Clinical trial NCT01610245: Safety and Efficacy Study of Nitazoxanide in the Treatment of Acute Uncomplicated Influenza
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide and Nitazoxanide Plus Oseltamivir in the Treatment of Acute 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: 2012-06-01
Enrollment: 1941
Sex: ALL
Minimum age (years): 13
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a global multicenter randomized factorial double-blind, placebo-controlled trial designed to evaluate (i) efficacy and safety of nitazoxanide 600 mg administered orally twice daily for five days compared to a placebo in the treatment of acute uncomplicated influenza and (ii) efficacy and safety of combination therapy with nitazoxanide 600 mg plus Oseltamivir 75 mg co-administered orally twice daily for five days compared to nitazoxanide monotherapy (600 mg b.i.d. for 5 days) and Oseltamivir monotherapy (75 mg b.i.d. for 5 days) in the treatment of acute uncomplicated influenza.


Eligibility criteria: Inclusion Criteria:

1. Age 13 to 65 years
2. Presence of clinical signs and/or symptoms consistent with acute illness compatible with influenza infection (each of the following is required):

   1. 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
   2. 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
   3. 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:

   1. the institution's local laboratory, or
   2. the local public health system, or
   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 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.

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 Infectious Diseases Society of America (IDSA) guidelines for seasonal influenza in adults and children (Committee of Infectious Diseases (CID) 2009:48) or current Centers for Disease Control and Prevention (CDC) criteria. Current criteria for persons 13-65 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):

   1. Persons with asthma or other chronic pulmonary diseases, such as cystic fibrosis in children or chronic obstructive pulmonary disease in adults.
   2. Persons with hemodynamically significant cardiac disease.
   3. Persons who have immunosuppressive disorders or who are receiving immunosuppressive therapy.
   4. HIV-infected persons.
   5. Persons with sickle cell anemia or other hemoglobinopathies.
   6. Persons with diseases requiring long-term aspirin therapy, such as rheumatoid arthritis or Kawasaki disease.
   7. Persons with chronic renal dysfunction.
   8. Persons with liver disorders.
   9. Persons with cancer.
   10. Persons with chronic metabolic disease, such as diabetes mellitus, inherited metabolic disorders and mitochondrial disorders.
   11. Persons with neuromuscular disorders, seizure disorders or cognitive dysfunction that may compromise the handling of respiratory secretions.
   12. Residents of any age of nursing homes or other long-term care institutions.
   13. Persons who are morbidly obese (Body Mass Index ≥40)
   14. American Indians (seemed to be at higher risk of complications last flu season)
   15. 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 intrauterine device (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, or 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 iv. February 1, 2014 in the case of subjects enrolled during the 2014 flu season in Australia or New Zealand, or v. August 1, 2014 in the case of subjects enrolled during the 2014/2015 flu season in the United States, Canada, Europe, or other countries in the Northern Hemisphere.
4. Receipt of any dose of nitazoxanide, oseltamivir, 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 medications during the study period for respiratory allergies.
7. Known sensitivity to Nitazoxanide or any of the excipients comprising the Nitazoxanide tablets.
8. Known sensitivity to Oseltamivir or any of the excipients comprising the Oseltamivir capsules.
9. Subjects unable to take oral medications.
10. Subject has chronic kidney or liver disease (including Hepatitis A,B or C) or known impaired hepatic and/or renal function.
11. Presence of any other pre-existing chronic infection that is undergoing or requiring medical therapy.
12. 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.
13. Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.

