Clinical trial NCT03336619: A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Uncomplicated Influenza
Official title: A Phase III, Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide in the Treatment of Uncomplicated Influenza
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Influenza
Lead sponsor: Romark Laboratories L.C.
Sponsor class: INDUSTRY
First posted: 2017-11-08
Enrollment: 1030
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Trial to evaluate efficacy and safety of nitazoxanide (NTZ) in the treatment of uncomplicated influenza.

Detailed description: A multicenter, randomized, double-blind, placebo controlled trial to evaluate efficacy and safety of nitazoxanide (NTZ) in the treatment of uncomplicated influenza.

Eligibility criteria: 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 influenza infection (each of the following is required):

   1. oral temperature ≥99.4°F or ≥37.4°C (obtained in office or self- measured within 12 hours prior to screening - if self-measured, subjects must also have taken an antipyretic within 4 hours prior to screening), AND
   2. at least one of the following respiratory symptoms (cough, sore throat, nasal obstruction), AND
   3. one of the following constitutional symptoms (fatigue, headache, myalgia, feverishness).
3. Confirmation of influenza A or B infection in the local community by one of the following means:

   1. the institution's local laboratory,
   2. the local public health system,
   3. the national public health system, OR
   4. a laboratory of a recognized national or multinational influenza surveillance scheme.
4. Onset of illness no more than 40 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.

Exclusion Criteria:

1. Severity of illness requiring or anticipated to require in-hospital care.
2. Moderate or severe persistent asthma.
3. Cystic fibrosis in children.
4. Stage III or IV (severe or very severe) chronic obstructive pulmonary disease (COPD).
5. Class III or IV congestive heart failure (at least marked limitation of physical activity in which minimal ordinary activity results in fatigue, palpitation, dyspnea, or angina pain)
6. Arrhythmia
7. Immunosuppressive disorders or who are receiving immunosuppressive therapy (e.g., for organ or bone marrow transplants)
8. Untreated HIV infection or treated HIV infection with a CD4 count below 350 cells/mm3 in the last 6 months
9. Persons with sickle cell anemia or other hemoglobinopathies
10. Poorly controlled insulin-dependent diabetes mellitus (HBA1C \> 8%)
11. Residents of any age of nursing homes or other long-term care institutions
12. Concurrent infection at the screening examination that requires systemic antimicrobial therapy.
13. Females of childbearing potential who are either pregnant, breast-feeding or are 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.
14. Receipt of any dose of NTZ, oseltamivir, zanamivir, peramivir, laninamivir, baloxavir, amantadine or rimantadine within 3 days prior to screening.
15. Prior treatment with any investigational drug therapy within 30 days prior to screening.
16. Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies.
17. Known sensitivity to NTZ or any of the excipients comprising the NTZ tablets.
18. Subjects unable to take oral medications.
19. Presence of any pre-existing illness that, in the opinion of the Investigator, would place the subject at an unreasonably increased risk through participation in this study.
20. Subjects who, in the judgment of the Investigator, will be unlikely to comply with the requirements of this protocol.

Primary outcomes:
measure: Time From First Dose to Symptom Response
timeFrame: Up to 21 days
Secondary outcomes:
measure: Time From First Dose to Ability to Perform All Normal Activities
timeFrame: Up to 21 days
measure: Number of Subjects Experiencing One or More Complications of Influenza
timeFrame: Up to 21 days
measure: Time to Symptom Response Excluding the FLU-PRO Gastrointestinal and Eye Domains
timeFrame: Up to 21 days
Other outcomes:
measure: Time to Return to Usual Health
timeFrame: 21 days
measure: Proportion of Diaries Misclassified by Novel Response Definition
timeFrame: 21 days
Locations:
city: Alabaster
country: United States
facility: Vanguard Study Site
state: Alabama
city: Birmingham
country: United States
facility: Vanguard Study Site
state: Alabama
city: Birmingham
country: United States
facility: Vanguard Study Site
state: Alabama
city: Hoover
country: United States
facility: Vanguard Study Site
state: Alabama
city: Pelham
country: United States
facility: Vanguard Study Site
state: Alabama
city: Goodyear
country: United States
facility: Vanguard Study Site
state: Arizona
city: Tolleson
country: United States
facility: Vanguard Study Site
state: Arizona
city: Hot Springs
country: United States
facility: Vanguard Study Site
state: Arkansas
city: Anaheim
country: United States
facility: Vanguard Study Site
state: California
city: Westminster
country: United States
facility: Vanguard Study Site
state: California
city: Lauderdale Lakes
country: United States
facility: Vanguard Study Site
state: Florida
city: Orlando
country: United States
facility: Vanguard Study Site
state: Florida
city: Valparaiso
country: United States
facility: Vanguard Study Site
state: Indiana
city: New Orleans
country: United States
facility: Vanguard Study Site
state: Louisiana
city: Saint Louis
country: United States
facility: Vanguard Study Site
state: Missouri
city: Missoula
country: United States
facility: Vanguard Study Site
state: Montana
city: Brooklyn
country: United States
facility: Vanguard Study Site
state: New York
city: Cincinnati
country: United States
facility: Vanguard Study Site
state: Ohio
city: Columbus
country: United States
facility: Vanguard Study Site
state: Ohio
city: Dayton
country: United States
facility: Vanguard Study Site
state: Ohio
city: Medford
country: United States
facility: Vanguard Study Site
state: Oregon
city: Rapid City
country: United States
facility: Vanguard Study Site
state: South Dakota
city: Jackson
country: United States
facility: Vanguard Study Site
state: Tennessee
city: Smyrna
country: United States
facility: Vanguard Study Site
state: Tennessee
city: Austin
country: United States
facility: Vanguard Study Site
state: Texas
city: Carrollton
country: United States
facility: Vanguard Study Site
state: Texas
city: Dallas
country: United States
facility: Vanguard Study Site
state: Texas
city: Dallas
country: United States
facility: Vanguard Study Site
state: Texas
city: Fort Worth
country: United States
facility: Vanguard Study Site
state: Texas
city: Houston
country: United States
facility: Vanguard Study Site
state: Texas
city: Pharr
country: United States
facility: Vanguard Study Site
state: Texas
city: Plano
country: United States
facility: Vanguard Study Site
state: Texas
city: Plano
country: United States
facility: Vanguard Study Site
state: Texas
city: Saint George
country: United States
facility: Vanguard Study Site
state: Utah
city: Morayfield
country: Australia
facility: Vanguard Study Site
state: Queensland
city: Sherwood
country: Australia
facility: Vanguard Study Site
state: Queensland
city: Victoria Point
country: Australia
facility: Vanguard Study Site
state: Queensland
city: Ponce
country: Puerto Rico
facility: Vanguard Study Site
Study officials:
affiliation: Romark Laboratories L.C.
name: Jean-Francois Rossignol, M.D., Ph.D.
role: STUDY_DIRECTOR
References: