Trial Outcomes & Findings for Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection (NCT NCT03605862)
NCT ID: NCT03605862
Last Updated: 2022-04-14
Results Overview
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.
COMPLETED
PHASE3
1756 participants
Up to 21 days
2022-04-14
Participant Flow
Participant milestones
| Measure |
Nitazoxanide
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Overall Study
STARTED
|
872
|
884
|
|
Overall Study
COMPLETED
|
844
|
858
|
|
Overall Study
NOT COMPLETED
|
28
|
26
|
Reasons for withdrawal
| Measure |
Nitazoxanide
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
12
|
9
|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Physician Decision
|
3
|
1
|
|
Overall Study
"Other" reasons included failure to attend follow up visits or inability to use the eDiary.
|
11
|
15
|
Baseline Characteristics
Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
Baseline characteristics by cohort
| Measure |
Nitazoxanide
n=872 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=884 Participants
Two placebo tablets orally twice daily for 5 days
|
Total
n=1756 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.1 years
STANDARD_DEVIATION 14.82 • n=872 Participants
|
37.3 years
STANDARD_DEVIATION 14.38 • n=884 Participants
|
37.2 years
STANDARD_DEVIATION 14.60 • n=1756 Participants
|
|
Sex: Female, Male
Female
|
613 Participants
n=872 Participants
|
567 Participants
n=884 Participants
|
1180 Participants
n=1756 Participants
|
|
Sex: Female, Male
Male
|
259 Participants
n=872 Participants
|
317 Participants
n=884 Participants
|
576 Participants
n=1756 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
173 Participants
n=872 Participants
|
175 Participants
n=884 Participants
|
348 Participants
n=1756 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
124 Participants
n=872 Participants
|
150 Participants
n=884 Participants
|
274 Participants
n=1756 Participants
|
|
Race/Ethnicity, Customized
White
|
551 Participants
n=872 Participants
|
536 Participants
n=884 Participants
|
1087 Participants
n=1756 Participants
|
|
Race/Ethnicity, Customized
Other
|
24 Participants
n=872 Participants
|
23 Participants
n=884 Participants
|
47 Participants
n=1756 Participants
|
|
Height
|
167.0 cm
STANDARD_DEVIATION 9.83 • n=872 Participants
|
168.3 cm
STANDARD_DEVIATION 10.38 • n=884 Participants
|
168.0 cm
STANDARD_DEVIATION 10.11 • n=1756 Participants
|
|
Weight
|
85.6 kg
STANDARD_DEVIATION 25.03 • n=872 Participants
|
85.8 kg
STANDARD_DEVIATION 22.74 • n=884 Participants
|
85.7 kg
STANDARD_DEVIATION 23.90 • n=1756 Participants
|
|
BMI
|
30.3 kg/m^2
STANDARD_DEVIATION 8.05 • n=872 Participants
|
30.3 kg/m^2
STANDARD_DEVIATION 8.09 • n=884 Participants
|
30.3 kg/m^2
STANDARD_DEVIATION 8.07 • n=1756 Participants
|
|
Smoking Status
Current Smoker
|
166 Participants
n=872 Participants
|
149 Participants
n=884 Participants
|
315 Participants
n=1756 Participants
|
|
Smoking Status
Past Smoker
|
120 Participants
n=872 Participants
|
123 Participants
n=884 Participants
|
243 Participants
n=1756 Participants
|
|
Smoking Status
Never Smoked
|
586 Participants
n=872 Participants
|
612 Participants
n=884 Participants
|
1198 Participants
n=1756 Participants
|
|
Time from Onset of Symptoms at First Study Drug Intake (hours)
|
26.6 hours
STANDARD_DEVIATION 9.1 • n=872 Participants
|
26.3 hours
STANDARD_DEVIATION 9.1 • n=884 Participants
|
26.5 hours
STANDARD_DEVIATION 9.1 • n=1756 Participants
|
|
Respiratory Infection(s)
Adenovirus
|
2 Participants
n=872 Participants
|
8 Participants
n=884 Participants
|
10 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Coronavirus (NL63, HKU1, 229E, or OC43)
|
63 Participants
n=872 Participants
|
54 Participants
n=884 Participants
|
117 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Enterovirus/Rhinovirus
|
286 Participants
n=872 Participants
|
298 Participants
n=884 Participants
|
584 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Human Metapneumovirus
|
5 Participants
n=872 Participants
|
6 Participants
n=884 Participants
|
11 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Influenza A
|
6 Participants
n=872 Participants
|
3 Participants
n=884 Participants
|
9 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Mycoplasma pneumoniae
|
0 Participants
n=872 Participants
|
1 Participants
n=884 Participants
|
1 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Parainfluenza
|
38 Participants
n=872 Participants
|
36 Participants
n=884 Participants
|
74 Participants
n=1756 Participants
|
|
Respiratory Infection(s)
Respiratory Syncytial Virus (RSV)
|
19 Participants
n=872 Participants
|
18 Participants
n=884 Participants
|
37 Participants
n=1756 Participants
|
|
Baseline Symptom Score, ITTI Population
|
1.4 mean of patient-reported symptom ratings
STANDARD_DEVIATION 0.59 • n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
1.4 mean of patient-reported symptom ratings
STANDARD_DEVIATION 0.59 • n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
1.4 mean of patient-reported symptom ratings
STANDARD_DEVIATION 0.59 • n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Patient-Reported Health Status, ITTI Population
At Usual Health
|