Primary outcomes:
measure: Time to resolution of all clinical symptoms of influenza as reported by the subjects
timeFrame: Up to 28 days
Secondary outcomes:
measure: Time to resolution of each individual symptom of influenza
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Influence Study Site
state: Alabama
city: Dothan
country: United States
facility: Influence Study Site
state: Alabama
city: Hoover
country: United States
facility: Influence Study Site
state: Alabama
city: Mobile
country: United States
facility: Influence Study Site
state: Alabama
city: Mesa
country: United States
facility: Influence Study Site
state: Arizona
city: Mesa
country: United States
facility: Influence Study Site
state: Arizona
city: Tucson
country: United States
facility: Influence Study Site
state: Arizona
city: Hot Springs
country: United States
facility: Influence Study Site
state: Arkansas
city: Jonesboro
country: United States
facility: Influence Study Site
state: Arkansas
city: Anaheim
country: United States
facility: Influence Study Site
state: California
city: Fresno
country: United States
facility: Influence Study Site
state: California
city: Garden Grove
country: United States
facility: Influence Study Site
state: California
city: Harbor City
country: United States
facility: Influence Study Site
state: California
city: Huntington Beach
country: United States
facility: Influence Study Site
state: California
city: Lomita
country: United States
facility: Influence Study Site
state: California
city: Long Beach
country: United States
facility: Influence Study Site
state: California
city: Modesto
country: United States
facility: Influence Study Site
state: California
city: Norco
country: United States
facility: Influence Study Site
state: California
city: San Ramon
country: United States
facility: Influence Study Site
state: California
city: Stockton
country: United States
facility: Influence Study Site
state: California
city: Centennial
country: United States
facility: Influence Study Site
state: Colorado
city: Colorado Springs
country: United States
facility: Influence Study Site
state: Colorado
city: Colorado Springs
country: United States
facility: Influence Study Site
state: Colorado
city: Littleton
country: United States
facility: Influence Study Site
state: Colorado
city: Longmont
country: United States
facility: Influence Study Site
state: Colorado
city: Thornton
country: United States
facility: Influence Study Site
state: Colorado
city: Boynton Beach
country: United States
facility: Influence Study Site
state: Florida
city: Coral Gables
country: United States
facility: Influence Study Site
state: Florida
city: Edgewater
country: United States
facility: Influence Study Site
state: Florida
city: Kissimmee
country: United States
facility: Influence Study Site
state: Florida
city: Lauderdale Lakes
country: United States
facility: Influence Study Site
state: Florida
city: Miami
country: United States
facility: Influence Study Site
state: Florida
city: Orlando
country: United States
facility: Influence Study Site
state: Florida
city: Pembroke Pines
country: United States
facility: Influence Study Site
state: Florida
city: Saint Cloud
country: United States
facility: Influence Study Site
state: Florida
city: West Palm Beach
country: United States
facility: Influence Study Site
state: Florida
city: Atlanta
country: United States
facility: Influence Study Site
state: Georgia
city: Canton
country: United States
facility: Influence Study Site
state: Georgia
city: Columbus
country: United States
facility: Influence Study Site
state: Georgia
city: Blackfoot
country: United States
facility: Influence Study Site
state: Idaho
city: Skokie
country: United States
facility: Influence Study Site
state: Illinois
city: Evansville
country: United States
facility: Influence Study Site
state: Indiana
city: Franklin
country: United States
facility: Influence Study Site
state: Indiana
city: Muncie
country: United States
facility: Influence Study Site
state: Indiana
city: Augusta
country: United States
facility: Influence Study Site
state: Kansas
city: Kansas City
country: United States
facility: Influence Study Site
state: Kansas
city: Newton
country: United States
facility: Influence Study Site
state: Kansas
city: Wichita
country: United States
facility: Influence Study Site
state: Kansas
city: Wichita
country: United States
facility: Influence Study Site
state: Kansas
city: Hawesville
country: United States
facility: Influence Study Site
state: Kentucky
city: Madisonville
country: United States
facility: Influence Study Site
state: Kentucky
city: Owensboro
country: United States
facility: Influence Study Site
state: Kentucky
city: Eunice
country: United States
facility: Influence Study Site
