | Day 7 | -1.6470 log10 RNA copies/mL | Standard Error 0.1231 |
Comparison: Comparison for day 2p-value: 0.1239t-test, 2 sided
Comparison: Comparison for day 3p-value: 0.1022t-test, 2 sided
Comparison: Comparison for day 7p-value: 0.46213t-test, 2 sided
Post Hoc
Correlation Coefficient for Sustained Response and Return to Usual Health
The correlation coefficient between sustained response and return to usual health was calculated for the pooled ITTI population (i.e., not by treatment group) as a measure of association between the primary endpoint response definition and its intended anchor, patient-reported return to usual health.
Time frame: 21 days
Population: The intent-to-treat-infected (ITTI) population consisted of all subjects positive for EV/RV at Baseline. Consistent with calculation of the response definition misclassification rate, the correlation coefficient was calculated for all subjects in the ITTI population regardless of treatment group assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | Correlation Coefficient for Sustained Response and Return to Usual Health | 0.43 correlation coefficient |
Other Pre-specified
Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7
Proportion of subjects with nasopharyngeal swab collected testing positive for Enterovirus/Rhinovirus (EV/RV) infection by RT-PCR at each time point.
Time frame: Days 2, 3, and 7
Population: The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nitazoxanide | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Day 2 | 0.81 proportion of participants |
| Nitazoxanide | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Day 3 | 0.79 proportion of participants |
| Nitazoxanide | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Day 7 | 0.66 proportion of participants |
| Placebo | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Day 2 | 0.81 proportion of participants |
| Placebo | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Day 3 | 0.79 proportion of participants |
| Placebo | Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7 | Day 7 | 0.76 proportion of participants |
Comparison: Comparison for study day 2p-value: 1Fisher Exact
Comparison: Comparison for study day 3p-value: 0.9142Fisher Exact
Comparison: Comparison for study day 7p-value: 0.0132Fisher Exact
Other Pre-specified
Response Misclassification Rate Compared to Usual Health
The proportion of patient diaries misclassified by the response definition used for the primary efficacy analysis compared to patient reported usual health. A diary was considered misclassified if the response definition predicted responded and the patient reported not being at usual health or if the response definition predicted not responded and the patient reported being at usual health.
Time frame: 21 days
Population: The intent-to-treat-infected (ITTI) population consisted of all subjects positive for EV/RV at Baseline. Per the Statistical Analysis Plan, the response definition misclassification rate was to be calculated prior to unblinding including all data for subjects in the ITTI population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitazoxanide | Response Misclassification Rate Compared to Usual Health | 0.21915 n diaries misclassified/n diaries |
Other Pre-specified
Time to Return to Usual Health
Subjects completed the FLU-PRO questionnaire including global assessment questions daily in the evening. The time from first dose to ability to return to usual health is the time in hours from the first dose of study medication to the first time when the subject answered Have you returned to your usual health? with yes for two consecutive daily diary periods without the use of symptom relief medication.
Time frame: 21 days
Population: The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide | Time to Return to Usual Health | 154.1 hours |
| Placebo | Time to Return to Usual Health | 174.9 hours |
p-value: 0.0712Gehan-Wilcoxon
Post Hoc
Time to Return to Usual Health, Modified ITTI Population
Examination of Baseline disease characteristics revealed many subjects reporting via the Baseline FLU-PRO questionnaire that they are at their usual state of health, that symptoms do not interfere with any usual activities, and/or that symptoms are already improving. The pre-specified analysis of Time to Return for Usual Health was repeated for the population with Baseline subject-reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day. Time to Return to Usual Health is the time in hours between the first dose of study medication and the first time at which the subject answered Have you returned to your Usual Health today? via the daily FLU-PRO questionnaire with a yes for two consecutive diary periods without use of symptom relief medication.
Time frame: 21 days
Population: Modified ITTI population consists of 387 subjects with laboratory-confirmed EV/RV infection and Baseline subject-reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day. Assessment was completed via the Baseline FLU-PRO questionnaire.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide | Time to Return to Usual Health, Modified ITTI Population | 153.7 hours |
| Placebo | Time to Return to Usual Health, Modified ITTI Population | 195.0 hours |
p-value: 0.014Gehan-Wilcoxon
Post Hoc
Time to Sustained Clinical Recovery
Alternative means of endpoint construction were pursued to strengthen the relationship between symptoms-based endpoint measures and subject global assessments of health. Time to Sustained Clinical Recovery is an endpoint based on evidence of meaningful within-subject change sustained for the duration of the study. Time to Sustained Clinical Recovery is the time in hours from the first dose of study medication to the first time at which the subject reports a decrease in total FLU-PRO score from the previous diary with assessment that symptoms are at least somewhat better than yesterday, no oral temperature ≥100.4 F in the prior 24 hours, and no future increase in any of the FLU-PRO domains except within validated background levels.
Time frame: 21 days
Population: The efficacy (intent-to-treat infected, ITTI) population consisted of 584 subjects (N=286 in NTZ group, N=298 in Placebo group) with laboratory-confirmed Enterovirus/Rhinovirus (EV/RV) infection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide | Time to Sustained Clinical Recovery | 171.4 hours |
| Placebo | Time to Sustained Clinical Recovery | 221.5 hours |
p-value: 0.0112Gehan-Wilcoxon
Post Hoc
Time to Sustained Clinical Recovery, Modified ITTI Population
Analysis of Time to Sustained Clinical Recovery was repeated for the population with Baseline subject-reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day. Time to Sustained Clinical Recovery is the time in hours from the first dose of study medication to the first time at which the subject reports a decrease in total FLU-PRO score from the previous diary with assessment that symptoms are at least somewhat better than yesterday, no oral temperature ≥100.4 F in the prior 24 hours, and no future increase in any of the FLU-PRO domains except within validated background levels.
Time frame: 21 days
Population: Modified ITTI population consists of 387 subjects with laboratory-confirmed EV/RV infection and Baseline subject-reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day. Assessment was completed via the Baseline FLU-PRO questionnaire.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nitazoxanide | Time to Sustained Clinical Recovery, Modified ITTI Population | 150.3 hours |
| Placebo | Time to Sustained Clinical Recovery, Modified ITTI Population | 244.1 hours |
p-value: <0.0001Gehan-Wilcoxon