acute uncomplicated influenza MedDRA version: 16.1 Level: PT Classification code 10022000 Term: Influenza System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Nitazoxanide
Product Code: NTZ
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NITAZOXANIDE
CAS Number: 55981-09-4
Other descriptive name: PH-5776, NTZ or Alinia®
Concentrat
Sponsors
Romark Laboratories L.C.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 13 to 65 years 2. Presence of clinical signs and/or symptoms consistent with an acute illness compatible with influenza infection (each of the following is required): a) oral temperature of =100.4 °F or =38 °C (obtained in office or self-measured within 12 hours prior to screening – if self-measured, subject must also have taken an antipyretic within 4 hours prior to screening) AND b) at least one of the following respiratory symptoms (cough, sore throat, nasal obstruction,) that is considered by the patient to be moderate or severe (greater than mild severity), AND c) one of the following constitutional symptoms (fatigue, headache, myalgia, feverishness) that is considered by the patient to be moderate or severe (greater than mild severity). 3. Confirmation of influenza A or B infection in the local community by one of the following means: a) the institution's local laboratory, or b) the local public health system or c) the national public health system or d) a laboratory of a recognized national or multinational influenza surveillance scheme. 4. Onset of illness no more than 48 hours before enrollment in the trial. Note: 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 subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom. 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 patient diary. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Severity of illness requiring or anticipated to require in-hospital care or subject defined as being at high risk of complications from influenza infection according to the IDSA guidelines for seasonal influenza in adults and children (CID 2009:48) or current CDC criteria. Current criteria for persons 12-65 years of age who are at risk of influenza complications include (list to be reviewed and updated as required prior to initiation of the study and at least monthly during the study): ? Persons with asthma or other chronic pulmonary diseases, such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults. ? Persons with hemodynamically significant cardiac disease. ? Persons who have immunosuppressive disorders or who are receiving immunosuppressive therapy. ? HIV-infected persons. ? Persons with sickle cell anemia or other hemoglobinopathies. ? Persons with diseases requiring long-term aspirin therapy, such as rheumatoid arthritis or Kawasaki disease. Persons with chronic renal dysfunction. ? Persons with liver disorders. ? Persons with cancer. ? Persons with chronic metabolic disease, such as diabetes mellitus, inherited metabolic disorders and mitochondrial disorders. ? Persons with neuromuscular disorders, seizure disorders or cognitive dysfunction that may compromise the handling of respiratory secretions. ? Residents of any age of nursing homes or other long-term care institutions. ? Persons who are morbidly obese (Body Mass Index =40) ? American Indians (seemed to be at higher risk of complications last flu season) ? Alaskan natives (seemed to be at higher risk of complications last flu season) 2. Females of childbearing potential who are either pregnant, breast-feeding or are sexually active without the use of birth control. Female patients 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 ovariectomy. 3. Vaccination for seasonal influenza on or after (i) August 1, 2012 in the case of subjects enrolled during the 2012/2013 flu season in the United States, (ii) February 1, 2013 in the case of subjects enrolled during the 2013 flu season in Australia or New Zealand, (iii) August 1, 2013 in the case of subjects enrolled during the 2013/2014 flu season in the United States, Canada, Europe, or other countries in the Northern Hemisphere, or February 1, 2014 in the case of subjects enrolled during the 2014 flu season in Australia or New Zealand. 4. Receipt of any dose of NTZ, OST, zanamivir, amantadine or rimantadine within 30 days prior to screening. 5. Prior treatment with any investigational drug therapy within 30 days prior to screening. 6. Subjects with active respiratory allergies or subjects expected to require anti-allergy medi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Evaluate the effect of NTZ administered 600 mg orally b.i.d. for 5 days on time to alleviation of symptoms of acute uncomplicated influenza compared to that of a placebo. - Evaluate the effect of combination therapy with NTZ 600 mg plus OST 75 mg administered orally b.i.d. for 5 days on time to alleviation of symptoms of acute uncomplicated influenza compared to that of monotherapy with NTZ 600 mg b.i.d. for 5 days and monotherapy with OST 75 mg b.i.d. for 5 days;Secondary Objective: a) Change in influenza virus titer (by TCID50) and viral RNA titer (by RT-PCR) over time ; b) Time to cessation of shedding of infectious virus (by TCID50) and of viral RNA (by RT-PCR); c) Time to return to normal activity; d) Time to alleviation of each individual symptom; e) Severity of disease expressed as “score-hours” (symptom score multiplied by duration of symptom) using data collected from patient diaries; f) Complications of influenza including physician-diagnosed secondary illnesses, antibiotic use and hospitalizations; g) Time lost from work; and h) Selection of drug-resistant influenza virus.;Primary end point(s): Time to alleviation of all clinical symptoms of influenza as reported by the subjects.;Timepoint(s) of evaluation of this end point: Blood samples will be collected for all subjects at baseline, day 7 and day 28. Urine samples will be collected at baseline and day 7. Nasopharyngeal swabs will be collected at baseline, days 7, 14 and 28 for all subjects and on days 2, 3, 4 and 5 for a subset of subjects (=20%). A blood sample will be collected on days 3 and 5 for the same subset of subjects for pharmacokinetics. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): i. Change in influenza virus titer (TCID50) ii. Time to cessation of viral shedding iii. Time to return to normal activity iv. Time to alleviation of each individual symptom v. Severity of disease expressed in “score-hours” (symptom scores multiplied by duration of symptoms) vi. Complications of influenza including physician-diagnosed secondary illnesses, antibiotic use and hospitalizations vii. Time lost from work viii. Selection of oseltamivir or tizoxanide-resistant influenza virus | — |
Countries
Australia, Belgium, Canada, New Zealand, United States
Contacts
Public ContactYelen Concepcion
Romark Laboratories L.C.
Outcome results
None listed