state: Louisiana
city: Lafayette
country: United States
facility: Influence Study Site
state: Louisiana
city: Lake Charles
country: United States
facility: Influence Study Site
state: Louisiana
city: Fall River
country: United States
facility: Influence Study Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Influence Study Site
state: Michigan
city: Chelsea
country: United States
facility: Influence Study Site
state: Michigan
city: Essexville
country: United States
facility: Influence Study Site
state: Michigan
city: Niles
country: United States
facility: Influence Study Site
state: Michigan
city: Troy
country: United States
facility: Influence Study Site
state: Michigan
city: Bridgeton
country: United States
facility: Influence Study Site
state: Missouri
city: Fremont
country: United States
facility: Influence Study Site
state: Nebraska
city: Las Vegas
country: United States
facility: Influence Study Site
state: Nevada
city: Las Vegas
country: United States
facility: Influence Study Site
state: Nevada
city: Teaneck
country: United States
facility: Influence Study Site
state: New Jersey
city: Albuquerque
country: United States
facility: Influence Study Site
state: New Mexico
city: Brooklyn
country: United States
facility: Influence Study Site
state: New York
city: Brooklyn
country: United States
facility: Influence Study Site
state: New York
city: Great Neck
country: United States
facility: Influence Study Site
state: New York
city: New York
country: United States
facility: Influence Study Site
state: New York
city: Rochester
country: United States
facility: Influence Study Site
state: New York
city: Westfield
country: United States
facility: Influence Study Site
state: New York
city: Charlotte
country: United States
facility: Influence Study Site
state: North Carolina
city: Charlotte
country: United States
facility: Influence Study Site
state: North Carolina
city: Hickory
country: United States
facility: Influence Study Site
state: North Carolina
city: Mooresville
country: United States
facility: Influence Study Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Influence Study Site
state: North Carolina
city: Columbus
country: United States
facility: Influence Study Site
state: Ohio
city: Dayton
country: United States
facility: Influence Study Site
state: Ohio
city: Groveport
country: United States
facility: Influence Study Site
state: Ohio
city: Lyndhurst
country: United States
facility: Influence Study Site
state: Ohio
city: Middleburg Heights
country: United States
facility: Influence Study Site
state: Ohio
city: Milford
country: United States
facility: Influence Study Site
state: Ohio
city: Willoughby Hills
country: United States
facility: Influence Study Site
state: Ohio
city: Wooster
country: United States
facility: Influence Study Site
state: Ohio
city: Tulsa
country: United States
facility: Influence Study Site
state: Oklahoma
city: Ashland
country: United States
facility: Influence Study Site
state: Oregon
city: Gresham
country: United States
facility: Influence Study Site
state: Oregon
city: Altoona
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Lansdale
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Reading
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Scottdale
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Uniontown
country: United States
facility: Influence Study Site
state: Pennsylvania
city: Warwick
country: United States
facility: Influence Study Site
state: Rhode Island
city: Charleston
country: United States
facility: Influence Study Site
state: South Carolina
city: Rapid City
country: United States
facility: Influence Study Site
state: South Dakota
city: Rapid City
country: United States
facility: Influence Study Site
state: South Dakota
city: Bristol
country: United States
facility: Influence Study Site
state: Tennessee
city: Columbia
country: United States
facility: Influence Study Site
state: Tennessee
city: Elizabethton
country: United States
facility: Influence Study Site
state: Tennessee
city: Franklin
country: United States
facility: Influence Study Site
state: Tennessee
city: Jackson
country: United States
facility: Influence Study Site
state: Tennessee
city: Smyrna
country: United States
facility: Influence Study Site
state: Tennessee
city: Austin
country: United States
facility: Influence Study Site
state: Texas
city: Beaumont
country: United States
facility: Influence Study Site
state: Texas
city: Bryan
country: United States
facility: Influence Study Site
state: Texas
city: Houston
country: United States
facility: Influence Study Site
state: Texas
city: Houston
country: United States
facility: Influence Study Site
state: Texas
city: Irving
country: United States
facility: Influence Study Site
