Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection

Study Overview
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Brief Summary
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Trial to evaluate efficacy and safety of nitazoxanide in the treatment of colds due to Enterovirus/Rhinovirus infection

Detailed Description
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Multicenter, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety of nitazoxanide in the treatment of colds due to Enterovirus/Rhinovirus infection

Official Title
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A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Colds Due to Enterovirus/Rhinovirus Infection

Conditions
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Enterovirus, Rhinovirus

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects at least 12 years of age Presence of clinical signs and/or symptoms consistent with an acute illness compatible with EV/RV infection (each of the following is required): 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 Presence of cough, sore throat or nasal obstruction. 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. 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. 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: Persons requiring or anticipated to require in-hospital care Cystic fibrosis Cardiac arrhythmia Immunologic disorders or receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants, immunomodulatory therapies for certain autoimmune diseases) Untreated HIV infection or treated HIV infection with a CD4 count below 350 cells/mm3 in the last 6 months Persons with sickle cell anemia or other hemoglobinopathies Poorly controlled insulin-dependent diabetes mellitus (HbA1C >8.0%) Concurrent infection at the screening examination that requires systemic antimicrobial therapy 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. Females who are breastfeeding Receipt of any dose of NTZ within 30 days prior to screening Prior treatment with any investigational drug therapy within 30 days prior to screening Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets Subjects unable to take oral medications 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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitazoxanide<br>Two Nitazoxanide 300 mg tablets orally twice daily for 5 days | Drug: Nitazoxanide<br>* Nitazoxanide 600 mg administered orally twice daily for five days<br>* Other names: NT-300;|
| Placebo Comparator: Placebo<br>Two placebo tablets orally twice daily for 5 days | Drug: Placebo<br>* Placebo administered orally twice daily for five days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 21 days | 
| 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. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enterovirus, Rhinovirus