35 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
42 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
77 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Patient-Reported Health Status, ITTI Population
Not At Usual Health
|
251 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
256 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
507 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Illness Severity, ITTI Population
No cold symptoms
|
3 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
2 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
5 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Illness Severity, ITTI Population
Mild
|
40 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
34 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
74 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Illness Severity, ITTI Population
Moderate
|
147 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
149 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
296 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Illness Severity, ITTI Population
Severe
|
83 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
93 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
176 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Illness Severity, ITTI Population
Very severe
|
13 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
20 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
33 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Interference in Activities, ITTI Population
Not at all
|
48 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
37 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
85 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Interference in Activities, ITTI Population
A little bit
|
74 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
86 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
160 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Interference in Activities, ITTI Population
Somewhat
|
87 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
94 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
181 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Interference in Activities, ITTI Population
Quite a bit
|
58 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
59 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
117 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Interference in Activities, ITTI Population
Very much
|
19 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
22 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
41 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
Much better than yesterday
|
5 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
4 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
9 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
Somewhat better than yesterday
|
11 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
10 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
21 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
A little better than yesterday
|
24 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
20 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
44 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
About the same as yesterday
|
89 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
80 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
169 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
A little worse than yesterday
|
79 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
93 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
172 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
Somewhat worse than yesterday
|
47 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
48 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
95 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
|
Baseline Symptom Severity Compared to Yesterday, ITTI Population
Much worse than yesterday
|
31 Participants
n=286 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
43 Participants
n=298 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
74 Participants
n=584 Participants • Analysis population is the primary efficacy (intent-to-treat-infected, ITTI) population with laboratory-confirmed EV/RV infection.
|
PRIMARY outcome
Timeframe: Up to 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time From First Dose to Symptom Response Over 21 Days of Follow up Based Upon the FLU-PRO Instrument (Novel Endpoint)
|
122.5 hours
Interval 58.0 to 244.0
|
137.1 hours
Interval 75.0 to 243.0
|
SECONDARY outcome
Timeframe: Up to 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time From First Dose to Ability to Perform All Normal Activities
|
174.3 hours
Interval 80.0 to 340.0
|
175.4 hours
Interval 105.0 to 318.0
|
SECONDARY outcome
Timeframe: 28 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Proportions Experiencing Complications of EV/RV Infection
|
12 Participants
|
20 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Return to Usual Health
|
154.1 hours
Interval 80.0 to 320.0
|
174.9 hours
Interval 104.0 to 345.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 2, 3, and 7Population: 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.
Proportion of subjects with nasopharyngeal swab collected testing positive for Enterovirus/Rhinovirus (EV/RV) infection by RT-PCR at each time point.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7
Day 2
|
0.81 proportion of participants
|
0.81 proportion of participants
|
|
Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7
Day 3
|
0.79 proportion of participants
|
0.79 proportion of participants
|
|
Proportion Positive for EV/RV by RT-PCR at Days 2, 3 and 7
Day 7
|
0.66 proportion of participants
|
0.76 proportion of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 2, 3, and 7Population: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
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
|
-0.4186 log10 RNA copies/mL
Standard Error 0.0884
|
|
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
|
-0.8282 log10 RNA copies/mL
Standard Error 0.1053
|
|
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
|
-1.6470 log10 RNA copies/mL
Standard Error 0.1231
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=584 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Response Misclassification Rate Compared to Usual Health
|
0.21915 n diaries misclassified/n diaries
|
—
|
POST_HOC outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=584 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Correlation Coefficient for Sustained Response and Return to Usual Health
|
0.43 correlation coefficient
|
—
|
POST_HOC outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=183 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=204 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Return to Usual Health, Modified ITTI Population
|
153.7 hours
Interval 96.0 to 317.0
|
195.0 hours
Interval 123.0 to 365.0
|
POST_HOC outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=286 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=298 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Sustained Clinical Recovery
|
171.4 hours
Interval 81.0 to 411.0
|
221.5 hours
Interval 103.0 to 504.0
|
POST_HOC outcome
Timeframe: 21 daysPopulation: 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.
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.
Outcome measures
| Measure |
Nitazoxanide
n=183 Participants
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=204 Participants
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Time to Sustained Clinical Recovery, Modified ITTI Population
|
150.3 hours
Interval 81.0 to 322.0
|
244.1 hours
Interval 119.0 to 504.0
|
Adverse Events
Nitazoxanide
Placebo
Serious adverse events
| Measure |
Nitazoxanide
n=872 participants at risk
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=884 participants at risk
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Cardiac disorders
Cardiac failure congestive
|
0.11%
1/872 • Number of events 1 • 28 days or until resolution of all adverse events, whichever occurred later.
|
0.00%
0/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.11%
1/872 • Number of events 1 • 28 days or until resolution of all adverse events, whichever occurred later.
|
0.00%
0/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Infections and infestations
Gastroenteritis viral
|
0.11%
1/872 • Number of events 1 • 28 days or until resolution of all adverse events, whichever occurred later.
|
0.00%
0/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Infections and infestations
Post procedural infection
|
0.11%
1/872 • Number of events 1 • 28 days or until resolution of all adverse events, whichever occurred later.
|
0.00%
0/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Infections and infestations
Urosepsis
|
0.11%
1/872 • Number of events 1 • 28 days or until resolution of all adverse events, whichever occurred later.
|
0.00%
0/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/872 • 28 days or until resolution of all adverse events, whichever occurred later.
|
0.11%
1/884 • Number of events 1 • 28 days or until resolution of all adverse events, whichever occurred later.
|
Other adverse events
| Measure |
Nitazoxanide
n=872 participants at risk
Two Nitazoxanide 300 mg tablets orally twice daily for 5 days
|
Placebo
n=884 participants at risk
Two placebo tablets orally twice daily for 5 days
|
|---|---|---|
|
Renal and urinary disorders
Chromaturia
|
17.5%
153/872 • 28 days or until resolution of all adverse events, whichever occurred later.
|
1.1%
10/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
53/872 • 28 days or until resolution of all adverse events, whichever occurred later.
|
4.3%
38/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
|
Gastrointestinal disorders
Nausea
|
2.8%
24/872 • 28 days or until resolution of all adverse events, whichever occurred later.
|
2.1%
19/884 • 28 days or until resolution of all adverse events, whichever occurred later.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place