state: Texas
city: Lake Jackson
country: United States
facility: Influence Study Site
state: Texas
city: North Richland Hills
country: United States
facility: Influence Study Site
state: Texas
city: Pharr
country: United States
facility: Influence Study Site
state: Texas
city: Plano
country: United States
facility: Influence Study Site
state: Texas
city: San Antonio
country: United States
facility: Influence Study Site
state: Texas
city: San Antonio
country: United States
facility: Influence Study Site
state: Texas
city: San Antonio
country: United States
facility: Influence Study Site
state: Texas
city: Sugar Land
country: United States
facility: Influence Study Site
state: Texas
city: Waco
country: United States
facility: Influence Study Site
state: Texas
city: Draper
country: United States
facility: Influence Study Site
state: Utah
city: Magna
country: United States
facility: Influence Study Site
state: Utah
city: Orem
country: United States
facility: Influence Study Site
state: Utah
city: Salt Lake City
country: United States
facility: Influence Study Site
state: Utah
city: Alexandria
country: United States
facility: Influence Study Site
state: Virginia
city: Ashburn
country: United States
facility: Influence Study Site
state: Virginia
city: Charlottesville
country: United States
facility: Influence Study Site
state: Virginia
city: Gainesville
country: United States
facility: Influence Study Site
state: Virginia
city: Midlothian
country: United States
facility: Influence Study Site
state: Virginia
city: Norfolk
country: United States
facility: Influence Study Site
state: Virginia
city: Virginia Beach
country: United States
facility: Influence Study Site
state: Virginia
city: Port Orchard
country: United States
facility: Influence Study Site
state: Washington
city: Spokane
country: United States
facility: Influence Study Site
state: Washington
city: Spokane
country: United States
facility: Influence Study Site
state: Washington
city: La Crosse
country: United States
facility: Influence Study Site
state: Wisconsin
city: Cardiff
country: Australia
facility: Influence Study Site
state: New South Wales
city: Castle Hill
country: Australia
facility: Influence Study Site
state: New South Wales
city: Darlinghurst
country: Australia
facility: Influence Study Site
state: New South Wales
city: Westmead, Sydney
country: Australia
facility: Influence Study Site
state: New South Wales
city: Chermside
country: Australia
facility: Influence Study Site
state: Queensland
city: Sherwood
country: Australia
facility: Influence Study Site
state: Queensland
city: Daw Park
country: Australia
facility: Influence Study Site
state: South Australia
city: Clayton
country: Australia
facility: Influence Study Site
state: Victoria
city: Fitzroy North
country: Australia
facility: Influence Study Site
state: Victoria
city: Prahran
country: Australia
facility: Influence Study Site
state: Victoria
city: Nedlands
country: Australia
facility: Influence Study SIte
state: Western Australia
city: Antwerpen
country: Belgium
facility: Influence Study Site
city: Coquitlam
country: Canada
facility: Influence Study Site
state: British Columbia
city: Langley
country: Canada
facility: Influence Study Site
state: British Columbia
city: Surrey
country: Canada
facility: Influence Study Site
state: British Columbia
city: Brampton
country: Canada
facility: Influence Study Site
state: Ontario
city: London
country: Canada
facility: Influence Study Site
state: Ontario
city: Niagara Falls
country: Canada
facility: Influence Study Site
state: Ontario
city: Sarnia
country: Canada
facility: Influence Study Site
state: Ontario
city: Toronto
country: Canada
facility: Influence Study Site
state: Ontario
city: Toronto
country: Canada
facility: Influence Study Site
state: Ontario
city: Mirabel
country: Canada
facility: Influence Study Site
state: Quebec
city: Montreal
country: Canada
facility: Influence Study Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Influence Study Site
state: Quebec
city: Birkenhead
country: New Zealand
facility: Influence Study Site
state: Auckland
city: Grafton
country: New Zealand
facility: Influence Study Site
state: Auckland
city: Remuera
country: New Zealand
facility: Influence Study Site
state: Auckland
city: Rotorua
country: New Zealand
facility: Influence Study Site
state: Bay Of Plenty
city: Tauranga
country: New Zealand
facility: Influence Study Site
state: Bay Of Plenty
city: Beckenham
country: New Zealand
facility: Influence Study Site
state: Christchurch
city: Christchurch Central
country: New Zealand
facility: Influence Study Site
state: Christchurch
Study officials:
affiliation: Romark Laboratories L.C.
name: Jean-Francois Rossignol, M.D., Ph.D.
role: STUDY_DIRECTOR
References: